title: Inhibiting intracellular CD28 in cancer cells enhances antitumor immunity and overcomes anti- PD-1 resistance via targeting PD-L1

first: Zhen

last: Yang

summary: In vivo genome-wide CRISPR screening unraveled the non-classical role of cancer cell Cd28 in tumor immune escape, and identified cancer cell Cd28 as a novel target in breast cancer immunotherapy by modulating tumor immunogenicity and anti-tumor CD8+ T cell responses.

overall_design: 4T1 cells infected by mGeCKO library lentivirus were orthotopically inoculated into Six-to-ten-week-old female BALB/c. Single-cell RNA seqencing (Chromium, 10X Genomics) was performed to compare the tumor-infiltrting immune cells (sorted by Fluorescence-activated cell sorting) between sgNC and sgRNA infected tumors on day 6, 8, 10 after tumor implantation.

first: Xinpeng

last: Liu

first: Xuetao

last: Cao


title: Inhibiting intracellular CD28 in cancer cells enhances antitumor immunity and overcomes anti-PD-1 resistance via targeting PD-L1

status: Public on Dec 26 2024

city: Tianjin

address: Weijin Street

country: China

institute: Nankai University

type: Expression profiling by high throughput sequencing

overall_design: Cd28+/+ and Cd28-/- 4T1 cells were orthotopically inoculated into Six-to-ten-week-old female BALB/c. Single-cell RNA seqencing (Chromium, 10X Genomics) was performed to compare the tumor-infiltrting immune cells (sorted by Fluorescence-activated cell sorting) between NC and Cd28 KO tumors on day 6, 10 after tumor implantation.


title: A bipolar disorder-associated missense variant alters adenylyl cyclase 2 activity and promotes mania-like behavior

city: Munich

first: Jan

middle: M

last: Deussing

address: Kraepelinstr. 2-10

country: Germany

institute: Max Planck Institute of Psychiatry

summary: The single nucleotide polymorphism rs13166360, causing a substitution of valine 147 to leucine in the adenylyl cyclase 2 (ADCY2), has previously been associated with bipolar disorder (BD). Here we show that this missense mutation diminishes ADCY2 activity by altering its subcellular localization. Mice homozygous for the leucine variant display signs of a mania-like state accompanied by cognitive impairments. Mutant mice are hypersensitive to amphetamine and mania-like behaviors are responsive to lithium treatment. Exposure to chronic social defeat stress switches homozygous leucine variant carriers from a mania- to a depressive-like state. Single-cell RNA-seq revealed widespread expression of ADCY2 in numerous hippocampal cell types. Differentially expressed genes particularly identified from glutamatergic CA1 neurons point towards ADCY2 variant-dependent alterations in multiple biological processes including cAMP-related signaling pathways. These results validate ADCY2 as a BD risk gene providing insights into underlying disease mechanisms potentially opening novel avenues for therapeutic intervention strategies.

overall_design: Single-cell RNA sequencing of ventral hippocampus of wild-type (ADCY2-V151) and mutant (ADCY2-L151) ADCY2 mice.

first: Paromita

last: Sen


title: Gene expression associated with endocrine therapy resistance in estrogen receptor-positive breast cancer

status: Public on Dec 25 2024

city: Duarte

first: Yate-Ching

last: Yuan

state: CA

address: 1500 East Duarte

country: USA

institute: City of Hope

summary: Gene expression analysis to study early-stage estrogen receptor-positive breast cancer patient associated with endocrine therapy resistance.

overall_design: Breast cancer primary cancer patients were treated with endocrine therapy, including selective estrogen receptor modulators (SERMs), selective estrogen receptor degraders (SERDs), and aromatase inhibitors (AI) with both locoregional and distant recurrences with IRB approval were selected for this study. Surgical pathology archives were queried for HER2- ER+BC formalin-fixed paraffin-embedded (FFPE) specimens resected with a ER+ more than 10% as cutoff. mRNAseq gene expression analysis for 48 patient by  exploring recurrent vs non-recurrent (NR) groups using a nCounter® Custom CodeSet by NanoString.

first: Veronica

last: Jones

first: Hongwei

middle: H

last: Yin

first: Yongzhe

last: Wang

first: Sierra

last: Li

first: Dana

last: Aljaber

first: Angelica

last: Sanchez

first: Christine

last: Quinones

first: Dan

last: Schmolze

first: Yuan

first: Joanne

last: Mortimer

first: Lisa

last: Yee

first: Laura

last: Kruper

first: Tijana

last: Jovanovic-Talisman

first: Jerneja

last: Tomsic

first: Nancy

first: Tanya

last: Chavez

first: Ruth

last: O’Regan

first: Qamar

middle: J

last: Khan

first: Melissa

last: Davis

first: Kevin

last: Kalinsky

first: Jane

last: Meisel

first: Rick

last: Kittles

first: Lorna

last: Rodriguez-Rodriguez

first: Victoria

last: Seewaldt


title: Differential control of growth and identity by HNF4α isoforms in pancreatic ductal adenocarcinoma [HiChIP]

city: Salt Lake City

first: Eric

middle: L

last: Snyder

state: Utah

address: 2000 Cir of Hope Dr

department: Oncological Sciences

institute: University of Utah

summary: Although transcriptomic studies have stratified pancreatic ductal adenocarcinoma (PDAC) into clinically relevant subtypes, classical or basal-like, further research is needed to identify the transcriptional regulators of each subtype. Previous studies identified HNF4α as a key regulator of the classical subtype, but the distinct contributions of its isoforms (P1 and P2), which display dichotomous functions in normal development and gastrointestinal malignancies, remain unexplored. Here we show that HNF4α-positive human PDAC tumors exhibit uniform expression of P2-isoforms but variable expression of P1 isoforms. To dissect the roles of each isoform in PDAC, we performed functional, transcriptomic, and epigenetic analysis after exogenous expression in HNF4α-negative models or CRISPRi-mediated knockdown of endogenous isoforms. We demonstrated that P1 isoforms are less compatible with growth and stronger transcriptional regulators than P2. Despite both isoforms sharing a common DNA binding domain, P1 isoforms displayed stronger binding at HNF4α target genes, resulting in increased transcriptional activity. These findings provide a detailed characterization of HNF4α P1 and P2 isoforms and their distinct roles in PDAC biology.

overall_design: H3K27ac HiChIP was performed on ASPC1 after CRISPRi to inhibit expression of HNF4α P1, P2, or both isoforms.

first: Pengshu

last: Fang

first: Emily

last: Wilson

first: Xiaoyang

last: Zhang


title: CHD4 remodels cellular chromatin accessibility and activates c-Myc pathway via phase separation in multiple myeloma

city: Nanjing

first: Pinggang

last: Ding

address: 138 Xianlin Road

department: School of Medicine

institute: Nanjing University of Chinese Medicine

summary: Multiple myeloma (MM) is an incurable hematologic malignancy, which is inherently related to chromatin abnormalities. Chromatin remodeling factors play an important role in the regulation of chromatin abnormalities, among which chromodomain-helicase-DNA-binding protein 4 (CHD4) was positive-associated with poor outcomes in MM patients and an elevated level of CHD4 promoted MM cell proliferation. Mechanistically, CHD4 untwisted c-Myc G4 and regulated chromatin accessibility through ATPase domain. Additionally, CHD4 recruited c-Myc though chromatin domain and stabilized c-Myc to chromatin by liquid–liquid phase separation, which up-regulated the expression of c-Myc. Furthermore, Luteolin 7-O-glucuronide and Idarubicin were identified as potential drugs targeting ATPase domain and chromatin domain for MM by a de novo design. Our study highlights the role of CHD4 as a high-risk gene in MM and suggests that remodels cellular chromatin accessibility and activates c-Myc pathway via phase separation in MM.

overall_design: RNA-sequencing (mRNA-seq) to determine the changes of transcription factor expression in MM Ctrl and CHD4-KD cells and found that the knockdown of CHD4 down-regulated the expression


title: Baicalin alleviates lipid accumulation in adipocytes via inducing metabolic reprogramming and targeting Adenosine A1 receptor

city: Chongqing

first: Zaikuan

state: province

address: The Ministry of Education Key Laboratory of Laboratory Medical Diagnostics

institute: Chongqing Medical University

summary: Excessive lipid accumulation can lead to obesity, metabolic-associated fatty liver disease, and type 2 diabetes. However, there are currently few drugs that could effectively and safely inhibit the accumulation of intracellular lipid. In this study, we observed that baicalin significantly altered cellular respiration by reducing mitochondrial oxygen consumption while enhancing glycolytic flux, accompanied by increased phosphorylation of AMPK and ACC, suggesting an adaptation to altered energy availability. Baicalin effectively reduced lipid droplet formation and intracellular triglyceride levels in adipocytes, as marked by downregulating genes and proteins associated with lipid storage, including Cd36, Fabp4, and FASN. Transcriptomic analysis identified 2,150 differentially expressed genes in baicalin-treated adipocytes, with significant enrichment in metabolic pathways such as glycolysis, gluconeogenesis, and lipid metabolism. Further analysis revealed that baicalin upregulated glycolytic and fatty acid β-oxidation (FAO) pathways while downregulating pyruvate dehydrogenase, inducing a shift toward glycolysis and FAO for energy production. Molecular docking analysis revealed that adenosine A1 receptor (ADORA1) was the target of baicalin, which inhibited the maturation of sterol regulatory element binding protein 1 (SREBP1) and finally alleviated lipid deposition. These results demonstrate that baicalin induces metabolic reprogramming of adipocytes by inhibiting glucose aerobic metabolism while enhancing anaerobic glycolysis and FAO. Meanwhile, baicalin targets ADORA1, which subsequently influences the processing of SREBP1 and downregulates lipid biosynthesis, positioning baicalin as a potential therapeutic agent against obesity and related metabolic disorders.

overall_design: RNA sequencing data of adipocytes treated or not treated with 200μM baicalin.  featureCounts v1.5.0-p3 was used to count the reads numbers mapped to each gene.And then FPKM of each gene was calculated based on the length of the gene and reads count mapped to this gene. FPKM, expected number of Fragments Per Kilobase of transcript sequence per Millions base pairs sequenced, considers the effect of sequencing depth and gene length for the reads count at the same time, and is currently the most commonly used method for estimating gene expression levels.

first: Runzhi

last: Wang

first: Jin

last: Cai

first: Xinyi

last: Li

first: Xiaosong

last: Feng

first: Shengming

last: Xu

first: Zhihong

last: Jiang

first: Peiyi

last: Lin

first: Zengyi

last: Huang

first: Yajun

last: Xie


title: Differential control of growth and identity by HNF4α isoforms in pancreatic ductal adenocarcinoma [ChIP-Seq]

type: Genome binding/occupancy profiling by high throughput sequencing

overall_design: ChIPSeq was performed on human PDAC cell lines after genetic manipulation of HNF4α. BxPC3 and Panc10.05 was treated with doxycycline to induce expression of HNF4α P1 and P2 isoforms. CRISPRi was used to inhibit expression of HNF4α P1, P2, or both isoforms.


title: Differential control of growth and identity by HNF4α isoforms in pancreatic ductal adenocarcinoma

summary: This SuperSeries is composed of the SubSeries listed below.

overall_design: Refer to individual Series


title: miRNA expression in the exosomes from oxaliplatin treated or not sw480 cells

first: Gu

last: Yuanyuan

state: Jiangsu

address: 163 Xianlin Road

department: School of Life Sciences

institute: Nanjing University

summary: detect miRNA expression in the exosomes isolating from the cell culture of sw480 cells treated by oxaliplatin or not

platform_organism:
Homo sapiens
Mus musculus
Rattus norvegicus

overall_design: In this study, 20μM oxaliplatin was used to treat sw480 cells for 48h. Then the culture medium of treated cells and control cells were collected. Exosomes were isolated and microarray was used to detect the different miRNA expression in exosomes.

first: Yuanyuan

last: Gu


title: A circRNA-mRNA pairing mechanism regulates tumor growth and endocrine therapy resistance in ER-positive breast cancer

city: xiamen

first: ruichao

last: nie

state: 福建Fujian

address: xiangshanlu

institute: xiamen university

summary: The molecular mechanisms underlying estrogen receptor (ER)-positive breast carcinogenesis and drug resistance remain incompletely understood. Elevated expression of CCND1 is linked to enhanced invasiveness, poorer prognosis, and resistance to drug therapies in ER-positive breast cancer. In this study, we report that a highly expressed circular RNA (circRNA) derived from FOXK2, called circFOXK2, stabilizes CCND1 mRNA, thereby promoting cell cycle progression, cell growth, and endocrine therapy resistance in ER-positive breast cancer cells. Mechanistically, circFOXK2 binds directly to CCND1 mRNA via RNA-RNA pairing, recruiting the RNA-binding protein ELAVL1/HuR to stabilize CCND1 mRNA, thereby increasing CCND1 protein levels. Elevated CCND1 activates the CCND1-CDK4/6-p-RB-E2F signaling axis, driving the transcription of downstream E2F target genes and promoting the G1/S transition during cell cycle progression. Consequently, anti-sense oligonucleotide (ASO)-targeting circFOXK2 (ASO-circFOXK2) suppresses the growth of ER-positive breast cancer cells both in vitro and in vivo. Combination treatment with ASO-circFOXK2 and Tamoxifen shows synergistic effects. Moreover, ASO-circFOXK2 restores Tamoxifen sensitivity in Tamoxifen-resistant ER-positive breast cancer cells both in vitro and in vivo. The clinical relevance is underscored by the high expression of circFOXK2, which is positively correlated with that CCND1 expression in ER-positive breast cancer cell lines and clinical tumor tissues. Overall, our findings reveal the critical role of circFOXK2 in stabilizing the mRNA of the oncogene CCND1 and promoting cell cycle progression, identifying circFOXK2 as a potential therapeutic target for treating ER-positive breast cancer in clinical settings.

overall_design: RNA-seq performed in this study was designed to understand the molecular mechanisms underlying circFOXK2 in gene transcriptional regulation.

first: Wen

last: Liu

first: Jia

last: Yi

first: Rui-chao

last: Nie


title: An engineered mycobacterium smegmatis expressing anti-PD-L1/IL-15 immunocytokine induces and activates specific antitumor immunity

first: Mei

address: 321 Zhongshan Road

institute: Nanjing Drum Tower Hospital

summary: Immune checkpoint inhibitors and cytokines have revolutionized tumor treatment but are still limited by dose-dependent toxicity and efficacy. In situ vaccine platforms based on intelligent microbes are promising therapeutic strategies, which can sustainably deliver drugs locally without causing severe systemic risks. Here,  we have innovatively engineered a nonpathogenic, adjuvant-acting Mycobacterium smegmatis (M. smegmatis) that coexpresses a PD-L1 inhibitor and an IL-15 cytokine complex containing the IL-15Rα sushi domain (Ms-PDL1scfv-IL15). We demonstrate that PD-L1 inhibitor and IL-15 secretion systemically binds mouse or human PD-L1 and maintains IL-15 stimulatory activity. The bifunctional Ms-PDL1scfv-IL15 overcomes resistance to PD-L1 blockade, recruits numerous immune cells in situ, induces dendritic cells (DCs) maturation, initiates the M1 anti-tumor polarization of macrophages, increases the proliferation and activation of NK cells and tumor-infiltrating CD8+ T cells, inhibits the Tregs, elicits abscopal effects, stimulates rapid tumor regression, prevents metastasis, and leads to long-term survival in several syngeneic tumor mouse models. We also found that the combination of Ms-PDL1scfv-IL15 with GM–CSF synergistically stunted the tumor progress and stasis. Moreover, intratumoral administration of Ms-PDL1scfv-IL15 can capture tumor antigen fragments, and boost DCs presentation of antigens, which remarkably initiates tumor antigen-specific immune response, leading to durable tumor regression and specific antitumor immunity. In summary, this engineered M. smegmatis to recruit and activate innate and adaptive antitumor immune responses, offering a potent cancer immunotherapy strategy to treat patients with cold tumors or resistance to checkpoint blockade.

overall_design: To further explore the molecular mechanisms underlying Ms-PDL1scfv-IL15 which induce long-term and specific anti-tumor protection, we performed bioinformatics analysis of mRNA transcriptomes towards Ms-PDL1scfv-IL15 treated tumor

first: Yi

last: Mei

first: Junmeng

last: Zhu

first: Jie

last: Shao

first: Baorui


title: Differential control of growth and identity by HNF4α isoforms in pancreatic ductal adenocarcinoma [RNA-Seq]

first: Eric

last: Snyder

overall_design: RNASeq was performed on human PDAC cell lines after genetic manipulation of HNF4α. BxPC3 and Panc10.05 was treated with doxycycline to induce expression of HNF4α P1 and P2 isoforms. CRISPRi was used to inhibit expression of HNF4α P1, P2, or both isoforms.

first: Pengshu

last: Fang


title: Unveiling Multi-Omics and Immune Landscapes in COVID-19 Patients' Ovaries Microenvironment for Oocyte Competency Biomarkers Identification

city: Jinan

first: Chen

last: Geng

state: State...

address: Shandong Provincial Clinical Medicine Research Center for reproductive health

institute: Shandong University

summary: Background: The outbreak of coronavirus disease 2019 (COVID-19) poses a considerable health threat to humanity, with potential implications for the ovarian microenvironment remaining uncertain. Methods: Transcriptomic and proteomic analyses of ovarian granulosa cells, along with metabolomic and lipidomic profiling of follicular fluid, were conducted on 17 non-COVID-19 cases and 9 COVID-19 cases. This study received approval from the ethics committee (KYLL-2022-581). Generalized estimating equations model was performed to identify oocyte competency biomarkers. Additionally, cell proliferation, apoptosis, and altered pathways were examined following lentivirus transfection. Methods: Transcriptomic and proteomic analyses of ovarian granulosa cells, along with metabolomic and lipidomic profiling of follicular fluid, were conducted on 17 non-COVID-19 cases and 9 COVID-19 cases. This study received approval from the ethics committee (KYLL-2022-581). Generalized estimating equations model was performed to identify oocyte competency biomarkers. Additionally, cell proliferation, apoptosis, and altered pathways were examined following lentivirus transfection. Conclusions: By integrating untargeted metabolomic and lipidomic features, we identified biomarkers indicative of oocyte competency influenced by COVID-19.

overall_design: To investigate the influence of COVID-19 on ovarian granulosa cells, transcriptomic analyses of ovarian granulosa cells were conducted on 17 non-COVID-19 cases and 9 COVID-19 cases.

first: Linlin

last: Cui

first: Min

last: Zhang

last: Li


title: Acetyl-CoA metabolism determines the partitioning of lipids between adipose tissue and skin [RNA-seq 2]

city: Philadelphia

first: Kathryn

last: Wellen

state: PA

address: 421 Curie Blvd

department: Dermatology

institute: University of Pennsylvania

summary: ATP-citrate lyase (ACLY) generates cytosolic acetyl-CoA for lipid synthesis and is a promising therapeutic target in disease contexts with altered lipid metabolism. Here, we developed inducible whole-body Acly knockout mice to determine the requirement for ACLY in normal tissue functions, uncovering its crucial role in skin homeostasis and barrier function. ACLY-deficient skin upregulates the acetyl-CoA synthetase ACSS2; and skin-specific double knockout (DKO) of Acly and Acss2 exacerbates skin abnormalities, with differential effects on two major lipid-producing skin compartments. While the epidermis is depleted of key barrier lipids, the sebaceous glands unexpectedly increase their lipid-rich sebum secretion, supplied in part by fatty acids released from adipose tissues. Accordingly, DKO mice rapidly lose fat mass, and dietary lipid supplementation partially rescues both the lipoatrophy and aberrant skin phenotypes. Thymic stromal lymphopoietin (TSLP), a cytokine with a role in regulating sebaceous glands, is overexpressed in DKO epidermis and thus may stimulate sebum secretion in response to deficient epidermal acetyl-CoA synthesis. Together, the data demonstrate that cytosolic acetyl-CoA synthesis in the skin both maintains local tissue homeostasis and influences systemic lipid partitioning and storage.

overall_design: ACLY and ACSS2 was deleted across whole body tissues of the mice, under UBC-CreERT2 promoter. Epidermis was harvested at 12 days and 21 days post-tamoxifen induction

first: Phuong

middle: T

last: Nguyen

first: Mia

last: Shiue

first: Nina

last: Kuprasertkul

first: Pedro

last: Costa-Pinheiro

first: Luke

last: Izzo

first: Hayley

middle: A

last: Affronti

first: Laura

middle: V

last: Pinheiro

first: Shivani

last: Ghaisas

first: Joyce

middle: Y

first: Peining

last: Xu

first: Jordan

middle: C

last: Harris

first: Charles

middle: W

last: Bradley

first: John

last: Seykora

first: Xiaolu

last: Yang

first: Taku

last: Kambayashi

first: Clementina

last: Mesaros

first: Brian

last: Capell

middle: E


title: Acetyl-CoA metabolism determines the partitioning of lipids between adipose tissue and skin

first: Kathryn

last: Wellen


title: Cyclin-dependent kinase inhibitors sequentially determine the neural-glial lineage boundaries in the developing cortex

city: Seoul

first: Tae-Young

last: Roh

state: --- Select One ---

address: 52 Ewhayeodae-gil, Seodaemun-gu

department: Life Sciences

country: South Korea

institute: Ewha Womans University

summary: Neural stem cells (NSCs) can generate neurons and glia, but the regulatory mechanisms to invoke different lineages are largely unclear. Here, we addressed the role of cyclin-dependent kinase inhibitors (CDKIs) in the later stage of embryonic brain development. We found upregulations of p18 and p27 among CDKIs at the onset of astrocyte generation. Acute manipulation of p18 and p27 expressions in vivo revealed that the level of CDKIs at the transitional stage regulates the lineage switching between neurons and astrocytes. We generated a conditional knock-in mouse to induce p18 in NSCs. The transcriptome of micro-dissected tissue showed the enhanced activities of glial cell development and delta-notch signaling by the increased p18. Furthermore, Dlx2 induced olfactory bulb interneuron from multipotent intermediate cells with reduction of astrocyte in the late embryonic stage. Together, our results demonstrated the function of CDKIs in sequentially determining the boundary among different cellular lineages in the brain.

overall_design: To identify functional link between the CDKIs and the neural to astrocytic differentiation switching, we generated a conditional knock-in mouse containing a loxP-flanked stop sequence and p18-P2A-mKO2 in the ROSA26 locus.

first: Wonyoung

last: Lee

first: Byunghee

last: Kang

first: Yoichi

last: Kosodo


title: Acetyl-CoA metabolism determines the partitioning of lipids between adipose tissue and skin [RNA-seq 1]

overall_design: ACLY was deleted across whole body tissues of the mice, under UBC-CreERT2 promoter. Epidermis was harvested

first: Phuong

last: Nguyen

first: Mia

last: Shiue

first: Nina

last: Kuprasertkul

first: Pedro

last: Costa-Pinheiro

first: Luke

last: Izzo

first: Hayley

last: Liu


title: Chromatin site specific accessibility: a microtopography regulated door into the stem cell fate [ATAC-seq]

city: Hangzhou

first: HONGWEI

last: OUYANG

state: Zhejiang

address: 866 Yu Hang Tang Road,Hangzhou, Zhejiang, P.R.China.

institute: Zhejiang University

summary: Biomaterials engineered to mimic extracellular matrix (ECM) topography play a pivotal role in tissue engineering. Previous research indicates that certain  biomimetic topographies can guide stem cells towards multiple specific lineages. However, the mechanisms by which these topographic cues prime the multilineage differentiation remain largely elusive. In this study, we show that topography influences nuclear tension in MSCs through a mechanotransductive feedback mechanism, which in turn reshapes chromatin accessibility patterns, finally determines the stem cell lineage commitment. When cultured on an aligned substrate, MSCs show high cytoskeletal tension along the fibre direction, resulting in anisotropic nucleus tensile stress. This further leads to the opening of chromatin sites related to neurogenic, myogenic, and tenogenic genes by the regulation of transcription factors such as TLX. On the other hand, when MSCs are lied on a random substrate, they experience isotropic nucleus stress, leading to the opening of chromatin sites related to osteogenic and chondrogenic genes through the regulation of RUNX family transcription factors. Collectively, our results show that aligned and random topography induce site specific chromatin stretching and lineage specific gene expressing in MSCs, leading to their priming for specific lineages. Our study thus proposes a novel concept for topographic cues influencing on cell behavior and fate during tissue reconstitution and regeneration.

overall_design: The experiment was divided into 3 groups, which were untreated control group, aligned scaffold group and random scaffold group. Hi-C and ATAC-seq were performed on the cells of these three groups.

first: Hongwei

last: Ouyang

first: Wenyan

last: Zhou

first: Junxin

last: Lin

first: Qianchun

last: Wang


title: IFI16-mediated cellular senescence drives HMOX1-dependent evasion of ferroptosis and radioresistance in glioblastoma

city: Shanghai

first: Zhou

last: Yuchuan

address: No.2094 Xie-Tu Road

department: Institute of Radiation Medicine

institute: Fudan University

summary: Glioblastoma multiforme (GBM) is a persistent challenge in oncology due to its aggressive nature and limited survival. Despite various therapeutic strategies, the recurrence of GBM still exists, driven by the complex cellular diversity and evolutionary dynamics during the treatment process. This study established a radioresistant GBM cell model through repeated exposure to ionizing radiation and revealed a distinct manifestation of cellular senescence of these cells. The comprehensive genomic and transcriptomic analyses identified that IFI16, as a critical driver of cellular senescence, contributed to the radioresistance of GBM. Mechanistically, IFI16 was involved in orchestrating HMOX1 transcription thereby attenuating ferroptosis after irradiation. HMOX1 limited lipid peroxidation, reactive oxygen species (ROS) production, and intracellular Fe2+ content following irradiation, thus effectively counteracting ferroptosis in GBM. Furthermore, IFI16 interacted with the transcription factors JUND and SP1 through its pyrin domain, robustly facilitating HMOX1 expression, further inhibiting ferroptosis and enhancing radioresistance in GBM cells. Notably, glyburide, an anti-aging agent, effectively disrupted IFI16 function and thus enhanced ferroptosis and radiosensitivity. By specifically targeting the pyrin domain of IFI16, glyburide emerged as a potential therapeutic agent against GBM radioresistance. In conclusion, these novel findings underscored the central role of IFI16 in GBM radioresistance and offered promising avenues for innovative therapeutic interventions against GBM radiosensitivity

overall_design: To investigate the function of the IFI16 gene in radioresistance in GBM cells, we established U251MG radioresistant cell lines in which IFI16 was knocked down by shRNA.

first: Yuchuan

first: Chunlin

last: Shao

first: Jianghong

last: Zhang

first: Yan

last: Pan


title: A Single Cell Perspective of the Effects of Dopamine in the Regulation of HIV Latency Phenotypes in a Myeloid Cell Model

city: San Diego

first: Maria

middle: Cecilia

last: Marcondes

address: 3525 John Hopkins Ct. #200

institute: San Diego Biomedical Research Institute

summary: The promonocytic cell line U1, which contains the HIV-1 proviral sequence, and its parent uninfected promocytic cell line U937, were incubated with Dopamine 10uM or with 1 uM of the dopamine-induced Monocyte Related Protein (MRP) 8/14. The cells were stimulated for 24 hrs and then harvested for a 10X Genomics single cell approach for the detection of transcriptional patterns associated with viral replication phenotypes.

overall_design: U1 or U937 cells were plated at 10^6/ml in 6 well plates and then stimulated with Dopamine or selective agonists for 24hrs. The experiments were performed in biological and technical replicates.

first: Marcondes

last: Maria Cecilia Garibaldi

first: Basova

last: Liana

first: Fox

last: Howard


title: Chromatin site specific accessibility: a microtopography regulated door into the stem cell fate [Hi-C]


title: Menin orchestrates macrophage reprogramming to maintain the pulmonary immune homeostasis

city: Xiamen

first: Bin

last: Xu

address: Room 112, Chengzhi building, School of Medicine, Xiamen University, Xiang'an South Road, Xiang'an District

institute: Xiamen University

summary: The potential importance of menin in immune regulation remains unclear. Here, we report that myeloid deletion of Men1 results in the development of spontaneous pulmonary alveolar proteinosis (PAP). This is strongly correlated with impaired development of alveolar macrophages (AM) and epigenetic inactivation of the GM-CSF pathway caused by Men1 deficiency. Mechanistically, menin directly interacts with SETD2 and collectively maintain GM-CSF expression through H3K36me3, which orchestrates AM reprogramming and pulmonary immune homeostasis.

overall_design: Stimulation of BM-derived monocytes with M-CSF induced differentiation into pre-macrophages (BMDMs, M0). BMDM cells from WT(Men1f/f )and KO(Men1∆M/∆M) mice were harvested for ChIP-seq to determine the landscapes of menin, SETD2, H3K36me3 and H3K4me3 on chromatin

first: XingWen

last: Zhu

first: GuangHui

last: Jin


title: MPO and TRH within leukemia stem cells increased chemosensitivity in acute myeloid leukemia

city: Taipei

first: Chung-Hsing

last: Chen

address: No.1 Ai-Guo West Road

department: Department of Mathematics

country: Taiwan

institute: University of Taipei

summary: The "7+3" regimen is widely recognized as the established standard induction therapy for newly diagnosed acute myeloid leukemia (AML), exhibiting a complete remission (CR) rate of 70%. By employing single-cell RNA sequencing (scRNA-seq), we meticulously examined the cellular states of bone marrow mononuclear cells from AML patients at the time of diagnosis and identified leukemia stem cells (LSCs) among these cells. The genetic profiles of the LSCs were subsequently compared between the CR and non-CR groups and further validated using independent cohorts. The non-CR AML patients exhibited a significant increase in the proportion of immature cells during hematopoiesis within the AML cell populations. Moreover, we found that expressions of MPO (log2 fold-change = 0.89; adjusted p <0.0001) and TRH (log2 fold-change = 0.65; adjusted p <0.0001) within LSCs were significantly higher in the CR than non-CR groups, which were further validated by independent cohorts. Furthermore, patients with higher expression of TRH and MPO demonstrated substantially improved relapse-free survival (p = 0.009 for TRH; p = 0.002 for MPO) and overall survival (p < 0.001 for TRH; p = 0.002 for MPO). The dysregulation of the OXPHOS pathway, along with altered interferon alpha and gamma responses, disrupted cholesterol homeostasis, and aberrant MYC activity, may contribute as underlying mechanisms for the observed association between MPO or TRH and chemotherapy response.

overall_design:
The bone marrow samples were collected from 20 consecutive de novo AML patients who underwent "7+3" or "7+3"-like induction therapy. These patients were categorized into two groups based on their bone marrow status assessed approximately 28 days after the induction chemotherapy: complete remission (CR) group (n = 15) and non-complete remission (non-CR) group (n = 5). Clinical features of the patients were provided in Supplemental Table 1 in our manuscript. The processed data that can accelerate reproducible single-cell analysis is available from Single Cell Portal under accession SCP2316 (https://singlecell.broadinstitute.org/single_cell/study/SCP2316). However, the raw data is not available due to patient privacy concerns.

>>>Submitter states: The raw data is not available due to patient privacy concerns<<<

first: C

first: T

last: Hsiao

last: Teng


title: Dsk1 repairs DSBs by homologous recombination via Rad52 in  Schizosaccharomyces pombe

city: nanjing

first: Guangchun

last: Lu

address: wenyuan road

institute: Nanjing Normal University

summary: To investigate the different of gene expression between dsk1Δ and wild strain, and then, we performed the gene expression analysis from the RNA-Seq data.

overall_design: Gene expression analysis of the  dsk1Δ mutant strain was compared with the wild-type.

first: Gang

last: Feng


title: Detection of occurrent somatic hypermutation and associated gene expression profile in single B cells

city: Punta Arenas

first: Julieta

last: Sepulveda Yanez

state: Magallanes Region

address: Av. Bulnes

country: Chile

institute: University of Magallanes

summary: This study provided new insights into the molecular mechanisms of SHM. For the first time, SHM was detected at the single-cell level in 58% of FL samples but not in chronic lymphocytic leukemia (CLL) used as control. The occurrence of SHM at the single-cell level was correlated with higher expression of DNA repair pathways and activation-induced cytidine deaminase (AID), as well as the motifs associated with AID. FL is an essential in vivo model for studying SHM due to its high rate of ongoing SHM, and the findings of this study contribute to our understanding of the molecular mechanisms involved in human B-cells.

overall_design: 10X Genomics of flowcytometry-purified Follicular Lymphoma cells, 5' chemistry, full transcriptome and BCR enrichment

last: Sepulveda-Yanez

first: Cornelis

last: van Bergen

first: Hendrik

last: Veelken


title: Omega-3 PUFAs Slow Organ Aging through Promoting Energy Metabolism

city: guangzhou

first: yabing

last: xiong

address: 1838 North Guangzhou Avenue

institute: southern medical university

summary: Energy metabolism dysfunction is highly connected with aging. Aged mice could exhibit multiple energy metabolism disorders, such as insulin resistance, inhibition of fatty acid degradation and lipid accumulation. PPARα is a key transcriptional factor regulating genes of fatty acid β-oxidation, playing a crucial role in lipid metabolism and ATP production. However, the role of PPARα in retarding organ aging has not been fully elucidated. Herein, we investigated the beneficial effects of Omega-3 PUFAs, endogenous agonists of PPARα, in naturally aging mice, accelerated aging mice as well as several kinds of cells cultures. Moreover, we performed studies in mfat-1 transgenic mice at 24 months of age to explore the anti-aging effects of Omega-3 PUFAs. We found that Omega-3 PUFAs and fat-1 gene restored fatty acid β-oxidation and ATP production, reduced lipid accumulation, inhibited age-related pathological changes, preserved organ functions to delay aging process. Our results suggest Omega-3 PUFAs is a promising therapeutic approach to promote healthy aging in the elderly.

overall_design: We performed transcriptomics sequencing analysis of kidney to further the beneficial effects of fat-1 gene in 24-month-old mice.

first: Yabing

last: Xiong


title: The function of Men1 gene in macrophage

summary: To explore the target genes of Men1 in macrophage, we isolated the peritoneal cavity macrophage from WT and Men1 knockout mouse and performed gene expression profiling analysis by RNA-seq.

overall_design: Comparative gene expression profiling analysis between WT and Men1 knockout(KO) peritoneal cavity macrophage, which is stimulated by thioglycollate broth.

first: Gaung-Hui


title: Bulk transcriptomic profiling of dermal macrophage subtypes

city: Osaka

first: Yu-Tung

last: Li

address: 2-2 Yamada-oka, Suita

country: Japan

institute: Osaka University

summary: Viable mouse dermal macrophage (CD45+F4/80+SiglecF-) subtypes were identified by antigen expression combination of Ly6C, FRb and CD163 and sorted from dorsal skin of 7 week-old C57BL/6 female mice by FACS. Samples were paired within individual mice (5 mice each). RNA from 500 cells were isolated and profile for transcriptome by sequencing.

overall_design: Dermal macrophage subtypes were sorted by surface antigens by flow cytometry followed by transcriptomic profiling with bulk RNA-seq.

first: Yuya

last: Ouchi

first: Eiichi

last: Takaki


title: Single-cell transcriptomic profiling of dermal leukocytes

summary: To decipher macrophage heterogeneity and kinetics during atopic dermatitis, dorsal skin of C57BL/6 female mice aged between 7-12 week-old received MC903 stimulation bi- or tri-daily. Dermal leukocyte-enriched single cells were prepared and analysed by single-cell RNA-seq in time course.

overall_design: Dermal cells enriched for leukocytes by anti-CD45 magnetic beads were profiled for single-cell transcriptomes by RNA-seq in time course.

first: Saki

last: Ishino


title: Bulk transcriptomic profiling of eosinophils from skin and bone marrow during atopic dermatitis

summary: Atopic dermatitis was induced on dorsal skin of 7-10 week-old C57BL/6 female mice by bi- or tri-daily MC903 treatment. On day 8, viable mouse eosinophils (CD45+F4/80+SiglecF+) were sorted from skin regions of healthy or vehicle/treated atopic dermatitis or femur/tibia-derived bone marrow by FACS. Samples were paired within individual mice (4 mice each). RNA from 500 cells were isolated and profile for transcriptome by sequencing.

overall_design: Dermal and bone marrow eosinophils were sorted by surface antigens by flow cytometry followed by transcriptomic profiling with bulk RNA-seq.


title: Transcriptomic Analysis of A549 cells (CC), corresponding 40 Gy radioresistant (RR) cells and respective tumorosphere cells (CCsp and RRsp)

city: Mumbai

first: Murali

middle: MS

last: Balla

state: Maharashtra

address: Trombay

department: Radiation Biology and Health Sciences Division

country: India

institute: Bhabha Atomic Research Centre

summary:
Initially radio-resistant cell line (40 Gy RR) was generated by treating A549 clonogenic cells with a dose of 5 Gy/fraction eight times.
We then evaluated Transcriptomic analysis of A549 cells (CC), generated radioresistant cells (RR) and respective tumorospheroids of A549 and radioresistant cells (CCsp and RRsp).

overall_design: Comparative gene expression profiling analysis of RNA-seq data for RR vs CC and RRsp vs CCsp was done

middle: S

first: Pooja

last: Melwani

first: Dhruv

last: Das

first: B

middle: N

last: Pandey


title: Gene expression profile at single cell level of glyoxylate induced calcium oxalate nephropathy mouse kidneys

city: shanghai

first: linxi

last: huang

address: 168 changhai road

institute: Changhai Hospital

summary: Kidney stones are prevalent. We used single cell RNA sequencing (scRNA-seq) to analyze the diversity of cells in mouse kidneys with nephrolithiasis.

overall_design: Kidney cells were collected from male mice receiving intraperitoneal injection of glyoxylate for successive 0, 1, 4 and 7 days and analyzed using scRNAseq.

first: Huang

last: Linxi

first: Chen

last: Wei

first: Guo

last: Zhiyong

first: Yu

last: Bing


title: ncRNAs associated with Lsd1

city: Taiepi

first: Ming-Chia

last: Lee

address: Library, Info & Research Bldg, Rm 904 #155, Sec. 2, Li-Nong St

department: Department of Life Sciences and Institute of Genome Sciences

institute: National Yang Ming Chiao Tung University

summary: This paired RIP experiment was done using Drosophila ovaries and designed to identified specific ncRNAs associated with Lsd1 (Lysine specific demethylase 1) complex in vivo.

overall_design: The RIP experiment was done using fly ovarian lysate and Lsd1-RIP was paired with a IgG-RIP experiment to normalize abundance of individual transcripts.

first: MIng-Chia


title: RORγ hijacks HIF-1α to promote peritoneal metastasis of gastric cancer.

city: GuangZhou

first: qianqian

last: wang

address: college of pharmacy in Sun Yat-Sen University

institute: Sun Yat-Sen University

summary: Peritoneal metastasis (PM) is diagnosed in almost half of patients with advanced gastric cancer (GCa) and has a very poor prognosis. However, the molecular mechanisms of PM in GCa remain poorly understood. Here, we show that the elevated expression of RAR-related orphan receptor gamma (RORγ) in GCa tumors is a key driver of PM. RORγ drives GCa progression and metastasis by assembling a transcriptional complex with HIF-1α that regulates the expression of HIF-1α targets via recruitment of RNA polymerase II and p300. Mechanistically, RORγ hijacks HIF-1α to disrupt the interaction between HIF-1α and PHD3, leading to decreased HIF-1α hydroxylation, ubiquitylation and increased HIF-1α accumulation, nuclear translocation, and transactivation. RORγ antagonists block tumor growth and PM in multiple xenograft GCa models, and they effectively sensitize GCa tumors to chemotherapy in mice. Thus, our study uncovers a mechanism of RORγ-driven PM and offers a potential therapeutic option against advanced GCa.

overall_design: A total of 4 samples were analyzed in this study.  Gastric cancer cell line AGS cells were transfected with siCont, siRORC, siHIF1A or siHIF1B for 24 h and cultured under hypoxia for additional 24 h. After treatment, all cells were collected for RNA-seq assay.

first: Junjian

last: Wang

first: Qianqian


title: mRNA, lncRNA and circular RNA expression profiles and ceRNA network construction of granulosa cells in ovarian endometriosis

city: Guangzhou

first: Jiayi

last: Guo

state: Guangdong

address: 员村二横路26号中山大学附属第六医院No.26, Erheng Road, Yuancun

department: Reproductive Medicine Research Center

institute: the Sixth Affiliated Hospital of Sun Yat-sen University

type: Non-coding RNA profiling by high throughput sequencing

summary: RNA sequencing was conducted for RNA expression profiling from GCs of five women with ovarian endometriosis and five with tubal factor infertility. The differential expression of mRNAs, lncRNAs, and circRNAs was compared. Then, the lncRNA-miRNA-mRNA and circRNA-miRNA-mRNA networks were constructed by co-expressing lncRNA/circRNA and mRNAs.

overall_design: mRNAs, lncRNAs and circRNAs expression profiles of five women with ovarian endometriosis and five with tubal factor infertility

first: Haitao

last: Zeng

first: Tingting

first: Xiaoyan

last: Liang

first: Jintao

last: Peng


title: Microarray gene expression profiling of mouse HSC treated with iron chelator deferoxamine (DFO)

city: Bronx

first: Britta

last: Will

state: NEW YORK

address: 1300 Morris Park Ave

department: Department of Cell Biology

institute: Albert Einstein College of Medicine

summary: We delineted the role for the intracellular labile iron pool in coordinating a cascade of molecular events which reinforce hematopoietic stem cell (HSC) identity by charaterizing and comparing the transciptome of HSC treated for 16hrs with an iron chlator (DFO, 10uM) vs. mock controls.

overall_design: For isolation of mouse HSC, bone marrow cells were isolated from tibiae, femurs, pelvic bones and vertebrae of wildtype C57/B6 mice at the age of 6 to 10-weeks. Low-density bone marrow mononuclear cells (BMMNC) were enriched by density gradient centrifugation using Histopague 1083 (Sigma-Aldrich, MO). BMMNC from 4 mice were then subjected to prospective isolation of HSC (Lin−Sca-1+c-Kit+CD150+CD48−) on a MoFlo Astrios platform (Beckman Coulter). Thereafter, FACS-sorted HSC from each biological replicate were exposed to the treatment of iron chelator (DFO, Sigma) or vehicle (water) for 16 hours.

first: Yun-Ruei

last: Kao


title: RORγ hijacks HIF-1α to promote peritoneal metastasis of gastric cancer

overall_design: A total of 7 samples were analyzed in this study. The study included three gastric cancer cell lines MKN45, AGS and HGC27. MKN45 cells were cultured in a normoxic incubator for 24 h or in a hypoxic incubator with certified gas containning 94% N2, 1%O2 and 5%CO2 for 24 h. AGS  cells were cultured in growth medium containing Vehicel control (DMSO) or GSK805 (5 μM) for 48 h. For HGC27,  cells transfected with Vector plasmid (HGC27-Vector) and RORγ overexpressing HGC27 stable transfectants (HGC27-RORC) were cultured in growth medium. After treadment, all cells were collected for RNA-seq assay.


title: Exercise ameliorates osteopenia in mice via intestinal microbial-mediated bile acid metabolism pathway

status: Public on Dec 24 2024

first: Congcong

last: Yu

address: Qingchundong road

institute: Zhejiang university

summary:
Rationale: Physical exercise is essential for skeletal integrity and bone health. The gut microbiome, as a pivotal modulator of overall physiologic states, is closely associated with skeletal homeostasis and bone metabolism. However, the potential role of intestinal microbiota in the exercise-mediated bone gain remains unclear.
Methods: We conducted microbiota depletion and fecal microbiota transplantation (FMT) in ovariectomy (OVX) mice and aged mice to investigate whether the transfer of gut ecological traits could confer the exercise-induced bone protective effects. The study analyzed the gut microbiota and metabolic profiles via 16S rRNA gene sequencing and LC-MS untargeted metabolomics to identify key microbial communities and metabolites responsible for bone protection. Transcriptome sequencing and RNA interference were employed to explore the molecular mechanisms.
Results: We found that gut microbiota depletion hindered the osteogenic benefits of exercise, and FMT from exercised osteoporotic mice effectively mitigated osteopenia. Comprehensive profiling of the microbiome and metabolome revealed that the exercise-matched FMT reshaped intestinal microecology and metabolic landscape. Notably, alterations in bile acid metabolism, specifically the enrichment of taurine and ursodeoxycholic acid, mediated the protective effects on bone mass. Mechanistically, FMT from exercised mice activated the apelin signaling pathway and restored the bone-fat balance in recipient MSCs.
Conclusion: Our study underscored the important role of the microbiota-metabolic axis in the exercise-mediated bone gain, heralding a potential breakthrough in the treatment of osteoporosis.

overall_design: RNA profiles of MSCs extracted from OVX mice receiving fecal microbiota transplantation from sedentary and exercised mice


title: Two opposite effects of desmoglein 3 on the growth of oral squamous cell carcinoma between anchorage -dependent and -independent conditions

city: Ichikawa-shi

first: junichirou

last: inada

state: Chiba

department: Department of Oral Oncology, Oral and Maxillofacial Surgery

institute: Tokyo Dental College

summary: Desmoglein 3 (Dsg3) is one of the desmosomal cadherins. Recent studies have reported that Dsg3 is abnormally expressed in oral squamous cell carcinoma (OSCC) and associated with tumor growth and poor survival. A role of Dsg3 in the progression of OSCC remains controversial, since both positive and negative effect on the cancer progression have been reported. Previously we have demonstrated that OSCC cells from the metastatic lymph nodes showed significantly higher DSG3 expression compared to those from the primary tumor of the same patients. Here we investigated the effect of Dsg3 expression on the growth of OSCC between anchorage-dependent (AD) and -independent (AID) conditions. Cell lines established from the primary tumor (P) and metastatic lymph nodes (LY) of three OSCC patients and two commercial OSCC cell lines were used for the experiments. Under AD conditions, Dsg3-low cell lines (Dsg3-low) had higher cell proliferation and migration ability than Dsg3-high cell lines (Dsg3-high) of the same patients. After transferred into AID conditions, all the cell lines except Dsg3-negative 7P showed increased Dsg3 expression by up to 50-fold, compared with AD conditions. Under AID conditions, all the patients showed higher cell proliferation ability in the Dsg3-high compared with Dsg3-low, which was marked contrast to AD conditions. Dsg3 knockdown under AD conditions increased the cell proliferation rate of all the cell lines except Dsg3-negative line. On the other hand, cell growth was not affected under AID conditions. These results suggested that Dsg3 may have two opposite effects on the growth of OSCC cells between AD and AID conditions, and that the involvement of molecules other than Dsg3 may also be important. Therefore, we investigated DEGs by Dsg3 knockdown under AD and AID conditions and their functions.

overall_design:
To investigate the differences in DSG3 function and DEGs on anchorage conditions, OSCC cell lines were cultured under AD and AID conditions, and DSG3 was knocked down by siRNA
DEGs were extracted when Dsg3-positive cells were knocked down.  Gene otology (GO) analysis was performed to identify the functional annotations of the extracted DEGs.

first: Michiyoshi

last: Kono

first: Masaki

last: Minabe


title: Transcriptomic signatures of antibody mediated rejection in early biopsies with negative histology in HLA incompatible kidney transplantation [RNA-seq]

city: Praha 4

first: Petra

last: Hruba

address: Videnska 1958

department: Transplant Laboratory

country: Czech Republic

institute: Institute for Clinical and Experimental Medicine

summary: Presensitized patients with circulating donor-specific antibodies (DSA) prior to transplantation are at risk for antibody-mediated rejection (ABMR). Peritransplant desensitization mitigates but does not eliminate the alloimmune response. We examined the possibility that subthreshold ABMR activity undetected by histology could be operating in some early biopsies.

overall_design: Whole-genome mRNA profiling was performed with RNA sequemcing  in 32 kidney transplant biopsies, retrospectively selected from all biopsies performed within the first month with availablesample in the Biobank.  Kidney allograft biopsy transcriptome in presensitized patients (DSA+) who had received desensitization and did not develop active or probable ABMR by histology (R-/DSA+, n=8) was compared with biopsies showing active/probable ABMR (R+/DSA+, n=16).  As negative controls, biopsies without rejection by histology performed within the identical time frame in patients without donor-specific antibodies at transplantation (R-/DSA-, n=8) were used .

first: Jiri

last: Klema

last: Mrazova

first: Eva

last: Girmanova

first: Katerina

last: Jaklova

first: Ludek

last: Voska

first: Martin

last: Kment

first: Martina

last: Mackova

first: Klara

last: Osickova

first: Vladimir

last: Hanzal

first: Philip F

last: Halloran

first: Ondrej

last: Viklicky


title: Nucleolar Stress-inducing Compounds Influence rDNA occupancy of RNA Polymerase I Transcription Machinery

city: Eugene

first: Victoria

last: DeRose

state: Oregon

address: 1370 Franklin Blvd.

department: Chemistry and Biochemistry

institute: University of Oregon

summary: Transcription of ribosomal RNA (rRNA) by RNA Polymerase I (Pol I) is often upregulated in cancer to facilitate rapid cell growth and proliferation, and has emerged as a potential target for chemotherapeutic agents. BMH-21 and Pt(II) chemotherapeutic agent oxaliplatin are well documented as inhibitors of Pol I activity, however the underlying mechanisms for this inhibition are not completely understood. Here, we applied chromatin immunoprecipitation sequencing (ChIP-seq) techniques and immunofluorescence imaging to probe the influence of oxaliplatin and BMH-21 on Pol I machinery. We demonstrate oxaliplatin and BMH-21 induce early nucleolar stress leading to the formation of “nucleolar caps” containing Pol I and upstream binding factor (UBF) which corresponds with broad reductions in ribosomal DNA (rDNA) occupancy of Pol I. Distinct occupancy patterns for the two compounds are revealed in ChIP-seq experiments. Taken together, our findings suggest that in vivo, oxaliplatin does not induce Pol I inhibition via interrupting a specific step in  Pol I transcription , while treatment with BMH-21 induced unique polymerase stalling at the promoter and terminator regions of the human ribosomal RNA gene.

overall_design: ChIP-seq of RPA194 and UBF in A549 and U2OS cells following treatment with cisplatin, oxaliplatin, or BMH-21.

first: Matthew

last: Yglesias


title: NAD+ metabolism restriction boosts high-dose melphanan efficacy in multiple myeloma patients

city: Munich

first: Gianluca

last: Santamaria

state: Germany

address: Ismaninger Strasse 22

department: Department of Medicine I

institute: Klinikum rechts der Isar – Technical University Munich

summary: A novel strategy to hinder the progression of multiple myeloma involves inhibiting NAD+ production. While solely targeting the NAMPT enzyme proved ineffective, the Preiss-Handler pathway, especially NAPRT1, emerged as pivotal in rescuing cancer cells. Cells lacking NAPRT1 become more susceptible to oxidative stress, and the dual targeting of NAMPT/NAPRT1 increased the efficacy of chemotherapy in multiple myelom.

overall_design: RNA samples extracted from tumoural CD138-positive plasmacells purified from 20 local NDMM patients  were profiled for correlation analysis with clinical data

first: Santamaria

last: Gianluca

first: Veneziano

last: Claudia

first: Soncini

last: Debora

first: Cea

last: Michele


title: Long non-coding RNA sequencing (RiboZero) analysis of monocytes-differentiated macrophages

city: Chicago

first: Afsar

middle: Raza

last: Naqvi

state: Illinois

address: 801 S Pauline

department: Periodontics

institute: University of Illinois

summary: Analysis of lncRNA differential expression in monocytes-derived macrophages M1 and M2 at 18h, Day 3, Day 5 and Day 7. StringTie was used to perform expression level for mRNAs and lncRNAs by calculating FPKM (FPKM=[total_exon_fragments/mapped_reads(millions)×exon_length(kB)]). The differentially expressed mRNAs and lncRNAs were selected with log2 (fold change) >1 or log2 (fold change) <-1 and with parametric F-test comparing nested linear models (p value < 0.05) by R package Ballgown.

overall_design: Total RNA was extracted using Trizol reagent (Invitrogen, CA, USA) following the manufacturer's procedure. The total RNA quality and quantity were analysis of Bioanalyzer 2100 and RNA 6000 Nano LabChip Kit (Agilent, CA, USA) with RIN number >7.0. Approximately 1 ug of total RNA was used to remove ribosomal RNA according to the manuscript of the Epicentre Ribo-Zero Gold Kit (Illumina, San Diego, USA). Following purification, the ribo-minus RNA fractions is fragmented into small pieces using divalent cations under elevated temperature. Then the cleaved RNA fragments were reverse-transcribed to create the final cDNA library in accordance with a strand-specific library preparation by dUTP method. The average insert size for the paired-end libraries was 300±50 bp. And then we performed the pair-end 2×150bp sequencing on an Illumina Hiseq 4000 platform housed in the LC Sciences (Hangzhou, China) following the vendor's recommended protocol.

first: Araceli

last: Valverde


title: The GTE4–EML chromatin reader complex concurrently recognizes histone acetylation and H3K4 trimethylation in Arabidopsis

city: Beijing

first: xinjian

last: He

address: No. 7, zhongguancun life science park road, changping district

institute: National Institute of Biological Sciences

summary: Histone acetylation and H3K4 trimethylation (H3K4me3) are associated with active transcription. However, how they cooperate to regulate transcription in plants remains largely unclear. Our study revealed that GLOBAL TRANSCRIPTION FACTOR GROUP E 4 (GTE4) binds to acetylated histones and forms a complex with the functionally redundant H3K4me3-binding EMSY-like proteins EML1 or EML2 (EML1/2) in Arabidopsis thaliana. The eml1 eml2 (eml1/2) double mutant exhibits a similar morphological phenotype to gte4, and most of the differentially expressed genes in gte4 were coregulated in eml1/2. Through chromatin immunoprecipitation followed by deep sequencing, we found that GTE4 and EML2 co-occupy protein-coding genes enriched with both histone acetylation and H3K4me3, exerting a synergistic effect on the association of the GTE4–EML complex with chromatin. The association of GTE4 with chromatin requires both its bromodomain and EML-interacting domain. This study identified a complex and uncovered how it cooperatively recognizes histone acetylation and H3K4me3 to facilitate gene transcription at the whole-genome level in Arabidopsis.

overall_design: Refer to individual Series


title: The profiles of mRNAs, lncRNAs and circRNAs in browning of human adipose derived stem cells

first: Zijun

last: Xu

address: 58 Zhongshan Road II

institute: The First Affiliated Hospital of Sun Yat-sen University

type:
Non-coding RNA profiling by array
Expression profiling by array

summary: To investigate the profiles of mRNAs, lncRNAs and circRNAs in browning of human adipose derived stem cells (hADSCs), we obtained hADSCs from omentum adipose tissues of 5 patients on who were performed abdominal operation and derived them into brown adipocytes. Then we employed microarray profiling the expression of lncRNAs, circRNAs and mRNA of hADSCs and their derived brown adipocytes.

overall_design: The profiles of lncRNAs, circRNAs and mRNAs in human omentum adipose derived stem cells of five patients and their derived brown adipocytes were examined by microarray profiling.

first: Xueying

last: Chen


title: GENE EXPRESSION ANALYSIS IN TOMATO (Lycopersicon esculentum) UNDER ENDOPLASMIC RETICULUM (ER) STRESS

city: Istanbul

first: Ozgur

last: Cakir

address: Vezneciler

country: Turkey

institute: Istanbul University

summary: To investigate the effect of ER stress on gene expressions in Tomato, RNA-seq was performed on 2 hours and 6 hours of tunicamycin applied samples.

overall_design: Comparative gene expression profiling analysis of RNA-seq data for 2 hours and 6 hours of ER stress-induced tomato plant leaves

first: Elif

last: Pulat

first: Özgür

last: Çakır


title: High efficient chromatin conformation capture with post-enrichment (HiChew) in single cells

status: Public on Dec 23 2024

city: Shenzhen

first: Chong

last: Tang

address: BGI Center, No.9 Yunhua Road, Yantian District

institute: BGI Genomics

summary: We present HiChew (High efficient chromatin conformation capture with post-enrichment), a novel method for analyzing three-dimensional chromatin organization in single cells and low-input samples. HiChew combines efficient sticky-end ligation with post-PCR enrichment using methylation-based selection, addressing key limitations of existing chromatin conformation capture methods. The method achieves significantly higher valid pair ratios (approximately 50%) compared to unenriched methods (8%) while maintaining high capture sensitivity. For single-cell applications, snHiChew demonstrates superior performance with 45-50% valid pair ratios and the ability to generate up to 7.3 million unique valid contacts per cell. This enhanced efficiency enables high-resolution mapping of chromatin interactions at 5-10 kb resolution with 70-80% bin coverage. We validate HiChew's accuracy through comparative analyses with conventional Hi-C data, showing high correlations in compartment scores, topologically associating domains (TADs), and loop detection. The method's scalability and cost-effectiveness make it particularly suitable for large-scale single-cell chromatin conformation studies. HiChew represents a significant advancement in chromatin architecture analysis, offering improved efficiency without compromising data quality or sensitivity.

overall_design: We conducted a comparative analysis of chromatin conformation capture methods for an unenriched Dip-C-like method, and HiChew on HEK293T cells and GM12878 cells.

first: Zhichao

first: Yeming

last: Xie

first: Chen

last: Tan

first: Fengying

last: Ruan

last: Zhang


title: Chromatin immunoprecipitation sequencing of transcription factor DUX4

city: Wuhan

first: Junjie

state: Hubei

address: Donghu Road, No. 115

department: Medical Research Institute

institute: Wuhan University

summary: ChIP-seq analysis of HEK293T-Tet-FLAG-DUX4 cells  infected with HSV-1

overall_design: HEK293T-Tet-FLAG-DUX4 cells were  infected with HSV-1 (MOI=2) for 14 h. Chromatin immunoprecipitation of DUX4 was performed with  anti-FLAG antibody (Proteintech, 20543-1-AP, 2ug) Two replicates are included for each samples.

first: Ming

last: Gao


title: Bisulfite sequencing of methylation changes in the D4Z4 region caused by HSV-1

type: Methylation profiling by high throughput sequencing

summary: Bisulfite-seq analysis of U2OS cells  infected with HSV-1

overall_design: U2OS cells were  infected with HSV-1 (MOI=5) for 12 h. The methylation status of the MID region of D4Z4 was analyzed by targeted bisulfite sequencing.


title: Cancer SLC3A2-mediated lysine uptake restricts T cell immunity against hepatocellular carcinoma

city: Xiamen

first: Yipeng

last: Rao

address: Xiangan Campus, Xiamen University, Xiangan Road, Xiangan District, Xiamen City, Fujian Province, China

institute: national insititute of diagnostics and vaccine development in infectious diseases（xiamen university）

summary: Our research demonstrates that in hepatocellular carcinoma (HCC), tumor cells outcompete T cells for lysine (Lys) by overexpressing the SLC3A2 transporter, thereby reducing Lys availability within the tumor microenvironment. This lysine deprivation results in decreased STAT3 levels in T cells, inhibiting their proliferation and effector functions, which ultimately accelerates tumor progression. Additionally, we identified a c-Myc-SLC3A2 regulatory axis activated by Lenvatinib, enhancing the sensitivity of HCC to the combined treatment with Lenvatinib and Lys.

sample_organism:
Homo sapiens
Mus musculus

platform_organism:
Homo sapiens
Mus musculus

overall_design: RNA sequencing (RNA-seq) was performed on CD3+ T cells cultured in fresh medium, Hepa1-6 supernatants, and Hepa1-6 supernatants supplemented with lysine. RNA-seq on control and SLC3A2 knockdown lentivirus-treated Huh-7 cells.

first: Chenghao

last: Huang

first: Yating

last: Chang


title: Identification of the H+-K+-ATPase ATP4A as hypoxia-regulated target for acute kidney injury prevention

city: HOUSTON

first: IN HYUK

last: BANG

state: TX

address: 6431 Fannin St

department: Anesthesiology

institute: UThealth at Houston

summary: Acute kidney injury (AKI) is the most common disease in critically ill patients and it is an important factor in the increase of morbidity and mortality yet the therapeutic strategy for AKI prevention is not established. Hypoxia Inducible Factors (HIFs) have been studied that play an important role during AKI to reduce its severity. Here we investigated to identify the novel therapeutic target of HIF2A during ischemic AKI. We performed microarray with the vechle- or PT2385 (HIF2A specific inhibitor) to find the downstream gene of Hif2a and identified that H+-K+-ATPase Atp4a was a leading candidate of HIF2A targeted gene which was suppressed by HIF2A  in the tubular epithelial cell. We further uncovered that pharmacological inhibition of Atp4a or genetic deletion of Atp4a reduced AKI during renal ischemia and reperfusion.

overall_design: Mice were performed with 30 minutes of ischemia and 24 hours of reperfusion for vehicle- or PT2385 treated (10 mg/kg of PT2384 was injecteed at 16 hours before surgery, 1 hour, 8 hours and 20 hours after surgery) mice .Rnal tubular epithelial cells were isolated from the kidney.

first: In

last: Bang

first: Yafen

last: Liang

first: Boyun

last: Kim

first: Adit

last: Ginde

first: Agieszka

middle: K

last: Czopik

first: German

last: Corrales

first: Bentley

last: Bobrow

first: Xinxin

last: Ma

first: Majd

last: Shaarani

first: Wei

first: Jieun

first: Katherine

last: Figarella

first: Yanyu

last: Wang

first: Charles

last: Green

first: Holger

last: Eltzschig


title: Developmental programming by maternal obesity alters offspring lifespan and immune function in a diet- and sex-specific manner

city: Bonn

first: Elvira

last: Mass

address: Carl-Troll-Str, 31

department: LIMES

institute: University of Bonn

summary: Maternal obesity is a growing health concern that predisposes offspring to metabolic dysfunction, immune system alterations, and neurodegenerative disorders. To investigate the intergenerational effects of maternal obesity, we used Drosophila melanogaster models exposed to high-sugar (HSD) and high-fat diets (HFD). We found that maternal diet-induced obesity significantly altered offspring lifespan, immune function, and neuronal health in a sex- and diet-specific manner. Male offspring were particularly susceptible, exhibiting reduced lifespan, impaired climbing ability, and increased axonal degeneration, especially following maternal HFD exposure. Transcriptomic analyses revealed age-dependent and diet-specific changes, with males showing pronounced alterations at 50 days of age. Developmental programming of hemocytes (macrophage-like cells) played a crucial role in these outcomes, as knockdown of key immune pathways such as Relish and Upd3 in hemocytes further influenced lifespan in a diet-specific manner. These findings highlight the complex interplay between maternal diet and immune function, underscoring the importance of immune cells in mediating the long-term health consequences of maternal obesity. Our study provides new insights into conserved mechanisms linking maternal metabolic health to offspring outcomes and emphasizes the continued need for animal models to understand intergenerational health impacts.

overall_design: Female flies were placed on one of three diets: CD (Control Diet), HSD (High Sugar Diet), or HFD (High Fat Diet) for 7 days, and mated with CD-fed male flies. The resulting offspring were maintained on CD, raised under light/dark cycles, and kept in a climate-controlled incubator at 25°C.

first: Seyhmus

last: Bayar

first: Lea

last: Seep

first: Nelli

last: Blank-Stein


title: Transcriptomic analysis of HepG2 cells overexpressing DNMT3A

first: Aixia

last: Zhai

address: 92 Fuhua Road, Futian District

department: The Eighth Affiliated Hospital

institute: Sun Yat-sen University

summary: Chronic hepatitis B virus (HBV) infection is the main etiology of liver fibrosis (LF), leading to cirrhosis and liver tumors.  DNA methylation caused by HBV protein changes the liver microenvironment and activates hepatic stellate cells, which is an important mechanism of liver fibrosis. However, the exact mechanism remains unclear. DNA methyltransferase 3A (DNMT3A) is a major enzyme that promotes DNA methylation. HBV infection promotes the expression of DNMT3A. To determine the specific roles of DNMT3A, we used lentivirus to overexpress DNMT3A in hepatocellular carcinoma cell line (HepG2). And the changes of transcriptome were analysed by RNA-seq.

overall_design: To explore the changes of transcriptome by DNMT3A, HepG2 cells were divided into two groups: cells infected with control lentivirus and cells infected with DNMT3A-overexpressing lentivirus. RNA-seq profiling the control and  DNMT3A overexpression HepG2 cells.

first: Yang

last: Liu

first: Xumeng

first: Yuetong

last: Li

first: Xin

last: Yu

first: Yanping

last: Zhang

first: Changlong

last: Bi


title: Multi-omic Sequencing of Intermediate to High-Risk Cutaneous Squamous Cell Carcinoma Identifies Critical Genes and Expression Patterns Associated with Disease and Poor Outcomes

city: Rochester

first: Tao

state: MN

address: 200 1st ST SW

institute: Mayo Clinic

summary: Cutaneous squamous cell carcinoma (cSCC) is one of the most common cancers in humans and kills as many people annually as melanoma. The understanding of the transcriptional changes with respect to high-risk clinical/histopathological features and outcome is poor. Here, we examine stage-matched, outcome-differentiated cSCC using whole exome and transcriptome sequencing. Exome analysis identified key driver mutations including TP53, CDKN2A, NOTCH1, SHC4, MIIP, CNOT1, C17orf66, LPHN2, and TTC16 and pathway enrichment of driver mutations in replicative senescence, cellular response to UV, cell-cell adhesion, and cell cycle. Transcriptomic analysis identified pathway enrichment of immune signaling/inflammation, cell-cycle pathways, extracellular matrix function, and chromatin function. Integrative analysis identified 183 critical genes in carcinogenesis and were used to develop a gene expression panel (GEP) for outcome. Three outcome-related gene clusters included those involved in keratinization, cell division, and metabolism. We found 16 genes that may predict metastasis (risk score ≥ 9 Met & risk score < 9 NoMet) with an AUC of 97.1%, sensitivity 95.5%, specificity 85.7%, and overall accuracy of 90%. Eleven genes were chosen to generate the risk score for Overall Survival (OS) with an OS prediction of 80.8% and each risk gene increasing the risk of death by 2.47 (HR: 2.47; p<0.001).

overall_design: Whole transcriptomic RNA-seq analysis and exome-seq anlysis were performed on primary tumor and control (normal skin) tissue, metastasis vs. non-metastasis.

first: Shams

last: Nassir

first: Miranda

last: Yousif

first: Xing

first: Kevin

last: Severson

first: Alysia

last: Hughes

first: Jake

last: Kechter

first: Angelina

last: Hwang

first: Blake

last: Boudreaux

first: Puneet

last: Bhullar

first: Richard

last: Butterfield

first: Zachary

last: Leibovit-Reiben

first: Alyssa

last: Stockard

first: Ewoma

last: Ogbaudu

first: Collin

middle: M

last: Costello

first: Steven

last: Nelson

first: David

last: DiCaudo

first: Aleksandar

last: Sekulic

first: Christian

last: Baum

first: Mark

middle: R

last: Pittelkow

first: Aaron

last: Mangold


title: Genome wide expression  profiling of S.pombe upon Atf1 over expression in Δpcr1 background

city: Kolkata

first: Geetanjali

last: Sundaram

state: West Bengal

address: 35, Ballygunge Circular Road

department: Biochemistry

institute: University of Calcutta

summary: The gene expression profile can be correlated with the morphogenetic change observed in cells where Atf1 has been over expressed in  Δpcr1 background

overall_design: Differential gene expression studies were carried out following over-expression experiments  in  S. pombe  transformants (Δpcr1+φ and Δpcr1+Atf1). Here we conducted an analysis to put forth the altered gene expression pattern in conditions where certain genes were over-expressed in presence or absence of another gene(s), as compared to physiological conditions.

first: Suchismita

last: Datta


title: Intestinal epithelial cell diversity and function in respect to age, anatomical localization, and microbial exposure - the proximal to distal transcriptome

city: Aachen

first: Mathias

last: Hornef

address: Pauwelstr. 30

department: Institute for Medical Microbiology

institute: University Hospital RWTH Aachen

summary: The small intestinal epithelium is composed of several defined epithelial cell lineages, which in turn exhibit marked transcriptional and functional diversity along the crypt-villus and proximal-to-distal length of the intestinal tract. While epithelial cell type and functional heterogeneity have been characterized in the adult intestinal epithelium, the temporal and spatial changes during the postanatal period, which accompany the transition from placental energy supply to enteral feeding and facilitate the establishment of the enteric microbiota and postnatal immune maturation, have not been systematically investigated. Here, we analyzed the proximal, medial and distal parts of the small intestinal epithelium of 1-, 5-, 10- and 25-day-old SPF mice by bulk RNA-Seq and used differential gene expression and pathway analysis to identify age-specific expression patterns. We identify gene clusters temporally expressed in the neonatal intestine and correlate their expression with the functional changes during postnatal tissue maturation and the neonate to adult transition.

overall_design: To study intestinal epithelial maturation during homeostatic conditions, intestinal epithelial cells (IECs) were isolated from the proximal, medial or distal part of small intestinal tissue obtained from 1-, 5-, 10- or 25-day-old C57Bl/6J specific pathogen-free (SPF) newborn mice. RNA was then isolated and RNA-Seq performed.

first: Johannes

last: Schöneich

first: Aline

last: Dupont


title: Intestinal epithelial cell diversity and function in respect to age, anatomical localization, and microbial exposure - the global transcriptome

summary: The small intestinal epithelium is composed of several defined epithelial cell lineages, which in turn exhibit marked transcriptional and functional diversity along the crypt-villus and proximal-to-distal length of the intestinal tract. While epithelial cell type and functional heterogeneity have been characterized in the adult intestinal epithelium, the temporal and spatial changes during the postnatal period, which accompany the transition from placental energy supply to enteral feeding and facilitate the establishment of the enteric microbiota and postnatal immune maturation, have not been systematically investigated. Here we analyzed the total small intestinal epithelium of 1-, 5-, 10-, and 25-day-old specific pathogen-free (SPF) and germ-free (GF) mice by bulk RNA-Seq and used differential gene expression and pathway analysis to identify age-specific expression patterns. In addition, the influence of enteric infection on the neonatal epithelium was investigated by bulk RNA-Seq. We identify gene clusters temporally  expressed in the neonatal intestine and correlate their expression with the functional changes during postnatal tissue maturation and the neonate to adult transition.

overall_design: To study intestinal epithelial maturation during homeostatic conditions and upon infection, intestinal epitehlial cells (IECs) were isolated from small intestinal tissue obtained from 1-, 5-, 10- or 25-day-old C57Bl/6J specific pathogen free (SPF) or C57Bl/6N germ free (GF) newborn mice. In addition, IECs were isolated from 5-day-old C57Bl/6J SPF newborn mice that had been orally infected 4 days earlier with 100-200 CFUs Salmonella Typhimurium. RNA was then isolated RNA and RNA-Seq performed.

first: Matthias

last: Schmitz

first: Isabel

last: Richter

first: Stefan

last: Schlößer


title: Anti-PD-1 exacerbates bleomycin-induced lung injury in mice via Caspase-3/GSDME-mediated pyroptosis

city: 广州

first: maolin

last: zhou

address: 广东省越秀区东风西路195号

institute: 广州医科大学

summary: To revealed the significant involvement of GSDME-mediated pyroptosis in the pathogenesis and development of ICI-LI

overall_design: Comparative gene expression profiling analysis of control group, BLM group and BLM+aPD-1.

first: Chengzhi

last: Zhou

first: Fei

last: Wang

first: Haiyi

last: Deng

first: Maolin


title: Intestinal epithelial cell diversity and function in respect to age, anatomical localization, and microbial exposure - the crypt/villus transcriptome

summary: The small intestinal epithelium is composed of several defined epithelial cell lineages, which in turn exhibit marked transcriptional and functional diversity along the crypt-villus and proximal-to-distal length of the intestinal tract. While epithelial cell type and functional heterogeneity have been characterized in the adult intestinal epithelium, the temporal and spatial changes during the postnatal period, which accompany the transition from placental energy supply to enteral feeding and facilitate the establishment of the enteric microbiota and postanatal immune maturation, have not been systematically investigated. Here, we analyzed microdissected crypt and villus structures of 1-, 5-, 10-, and 25-day-old SPF mice by 3'mRNA-Seq and used differential gene expression and pathway analysis to identify age-specific expression patterns. We identify gene clusters temporally expressed in the neonatal intestine and correlate their expression with the functional changes during postnatal tissue maturation and the neonate to adult transition.

overall_design: To study the difference between crypts and villi, 1 to 2 million µm² of crypts or villi were microdissected from small intestinal tissue obtained from 1-, 5-, 10- and 25-day-old C57Bl/6J specific pathogen-free (SPF) mice using laser-capture microdissection. RNA was then isolated and 3'mRNA-Seq performed.

first: Antoine-Emmanuel

last: Saliba


title: Intestinal epithelial cell diversity and function in respect to age, anatomical localization, and microbial exposure - the single cell transcriptome

summary: The small intestinal epithelium is composed of several defined epithelial cell lineages, which in turn exhibit marked transcriptional and functional diversity along the crypt-villus and proximal-to-distal length of the intestinal tract. While epithelial cell type and functional heterogeneity have been characterized in the adult intestinal epithelium, the temporal and spatial changes during the postanatal period, which accompany the transition from placental energy supply to enteral feeding and facilitate the establishment of the enteric microbiota and postnatal immune maturation, have not been systematically investigated. Here, we analyzed the small intestinal epithelium of 1-, 5-, 10- and 25-day-old SPF mice by single cell RNA-Seq and used differential gene expression and pathway analysis to identify age-specific expression patterns. In addition, the influence of enteric infection on the neonatal epithelium was investigated. We identify gene clusters temporally expressed in the neonatal intestine and correlate their expression with the functional changes during postnatal tissue maturation and the neonate to adult transition.

overall_design: To study intestinal epithelial maturation during homeostatic conditions, intestinal epithelial cells (IECs) were isolated from small intestinal tissues obtained from 1-, 5-, 10- or 25-day-old C57Bl/6J specific pathogen-free (SPF) newborn mice. In addition, IECs were isolated from 5-day-old C57Bl/6J SPF newborn mice that had been orally infected 4 days earlier with 100-200 CFUs Salmonella Typhimurium. scRNA-Seq was then performed.


title: Protective Role of 3-Mercaptopyruvate Sulfurtransferase (MPST) in the Development of Metabolic Syndrome and Vascular Inflammation

city: ATHENS

first: Paraskevas

last: Zampas

address: 4 Soranou Ephessiou St

country: Greece

institute: Biomedical Research Foundation of the Academy of Athens (BRFAA)

summary: Metabolic syndrome (MetS), a cluster of metabolic abnormalities that occur concurrently that significantly increases the risk of cardiovascular disease and mortality.  3-mercaptopyruvate sulfurtransferase (MPST), a cysteine-catabolizing enzyme that yields pyruvate and hydrogen sulfide (H2S), plays a central role in the regulation of energy homeostasis. Herein, we seek to investigate the role of MPST/H2S in MetS using a mouse model of the disease.Wilt type (WT) mice were fed a high-fat diet (HFD) for 15 weeks to induce obesity and hyperglycemia, and followed by a nitric oxide synthase inhibitor, for the additional 5 weeks to induce hypertension and MetS. This MetS mouse model caused a mild diastolic and endothelial dysfunction. We observed that, MetS was characterized by decreased levels of free H2S and sulfane-sulfur and downregulation of MPST in the aorta of animals with MetS. Global deletion of Mpst (Mpst-/-) results in increased body weight and greater glucose intolerance in mice with MetS, without affecting their blood pressure. Whole transcriptome analysis in aortic tissue revealed an upregulation of genes involved in the immune response; CD8+ cell infiltration and T-cell activation-related pathways were observed among the most affected biological processes in Mpst-/- mice with MetS.

overall_design: Having established that reduced vascular MPST expression is associated with HFD+LNAME mouse model of MetS, we investigated the impact of Mpst deletion in vascular gene expression in mice with MetS. For this purpose, we performed RNAseq analysis using aortas isolated from WT and Mpst-/- mice receiving HFD+LNAME and also aortas from WT mice fed with chow diet, considered as control group.

first: Andreas

last: Papapetropoulos


title: Transcript sequencing data in BT549 cell line.

city: Harbin

first: Wu

last: Hao

address: 哈尔滨市南岗区保健路6号

institute: Harbin Medical University

summary: To explore the DEGs in BT549 cell line treated with ENL.

overall_design: BT549 cell line treated with ENL


title: Wheat resistance response triggered upon recognition of the avirulence factor AvrStb6 hinders the penetration of Zymoseptoria tritici through stomata

city: Zurich

first: Cecile

last: Lorrain

state: Zurich

address: Universistätstrasse 2

department: Plant PAthology

country: Switzerland

institute: ETH Zurich

summary: Wheat (Chisenese Spring) and Zymoseptoria tritici AvrStb6-expressing virulent and avirulent strains transcriptomes analyses

sample_organism:
Triticum aestivum
Zymoseptoria tritici

platform_organism:
Triticum aestivum
Zymoseptoria tritici

overall_design: We performed a comparative transcriptomic approach to of wheat responses to i) a virulent strain 3D7-GFP, ii) an avirulent strain 3D7-GFP+AvrStb61E4, iii) mock inoculation with water that we used as negative control for infections assays and, iv) the infiltration of AvrStb6 purified protein, v)  infiltration of leaves with with PBS buffer used as a negative control for infiltration assay. All treatments were done in triplicates.

first: Julien

last: Alassimone

first: Coraline

last: Praz

first: Cécile

first: Andrea

last: Sanchez Vallet


title: Effects of LINC02154 knockdown on gene expression profiles in KON cells

city: Sapporo

first: Hiromu

last: Suzuki

state: Hokkaido

address: S1, W17, Chuo-ku

department: Department of Molecular Biology

institute: Sapporo Medical University

summary: We identified LINC02154 as a novel HNSCC-related lncRNA.  To study the function of LINC02154 in HNSCC cells, we knocked down LINC02154 in KON cells. We found that genes associated with cell cycle and mitochondrial genes were significantly affected by LINC02154 knockdown in KON cells.

overall_design: KON cells (1^10E5 cells) were transfected with  20 pmol Pre-designed DsiRNA (LINC02154 DsiRNA; Integrated DNA Technologies Inc.) or a  negative control DsiRNA (Integrated DNA Technologies Inc.) using a Lipofectamine RNAiMAX (Thermo Fisher Scientific) and were incubated for 72h.

first: Takeshi

last: Niinuma


title: Loss of CLN3 in HEK cells

city: Hershey

first: Nuno

last: Raimundo

state: PA

address: 500 University Dr, College Of Medicine, Room C4769

department: Cellular and Molecular Physiology

institute: Penn State College of Medicine

summary: To understand the consequences of CLN3 loss, we performed RNAseq in HEK cells with CRISPR-Cas9-mediated KO of CLN3 (CLN3-KO) or parental HEK WT cells.

overall_design: three parental HEK WT, three CLN3-KO


title: PRR14 mediates mechanotransduction and regulates myofiber identity via MEF2C in skeletal muscle

city: Changsha

first: Mei

last: Yang

address: 139 Middle Renmin Road

institute: The Second Xiangya Hospital, Central South University

summary: the expression of TF MEF2C is decreased in skeletal muscle of PRR14-KO mice,which displays sarcopenia phenotype. Meanwhile, increasing MEF2C's expression in skeletal muscle lessens the phenotype.

overall_design: To investigate MEF2C's function in the regulation of skeletal muscle's mass and function, we increased MEF2C's expression through AAV virus in the skeletal muscle of PRR14-KO mice. We then performed gene expression profiling analysis using data obtained from RNA-seq of PRR14-KO skeletal muscle injected with AAV virus for 1 month.


title: MYO7a is required for the functional integrity of the mechanoelectrical transduction complex in the outer hair cells of the adult cochlea.

city: Paris

first: Fiorella

last: Grandi

address: 105 Bld d'Hopital

department: Centre de Recherche de Myologie

country: France

institute: Sorbonne Universite

summary: Myosin-VIIA (MYO7A) in an unconventional myosin responsible for syndromic (Usher 1B) or non-syndromic recessive deafness in humans when mutated. In the cochlea, MYO7A is expressed in the stereocilia of both inner and outer hair cells, where it is believed to act as the motor protein tensioning the mechanoelectrical transducer (MET) channel. Whether this tensioning role is a common feature among both types of cochlear hair cells is unknown. Here we show that MYO7A has a distinct role in adult outer hair cells (OHCs), being crucial for the structural integrity of the MET complex. Postnatal deletion of MYO7A did not affect the staircase structure of the hair bundles but caused a progressive reduction of the size of the MET current without affecting the resting open probability and calcium sensitivity of the MET channel. The hair bundle of OHCs deficient in MYO7A also showed reduced bundle stiffness and was highly susceptible to noise exposure. RNA-sequencing identified the down-regulation of several stereociliary proteins in the Myo7a-deficient cochlea. This study reveals that IHCs and OHCs use different mechanisms to maintain the MET channel in its most sensitive resting open position, and confirms that in OHCs,  this mechanism is MYO7A independent.

overall_design: For the conditional knockout mice (Myo7afl/flMyo15-cre+/-), the targeted tm1a allele for Myo7a (Myo7atm1a(EUCOMM)Wtsi allele ID: 4431921) was generated by the Mouse Genetics Programme at the Wellcome Trust Sanger Institute (Cambridge, UK). For Myo7a the critical exons 10 and 11 were floxed and the tm1c allele was obtained by crossing the tm1a mouse to a FLPeR carrying mouse (Rosa26Fki). The tm1d alleles, which were used for the experiments, were obtained by crossing the tm1c mouse (Myo7afl/fl) with the Myo15-cre mice. For experiments littermate control Myo7afl/flMyo15-cre+/+ (referred in the manuscript as Myo7afl/fl) and knockout mice (Myo7afl/flMyo15-cre+/-) were used.

first: Anna

last: Underhill

first: Walter

last: Marcotti


title: MEF2C chip in the skeletal muscle of PRR14-KO mice

summary: the expression and splice forms are regulated in the skeletal muscle of PRR14-KO mice, to  explore the underlying mechanism of MEF2C-mediated PRR14's function in skeletal muscle, the chip assay was performed

overall_design: MEF2C chip assay was performed in the skeletal muscle of PRR14-KO mice and  PRR14-WT mice.


summary: Sarcopenia, characterized by the loss of muscle mass, strength, and function, predisposes adverse outcomes and its mechanism is waiting to reveal. Here, we report decrease of PRR14, a nuclear protein, in skeletal muscle results in sarcopenia. Genetically, genome-wide association studies (GWAS) identified multiple single nucleotide polymorphisms (SNPs) in PRR14 locus associated with body mass index (BMI) and total body lean mass, which indicated its association with sarcopenia; Specific knockout of skeletal muscle Prr14 in mice confirmed the causal effect; Biochemical analysis and high-throughput sequencing, including both transcriptome and approaches for the study of the epigenome (CUT&Tag sequencing and ATAC sequencing), revealed that Prr14 was required for myofiber homeostasis in skeletal muscle: Prr14 loss altered chromatin structure and reduced Mef2c activity, which in combination resulted in failure of maintaining myofiber identity and therefore sarcopenia. Our findings demonstrate that PRR14 orchestrates critical epigenetic changes and transcription factor activity to maintain myofiber identity, thereby providing novel therapeutic avenues for skeletal muscle pathologies associated with dysregulation of these mechanisms.

overall_design: total RNA of the quadriceps femoris from both Prr14-KO and Prr14-WT mice was purified and ONT sequenced


overall_design: ATAC-seq of samples from the quadriceps femoris from both Prr14-KO and Prr14-WT mice


summary: This SuperSeries is composed of the SubSeries listed below.

overall_design: Refer to individual Series


title: Metabolic analysis of amelablastoma at single-cell level

first: qiwen

last: man

address: Luyu road

institute: wuhan university

summary: Here, we performed single cell RNA sequencing (scRNA-seq) analysis from ameloblastoma patients  (n=3). The metabolic landscape of different cell types was analyzed based on metabolic pathway gene sets. Surprisingly, hypoxia correlates with both oxidative phosphorylation and glycolysis activity at single-cell level in tumor cells of amelablastoma.

overall_design: Single cell RNA sequencing (scRNA-seq) analysis of  ameloblastoma (n=3) was performed and the metabolic genes were explored in tumor cells and stromal cells.

first: Qi-Wen

last: Man

first: Rui-Fang

last: Li


title: The evaluation of exosomal miRNA biomarkers for cachexia

city: Xi'an

first: Xunliang

last: Jiang

address: No. 169, Changle West Road, Xincheng District, Xi'an, Shaanxi

institute: Air Force Military Medical University

summary:
In order to screen miRNAs related to cachexia, we collected plasma from patients with gastric cancer cachexia or without cachexia, and extracted exosomes from plasma.
Then, we analyzed the gene expression profile of 3 gastric cancer patients with cachexia and 2 gastric cancer patients with non cachexia.

overall_design: Comparative gene expression profile analysis of RNA seq data between patients with gastric cancer cachexia and patients with gastric cancer without cachexia.

first: Rui

last: Zhang


title: Immune profiling of premalignant lesions in patients with Peutz-Jeghers Syndrome

summary: RNA sequencing was performed in a total of 26 colorectal tissues from 26 unrelated patients including PJS polyps (n=6), familial adenomatous polyposis (FAP) polyps (n=9), paracancerous colonic mucosae (ConA) (n=9) as well as non-PJS and non-FAP sporadic polyps (ConB) (n=5)

overall_design: mRNA profiles of colorectal tissues from PJS polyps, FAP polyps, paracancerous colonic mucosae and non-PJS and non-FAP sporadic polyps


title: Transcriptome wide high throughput mapping of protein-RNA interactions across human cell lines using POP-seq

city: Pittsburgh

first: Rajneesh

last: Srivastava

state: Pennsylvania

address: 450 Technology Dr

department: Surgery, University of Pittsburgh

institute: McGowan Institute for Regenerative Medicine

summary: Protein-RNA interactions are critical for post-transcriptional regulatory processes that govern RNA metabolism. Several existing high throughput methods based to detect these interactions are reported for the biases associated to the inherent crosslinking approaches. In this study, we used Protein Occupancy Profile-Sequencing (POP-seq), a phase separation based method that does not require crosslinking, to examine the regulatory protein RNA interactions in cancer cell lines: K562, HepG2, A549, MCF7, Jurkat, and HEK293. POP-seq provides unbiased protein occupancy profiles in a transcriptome wide manner due to its crosslinking free approach. Our study demonstrates that POP-seq can enrich the protein occupied sites with over 60,000 peaks identified across multiple cancer cell lines. In our initial analysis, we compared POP-seq identified interactions with two protocols in presence and absence of UV crosslinking in K562 and HepG2 cells and results showed >70% overlap between the two approaches at the gene level, indicating that POP-seq can efficiently map the unbiased protein occupied sites in transcriptome wide manner. Using downstream bioinformatics analysis we found majority of POP-seq peaks on the exonic region of the transcript followed by introns and 3’ UTRs, while less than 10% abundance was recorded for repetitive elements like SINEs and LINEs. Among the various gene types, we found abundance of POP-seq peaks on protein coding genes followed by non-coding RNAs, that are typically highly expressed in cancer cell lines. We used CRISPR Cas 9 system to evaluate the functionality of POP-seq sites and observed that identified interactions could potentially impact the expression of nearby exons.  Overall, this study provides the first comprehensive resource of transcriptome wide protein-RNA interaction maps in multiple cell line using a crosslinking free approach that further opens the opportunity to implement the method in primary tissues for detecting the regulatory interactions.

overall_design:
To investigate the transcriptome wide protein occupied sites across multiple cell lines, we implemented Protein Occupancy Profile-Sequencing (POP-seq) that generate precise RNA fragments targeted by RBPs.
Lead contact: scjanga@iu.edu

first: Mansi

first: Sarath Chandra

last: Janga


title: Effects of CYTOR Knockdown via CRISPRi on K562 cells

status: Public on Dec 22 2024

city: New York

first: Avi

last: Ma'ayan

state: NY

address: One Gustave L. Levy Place, Box 1603

department: Pharmacological Sciences

institute: Icahn School of Medicine at Mount Sinai

summary: The long noncoding RNA CYTOR has been linked to poor prognosis of cancer, this includes chemo- and radioresistance. Knowing the mechanisms of CYTOR can benefit current cancer therapeuitics. To examine the mechanisms of CYTOR on K562, we performed CRISPRi to knock it down. RNA sequencing were then performed on these knocked down and wild type cells. This is followed by differential gene expression analysis to determine genes and lncRNAs that are differentially regulated when CYTOR is silenced.

overall_design: To illustrate how CYTOR affect the transcription of genes and lncRNAs on K562 cells, we profiled 4 replicates of CYTOR knocked down, and wild type K562 cells

first: Assaf

last: Bester


title: Chronic sleep deprivation promotes experimental autoimmune uveitis through STAT1 phosphorylation, ISG15 expression and enhanced pathogenicity of macrophages

city: Wu Han

first: Zhen

last: Chen

state: Hu bei

address: Zhangzhidong Road

institute: Renmin Hospital of Wuhan University

summary: Autoimmune uveitis (AU) is a severe intraocular inflammatory disease driven by dysregulated T-cell immunity and macrophage activation, leading to retinal tissue damage. Experimental autoimmune uveitis (EAU), an animal model, closely mimics human AU, highlighting the role of macrophages in inflammation and immune regulation. Chronic sleep deprivation (CSD), caused by prolonged circadian rhythm disruption, further exacerbates immune dysfunction by activating microglia and enhancing inflammation. This study investigates the combined impact of EAU and CSD on retinal transcriptomics, focusing on immune and inflammatory pathways, providing insights into the interaction between circadian rhythm disruptions and autoimmune uveitis progression.

overall_design: Heathy B10.RIII mices rep1, rep2, rep3;Chronic sleep deprivation treatment of healthy B10.RIII mice for 4 weeks;Treatment of  B10.RIII mice using  IRBP peptide emulsified 1:1 with complete Freund's adjuvant (CFA) containing inactivated Mycobacterium tuberculosis for 2 weeks  rep1, rep2, rep3;Treatment of B10.RIII mices using IRBP peptide emulsified 1:1 with CFA containing inactivated Mycobacterium tuberculosis for an additional 2 weeks, followed with chronic sleep deprivation for  4 week rep1, rep2, rep3:


title: Enterococcus faecium activates BMP/SMAD-mediated osteoblastogenesis and Wnt mediated neurogenesis while inhibiting PD

city: Seoul

first: Jeung Hee

last: An

address: 47 Kkachisan-ro 24-gil, Gangseo-gu

institute: Gangseo University

summary: Parkinson's disease (PD) is defined by neurodegeneration, muscle atrophy, and bone deterioration, largely due to dopamine depletion. This study evaluates the therapeutic potential of heat-killed Enterococcus faecium FBL1 (HEF) in mitigating PD-related dysfunction through osteoblastogenesis and neurogenesis pathways. In the rotarod test, MPTP-treated mice exhibited a significant reduction in walking time, 4.1 times lower than that of the normal group. However, treatment with HDF notably improved the retention time, with a dose-dependent increase, compared to MPTP group. Wire-hanging test showed enhanced muscle strength, as HEF-treated mice demonstrated a 2.1- and 3.3-fold increase in the latency to fall at low and high doses, respectively, when compared to MPTP group. Grip strength and forced swim test, further supported the findings of neuromuscular recovery and reduced immobility in the HEF treated mice. The alpha-synuclein aggregation in the brain and muscle induced by MPTP were attenuated by HEF. Volcano plot analysis of muscle tissue revealed that MPTP treatment caused significant dysregulation, with 142 upregulated and 163 downregulated genes, including the downregulation of Wnt signaling-related genes Astn1 and Frat2, which are involved in neurogenesis and muscle regeneration. Conversely, the osteogenesis-related gene Pbx1 was upregulated by HEF, compared to MPTP treated group. Treatment with HEF also restored gene expression, notably increasing Tnxb, essential for tissue integrity, and Gsn, involved in various biological processes, compared with MPTP. Key markers of skeletal muscle differentiation (Myf5, MyoG, Myh1), osteoblastogenesis (Bmp2, Bmp4, SMAD1/5/8, RUNX2), and neurogenesis (Wnt3a, Beta-catenin, TCF1, LEF1) were downregulated in MPTP-induced PD but restored by HEF. Inflammatory markers (TNF-alpha, iNOS, and NF-kappaB) were significantly elevated in the MPTP group. However, these levels were reduced by HEF in a dose-dependently. This study highlights the pivotal role of osteoblastogenic (BMP/SMAD signaling) and neurogenic (Wnt signaling) pathways in maintaining muscle and bone homeostasis in PD. HEF offers a novel therapeutic approach targeting the BMP/SMAD and Wnt signaling pathways to mitigate muscle and bone degeneration in patients with PD.

overall_design: A PD model was established in C57BL/6 mice using MPTP, followed by treatment with heat-killed En. faecium FBL1 at various doses. Behavioral assessments (rotarod, grip strength, wire hanging, and forced swimming tests) evaluated motor function, while RNA sequencing of the brain and muscle tissues analyzed differentially expressed genes. Enrichment analysis focused on pathways related to neurogenesis, osteoblastogenesis, and neuroinflammation.

first: Da Hye

last: Song

first: Yu Rim

last: Lee

first: Seung Min

last: Yu

first: Soo Youn

first: Yu-Jin

last: Choi

first: Sae Hun

last: Kim