title: Single-Cell RNA Sequencing of Baseline PBMCs Predicts ICI efficacy and irAE Severity in NSCLC Patients

city: Buk-gu

first: GyeongDae

last: Kim

state: Gwangju,

address: 123, Cheomdangwagi-ro

department: Life Science

institute: gwangju institute of science and technology

summary: Immune checkpoint inhibitors (ICIs) have revolutionized by offering remarkable clinical benefits and durable responses for patients with advanced non-small cell lung cancer (NSCLC). However, a very small percentage of patients responded to ICI treatment, and immune-related adverse events (irAEs) leading to treatment discontinuation remain challenges. Despite the recognized need for biomarkers that can predict both the efficacy of ICIs and the risk of irAEs, such biomarkers have yet to be clearly identified. In this study, we performed single-cell RNA sequencing on peripheral blood mononuclear cells (PBMC) from NSCLC patients prior to treatment with ICIs. We found that the immune response is generally reduced in patients with poor prognosis. However, the hypoxic environment is particularly more prominent in patients with primary resistance compared to those with acquired resistance. Meanwhile, granzyme and perforin are closely associated with favorable prognosis. We also identified IL1B and CXCL8 as key predictors of irAEs, with their activation linked to inflammation. Moreover, we found that PRF1 in CD8+ T cells and NK cells plays a critical mediator of complete responses and reduced irAE to ICI therapy. These findings deepen our understanding of the mechanisms of ICI efficacy and provide valuable information for optimizing immunotherapy strategies. By identifying biomarkers for both better prognosis and irAEs, this research lays the foundation for personalized immunotherapy approaches that aim to improve clinical outcomes while minimizing the risks associated with ICI treatment.

overall_design:
Peripheral blood samples were obtained from patients prior to ICI administration. Peripheral blood mononuclear cells (PBMCs) for single cell RNA sequencing analysis were separated from whole blood utilizing standard Ficoll-Paque (GE Healthcare, Uppsala, Sweden) density gradient centrifugation, frozen in freezing media, and stored in liquid nitrogen until use. The single-cell library was prepared using the 10X method and sequenced by HiSeq2500.

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Raw files for human/patient samples were not submitted to GEO due to concerns about submitting personally identifiable sequence data for open access.
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first: Gyeong Dae

first: Da Hyun

last: Kang

first: Jihwan


title: Multi-omics Profiling of the Lateral Ventricle Choroid Plexus Reveals Temporal Cellular Remodeling, Early Immune Gene Activation, and a Novel Epithelial Subtype [scRNA-seq]

status: Public on May 19 2025

city: Stockholm

first: Mónica

middle: da Silva

last: Fernandes

address: Nobels väg 6

country: Sweden

institute: Karolinska Institutet

type: Expression profiling by high throughput sequencing

summary: Healthy brain development and function highly depend on the choroid plexus. Temporal alterations in the cellular landscape and gene expression of choroid plexus cells, whether in health or disease, can alter immune cell trafficking in the brain and cerebrospinal fluid composition, ultimately impacting brain dynamics. Here, we performed a comprehensive multi-omics analysis—including bulk and single-cell transcriptomics and epigenomics—of the lateral ventricle choroid plexus across early postnatal and adult stages in mice and rats. We uncovered striking fluctuations in the choroid plexus cellular composition from neonatal to adult stages, accompanied by transcriptional remodeling of all main cell types. Immune profiling revealed a marked increase in immune cells in adulthood and an altered cell-type diversity through time. Surprisingly, we observed an early activation of host-defense genes in choroid plexus cell, beginning in the neonatal period and progressively increasing into young adulthood.  Epithelial cells exhibited subtype diversity and plasticity, with distinct gene expression programs and chromatin accessibility profiles emerging over time. Notably, we identified a previously unrecognized epithelial cell subtype with unique gene markers suggesting a specialized function. Ligand-receptor interaction analysis revealed a progressive remodeling of cellular crosstalk networks during CP maturation, suggesting dynamic intercellular signaling as the tissue develops. Our study offers a comprehensive atlas of gene activity and chromatin accessibility in the lateral ventricle CP cells, providing a valuable resource to guide future efforts in targeting gene expression at the CP for therapeutical purposes.

overall_design: We have collected the choroid plexus from the lateral ventricles of C57BL/6 mice at the following developmental time points: postnatal day (P)2/3, P11 and P60.  We then performed scRNA-seq analysis.

first: Lili

last: Li

first: Eduarda

last: Correia

first: Alice

last: Vieira

first: Diana

last: Afonso

first: Jonas

last: Campos

first: Neemat

last: Mahmud

first: Mandy

last: Meijer

first: Eneritz

last: Agirre

first: Nobrega

last: Claudia

first: Fernanda

last: Marques

first: Gonçalo

last: Castelo-Branco

first: João Carlos

last: Sousa

first: Ana Mendanha

last: Falcão


title: U1 snRNP regulates alternative promoter activity by inhibiting premature polyadenylation [TT-seq]

city: Boston

first: Ana

last: Fiszbein

state: MA

address: 24 Cummington Mall, LSE(Life Science and Engineering) Building

department: Biology

country: USA

institute: Boston University

summary: Transcription and splicing are intricately linked processes, with emerging evidence highlighting the involvement of splicing factors mediating their coupling. U1 small nuclear ribonucleoprotein particle (U1 snRNP), a key splicing factor, not only serves as the initial component of the spliceosome but also plays a crucial role in preventing premature cleavage and polyadenylation, facilitating long-distance transcription elongation. Here, we show that U1 snRNP regulates alternative promoter usage through inhibition of premature polyadenylation. Inhibiting U1 snRNP with antisense oligonucleotides or introducing a premature polyadenylation leads to a significant decrease in downstream promoter activity in genes with premature polyadenylation sites in between two promoters. Conversely, restoring U1 snRNP activity or inhibiting premature polyadenylation sites using a gene-specific U1 snRNP rescues downstream promoter activity. Mechanistically, U1 snRNP inhibition correlates with reduced chromatin accessibility and serine 5 phosphorylation levels of RNA polymerase II at downstream promoters. Our findings propose a model where U1 snRNP facilitates productive transcription from upstream promoters, triggering downstream promoter activation by destabilizing nucleosomes and promoting promoter escape.

overall_design: Six samples with two distinct experimental conditions were investigated by transient transcriptome sequencing (TT-seq): 3 biological replicate sets of cells treated with a Control antisense morpholino oligonucleotides (Control AMO) and 3 biological replicate sets of cells treated with a U1 antisense morpholino oligonucleotides (U1 AMO).


title: Indentifying the binding site of FL1 on DNA in blue light condition

city: Shanghai

first: Desheng

last: Zeng

address: 300 Feng Lin Road

country: China

institute: CAS Center for Excellence in Molecular Plant Science

type: Genome binding/occupancy profiling by high throughput sequencing

summary: FLs can regulate the transcription of a series of downstream genes. Therefore, this sequencing was devised to verify whether FL1 can associate with the chromatin of these downstream genes.

overall_design: For the verification of FLs' chromatin associating ability, 10-day-old seedlings of WT, FL3-Flag grown under continuous blue light (30 μmol·m−2·s−1) were used. Anti-Flag affinity beads were used for immunoprecipitation.

first: Hongtao

last: Liu


title: Gene expression profile at single cell level of lung tissue in VeNx and SuHx rats

city: Shenzhen

first: Fan

last: Qiu

address: 3025 Shennan Middle Road

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

summary: We performed single-cell RNA sequencing of lung tissue obtained from sugen-5416 and hypoxia (SuHx) rats and the control rats exposed to vehicle and normoxia (VeNx) to identify the heterogeneity of cells of interest.

overall_design: 3 SuHx (3 weeks of SuHx and 3 weeks of normoxia) and 2 VeNx lung samples were obtained.


title: EZH2 loss promotes gastric squamous cell carcinoma

city: Chengdu, China

first: Ailing

last: Zhong

state: Sichuan

address: No.17 Renmin road section3

department: State Key Laboratory of Biotherapy, West China Hospital, Sichuan University.

institute: Sichuan University

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

overall_design: Refer to individual Series


title: Esoinophilic fasciitis and morphea share gene signatures of inflammatory cell death, self-DNA recognition, and JAK/STAT signaling

first: William

last: Crisler

state: Massachusetts

address: 221 Longwood Ave

department: Dermatology

institute: Brigham & Women's Hospital

summary: The pathogenesis of eosinophilic fasciitis (EF) and morphea is poorly understood. We analyzed skin biopsies from EF and morphea patients compared to adult healthy skin (HS) using gene expression profiling, Ingenuity Pathway Analysis, and immunostaining. EF gene expression showed significant overlap with morphea. 51/61 differentially expressed genes (DEG), 80/99 canonical pathways, and 40/51 upstream regulators were shared in EF and morphea. Both conditions exhibited robust T cell activation and cytotoxic signatures despite their pauci-inflammatory histological appearance, suggesting small numbers of T cells may drive injury, inflammation, and fibrosis. EF and morphea shared signatures of necroptosis, self-DNA recognition, cGAS/STING activation, induction of types I, II, and III interferon signaling, and fibrosis. Seven JAK/STAT molecules were significantly upregulated in EF and nine were upregulated in morphea. Compared to HS, TYK2 was the most significant JAK molecule upregulated in EF (p=0.0007) and morphea (p=0.0002). Immunostaining demonstrated activated interferon-related molecules JAK1 and STAT1 in T cells, dendritic cells, and macrophages in both diseases. This study identifies shared molecular mechanisms of EF and morphea and demonstrates strong pathophysiologic similarities between the two diseases. Our findings indicate that targeted inhibition of JAK/STAT molecules and mediators of necroptosis may be beneficial in treating these fibrotic diseases.

overall_design: This study uses Nanostring transcriptional profiling with the Human Autoimmune Panel (NS_Hs_AI_Pro_v1.1). Samples incluce lesional biopsies from patients with morphea (n=8), eosinophilic fasciitis (n=6), and healthy adults (n=8). We used nSolver 4.0 for analysis to compare morphea samples vs. normal skin, and separately compared eosinophilic fasciitis samples vs. normal skin.

middle: J

first: Avery

middle: H

last: LaChace

first: Rachael

middle: A

last: Clark


title: Visceral adipocyte metabolic dysfunction in obesity related to altered chromatin accessibility to thyroid hormone receptor [RNA-seq]

city: nanjing

first: Hao

last: Zhu

address: 300 guangzhou road

institute: nanjing medical university

summary: Adipocyte dysfunctuon exacerbates obesity, yet the onset of adipocyte dysfunction is still unclear. Here, we employed RNA-seq and ATAC-seq on visceral adipose tissue from individuals with obesity or normal weight.Our research identified differentially expressed genes (DEGs) of VAT from individuals with normal wight or obesity enriched in pathways related to adipocyte metabolic function, thyroid hormone receptor binding sites were discovered in the accessible chromatin regions of these DEGs, including STAT5B. Motif enrichment, CHIP assay and in vitro cell experiments confirmed the decreased activation of STAT5B by triiodothyronine (T3) through binding with thyroid hormone receptor alpha (THRa) in obesity. In addition, RNA interference revealed STAT5B as a key transcription factor in maintaining the metabolic function of VAT. In conclusion, the impaired metabolic function of VAT is associated with altered chromatin accessibility to thyroid hormone (TH) in obesity. STAT5B is a key transcription factor at the core of the disrupted thyroid-adipose signaling and might be a promising target to improve obesity.

overall_design: RNA-seq and ATAC-seq on visceral adipose tissue from 3 human individuals with normal weight and 3 human inviduals with obesity.

first: Wen-Na

last: Zhang

first: Xiao-dong

last: Wang


title: U1 snRNP regulates alternative promoter activity by inhibiting premature polyadenylation


title: Differential effects of tofacitinib on macrophage activation contribute to lack of response in ulcerative colitis patients

city: Barcelona

first: Azucena

last: Salas

address: Rosselló, 149-153

department: Gastroenterology

country: Spain

institute: IDIBAPS

summary: The variability and unpredictability of drug efficacy in ulcerative colitis (UC) patients, including tofacitinib, an oral JAK1 and JAK3 inhibitor, remains a perplexing reality. Here, we use single-cell RNA sequencing (scRNA-seq) analysis of intestinal cells from UC patients receiving tofacitinib to identify the cellular subsets and genes involved in the response and/or resistance to tofacitinib.

overall_design: Colon biopsies from patients with active UC starting tofacitinib were collected at baseline (n=11) and during follow-up (n=12) and processed by scRNA-seq.

first: Elisa

last: Melón-Ardanaz


title: U1 snRNP regulates alternative promoter activity by inhibiting premature polyadenylation [CUT&RUN]

summary: Transcription and splicing are inherently intertwined. Accumulating evidence support a role of splicing factors in mediating this coupling. U1 small nuclear ribonucleoprotein particle (U1 snRNP), a key splicing factor, acts as the initial building block of the spliceosome, interacting with nascent pre-mRNA at 5' splice sites. In addition to its role in splicing, U1 snRNP is crucial for preventing premature cleavage and polyadenylation, enabling long-distance transcription elongation. Here, we show that U1snRNP can regulate the usage of alternative promoters through its role in inhibiting premature polyadenylation. Using antisense oligonucleotides to inhibit U1 snRNP, we first observed a markedly decrease in downstream promoter activity at the newly synthesized RNA level. Interestingly, U1 snRNP inhibition selectively impacts downstream promoters of genes featuring premature polyadenylation sites located between two promoters. Overexpressing a wild-type U1 snRNP or a gene-specific U1 snRNP designed to inhibit premature polyadenylation sites restores downstream promoter activity. Conversely, introducing a premature polyadenylation site between two promoters reduces downstream promoter activity. Exploring the underlying molecular mechanisms, we identified a substantial decrease in serine 5 phosphorylation levels in newly recruited RNA polymerase II at downstream promoters following U1 snRNP inhibition, and reduced chromatin accessibility in the vicinity of downstream promoters. Overall, our model is consistent with productive transcription from upstream promoters triggering downstream promoter activation in the presence of U1 snRNP by destabilizing nucleosomes and promoting promoter escape at downstream promoters.

overall_design: CUT&RUN-seq was performed for 4 targets: H3K4me3, Total RNA Polymerase II, Ser2-Phosphorylated RNA Polymerase II, and Ser5-Phosphorylated RNA Polymerase II. For each target, six samples with two distinct experimental conditions were investigated: 3 biological replicate sets of cells treated with a Control Antisense Morpholino (Control AMO) and 3 biological replicate sets of cells treated with a U1 Antisense Morpholino (U1 AMO).


title: U1 snRNP regulates alternative promoter activity by inhibiting premature polyadenylation [RNA-seq]

summary: Transcription and splicing are inherently intertwined. Accumulating evidence support a role of splicing factors in mediating this coupling. U1 small nuclear ribonucleoprotein particle (U1 snRNP), a key splicing factor, acts as the initial building block of the spliceosome, interacting with nascent pre-mRNA at 5' splice sites. In addition to its role in splicing, U1 snRNP is crucial for preventing premature cleavage and polyadenylation, enabling long-distance transcription elongation. Here, we show that U1 snRNP can regulate the usage of alternative promoters through its role in inhibiting premature polyadenylation. Using antisense oligonucleotides to inhibit U1 snRNP, we first observed a markedly decrease in downstream promoter activity at the newly synthesized RNA level. Interestingly, U1 snRNP inhibition selectively impacts downstream promoters of genes featuring premature polyadenylation sites located between two promoters. Overexpressing a wild-type U1 snRNP or a gene-specific U1 snRNP designed to inhibit premature polyadenylation sites restores downstream promoter activity. Conversely, introducing a premature polyadenylation site between two promoters reduces downstream promoter activity. Exploring the underlying molecular mechanisms, we identified a substantial decrease in serine 5 phosphorylation levels in newly recruited RNA polymerase II at downstream promoters following U1 snRNP inhibition, and reduced chromatin accessibility in the vicinity of downstream promoters. Overall, our model is consistent with productive transcription from upstream promoters triggering downstream promoter activation in the presence of U1 snRNP by destabilizing nucleosomes and promoting promoter escape at downstream promoters.

overall_design: Five samples with two distinct experimental conditions were investigated by RNA-seq : 2 biological replicate sets of cells treated with a Control Antisense Morpholino (Control AMO) and 3 biological replicate sets of cells treated with a U1 Antisense Morpholino (U1 AMO).


title: Genome-wide analysis of gene regulatory networks in chickens reveals dynamic temporal changes in retinal signaling cascade underlying compensation to lens-imposed optical defocus [control]

city: New York

first: Andrei

middle: V.

last: Tkatchenko

state: NY

department: Edward S. Harkness Eye Institute

institute: Columbia University

summary: During postnatal development, the optical geometry of the eye is refined through a process called emmetropization. During eye emmetropization, positive optical defocus inhibits eye growth whereas negative optical defocus accelerates it. Increased exposure to negative optical defocus leads to the development of myopia. Although several studies investigated gene regulatory networks underlying retinal response to optical defocus, temporal changes that occur during ocular response to optical defocus are poorly understood. Here, we performed a genome-wide analysis of the retinal gene regulatory networks underlying optical-defocus-induced myopia using massive parallel RNA sequencing (RNA-seq) in chickens exposed to negative optical defocus for 1, 3 and 6 days. Our analysis revealed large-scale dynamic temporal changes in the retinal signaling pathways involved in the eye’s response to negative optical defocus. We found that different sets of pathways and biological functions were involved in the early, sustained and delayed response to optical defocus causing myopia. These data refine signaling pathways that can be targeted for myopia control and provide a framework for the development of new treatment options for myopia.

overall_design: Analysis of mRNA expression in the retina of a control group of chickens during a 6 day period

first: Tatiana

middle: V


title: Genome-wide analysis of gene regulatory networks in chickens reveals dynamic temporal changes in retinal signaling cascade underlying compensation to lens-imposed optical defocus [6d]

overall_design: Analysis of mRNA expression in the retina of chickens in which myopia was induced with -10D lenses for 6 days


title: Genome-wide analysis of gene regulatory networks in chickens reveals dynamic temporal changes in retinal signaling cascade underlying compensation to lens-imposed optical defocus [lens induced]

overall_design: Analysis of mRNA expression in the retina of a group of chickens with lens-induced myopia (-10D lenses) during a 6 day period


title: Genome-wide analysis of gene regulatory networks in chickens reveals dynamic temporal changes in retinal signaling cascade underlying compensation to lens-imposed optical defocus


title: ILC3s-derived RANKL contributes to tuft cell hyperplasia and anti-helminth immunity

city: Beijing

first: Xiaohuan

last: Guo

address: Hai Dian

department: Institute for Immunology

institute: Tsinghua University

summary: Intestinal tuft cells are reported to orchestrate parasite type 2 immunity through producing IL-25 and LTC4. Meanwhile, type 2 cytokines IL-13 and IL-4 can induce tuft cell hyperplasia from intestinal stem cells during helminth infection. Here, using intestinal organoids culture, we show that RANKL synergizes with both IL-13 and IL-4 to enhance tuft cell expansion. Genetic mouse models revealed that RANK-RelB axis in intestinal epithelial cells (IECs) is required for optimal tuft cell-ILC2 circuit activation during helminth infection. Mechanistically, RANKL enhances IL-13-activated IL-4RA/STAT6 signaling in IECs, promoting tuft cell differentiation. Using genetic mouse models, we further demonstrated that ILC3s-derived RANKL is indispensable for optimal tuft cell hyperplasia during helminth infection. The scRNA-seq data revealed that N. brasiliensis infection will modulate ILC3 subsets distribution and RANKL expression.

overall_design: We cultured the intestinal organoids from Vil-creERT2; Rankfl/fl mice with or without 4-OHT (termed as WT and KO respectively). To explore the signaling pathways modulated by RANKL, we further treated the WT and KO organoids with IL-13 and with or without RANKL for 4 days. Then the intestinal organoids were applied for bulk RNA sequencing. To explore the adaptations of ILC3s during helminth infection, intestinal lamina propria leukocytes(LPL) from naïve mice or N. brasiliensis-infected mice were isolated and applied for single-cell RNA sequencing. Three subsets of ILC3s were identified and the transcriptional transitions of ILC3s from naïve state to N. brasiliensis infection were analyzed.

first: Hongkai

last: Xu

first: Yibo


title: Genome-wide analysis of gene regulatory networks in chickens reveals dynamic temporal changes in retinal signaling cascade underlying compensation to lens-imposed optical defocus [3d]

overall_design: Analysis of mRNA expression in the retina of chickens in which myopia was induced with -10D lenses for 3 days


title: FUS regulates the alternative splicing of cell proliferation genes related to atherosclerosis in human umbilical vein endothelial cells

city: Wuhan

first: Dong

last: Chen

state: Hubei

address: 388 GaoXin 2nd Road, East Lake Hi-Tech Development Zone

department: Center for Genome Analysis

institute: ABLife, Inc.

summary: FUS is an RNA binding protein that plays an important role in various cellular processes including RNA splicing, DNA repair and transcriptional regulation. However, the RNA binding capacity of FUS in atherosclerosis is unclear.we knocked down FUS with siRNA to further study the overall transcriptional level and select alternative splicing (AS) of FUS regulation in human umbilical vein endothelial cells (HUVECs) by RNA sequencing. The qRT-PCR strategy was used to validate FUS-modulated genes.Knockdown of FUS had significant effects on gene expression in HUVECs. Knock-down of FUS resulted in 200 differentially expressed genes (DEGs) that were highly related to apoptotic process, signal transduction, multicellular organism development, cell adhesion and regulation of transcription, DNA-templated pathways. Importantly, FUS extensively regulated 2870 alternative splicing events with a significant difference. Functional analysis of its-modulated alternative splicing genes revealed they were highly enriched in cell cycle, cell population proliferation and G2/M transition of mitotic cell cycle pathways. The results of qRT-PCR were consistent with the RNA-seq analysis.

overall_design: We knocked down FUS with siRNA to further study the overall transcriptional level and select alternative splicing (AS) of FUS regulation in human umbilical vein endothelial cells (HUVECs) by RNA sequencing

first: Jianjun

last: Hou

first: Shaobing

last: Yang

first: Ying

first: Ning

last: Yan


title: RNA sequencing of neuroblastoma cells treated with selinexor or with XPO1 knockdown

city: bethesda

first: Jack

last: Shern

state: MD

address: 10 Center drive

institute: NCI

summary: The study objective was to profile the transcriptomic changes in neuroblastoma IMR5 cells following treatment with selinexor for 24 hours or XPO1 knockdown at 72 hours.

overall_design: Examination of the effect of selinexor treatment and XPO1 knockdown in the neuroblastoma cell line IMR5.

first: Rosa

last: Nguyen

first: Carol

last: Thiele


title: IGF2BP3 may contributes to lung tumorigenesis by regulating the alternative splicing of PKM.


title: Expression data from heart ventricle and brain cortex of adult (2 month) tatd+/+ and tatd-/- C57/B6 mice

city: Lleida

first: Daniel

last: Sanchis

address: Av. Rovira Roure, 80

department: Ciències Mèdiques Bàsiques

institute: Universitat de LLeida - IRBLleida

summary:
TatD is part of the E coli TatABCD operon with functions in protein secretion. E coli TatD is not involved in protein transport. E coli TatD could be involved in DNA degradation and/or protein quality control. C elegans TatD is involved in embryo development. P falciparum TatD could be involved in virulence. No data on mammalian TatD is published
We used microarrays to analyze the gene expression changes induced by Tatd gene deletion in the heart ventricle and brain cortex of adult wild type (tatd+/+) and TatD-deficient (tatd-/-) mice.

overall_design: cardiac ventricles and brain cortex were obtained from 3 males and 3 females per genotype (tatd+/+, tatd-/-). Total RNA was extracted using the RNeasy Mini Kit (Qiagen) and retro-transcribed. The microarray plate used was the Mouse Clariom S HT array (Applied Biosystems, ThermoFisher, 902971).

first: Ricardo

last: Gonzalo


title: IGF2BP3 may contributes to lung tumorigenesis by regulating the alternative splicing of PKM [RNA-seq]

summary: RNA binding proteins (RBPs) play a key role in genome regulation. Here we report the post-transcript regulation of IGF2BP3, which belongs to the insulin-like growth factor 2 mRNA binding protein family. We used iRIP-seq and RNA-seq to analyze the transcript regulation and alternative splicing on IGF2BP3 treated with overexpression cells and control. Overexpressed IGF2BP3 has broadly increased genes expression which involved in G-protein coupled receptor signaling pathway, positive regulation of cell proliferation and signal transduction. IGF2BP3 regulated alternative splicing of multiple genes mainly clustered at response to hypoxia, negative regulation of transcription, and embryonic development. This study first provides alternative splicing analysis on transcription level of IGF2BP3 regulation, which laid the foundation for later research on IGF2BP3 critical functions

overall_design: transcription analysis of IGF2BP3 overexpression and control in A549 cells

first: Yin

last: Tiejun

first: Huang

last: Xueqing


title: Prim-O-glucosylcimifugin Attenuates TGF-β-Induced Fibrosis via MAPK Pathway Inhibition and ECM Remodeling in Intestinal Fibroblasts

status: Public on May 18 2025

city: Daejeon

first: Seokwon

last: Kim

address: 99, Daehak-ro, Yuseong-gu

country: South Korea

institute: Chungnam National University

summary: Background: Intestinal fibrosis is a major complication of inflammatory bowel disease (IBD), particularly Crohn’s disease, and often necessitates surgical intervention due to stricture formation. Despite progress in anti-inflammatory therapies, effective anti-fibrotic treatments remain lacking. Objective: This study evaluated the anti-fibrotic potential and underlying mechanisms of Prim-O-glucosylcimifugin (POG), a natural chromone derivative, in human intestinal fibroblasts. Methods: Fibrosis was induced in human intestinal fibroblast cell lines and primary fibroblasts by TGF-β1 (2 ng/mL). Cells were treated with POG, and fibrotic marker expression was assessed by immunofluorescence, qPCR, and Western blot. MMP1 activity and fibroblast migration were analyzed. Transcriptomic and integrative network analyses were performed to elucidate molecular mechanisms. Results: POG significantly suppressed TGF-β1-induced fibroblast activation, downregulating fibrotic markers (α-SMA, fibronectin, collagen I/III, N-cadherin) and inhibiting Smad and MAPK signaling. POG also promoted ECM degradation by upregulating MMP1 and suppressing TIMP1. Transcriptomic data confirmed regulation of pathways involved in ECM remodeling and MAPK signaling. POG displayed no cytotoxicity in intestinal epithelial cells.  Conclusion: POG mitigates intestinal fibrosis by dual inhibition of TGF-β/Smad and MAPK pathways and by enhancing ECM degradation through selective modulation of the MMP1-TIMP1 axis. These findings support POG as a promising therapeutic candidate for intestinal fibrosis in IBD.

overall_design: Comparative gene expression profiling analysis of RNA-seq data for CCD-18co cells by TGF-β and TGF-β+POG 30uM

first: Han Na

last: Kang

first: Sang-Min

last: Park

first: Ami

last: Lee

first: Seo-Young

first: Youn-Hwan

last: Hwang


title: Genome-wide analysis of gene regulatory networks in chickens reveals dynamic temporal changes in retinal signaling cascade underlying compensation to lens-imposed optical defocus [1d]

first: Andrei

last: Tkatchenko

overall_design: Analysis of mRNA expression in the retina of chickens in which myopia was induced with -10D lenses for 1 day

first: Tatiana


title: CARM1 is an integral component of the NuRD chromatin remodeling complex (RNA-Seq)

city: Ganzhou

first: Wenjuan

last: Zhang

state: Jiangxi

address: No. 23, Qingnian Road

department: First Affiliated Hospital

institute: Gannan Medical University

summary: The nucleosome remodeling and deacetylase (NuRD) complex is a large multi-subunit complex that couples ATP-dependent chromatin-remodeling and histone deacetylase activities. Emerging evidence suggested that the NuRD complex is prevalently associated with gene transcriptional activation, but little is known about the underlying molecular mechanisms. Here, we reported that the transcriptional coactivator CARM1 is an integral component of the NuRD complex, expanding the activities of the NuRD complex to include arginine methylation. CARM1-associated NuRD binds and activates a large cohort of genes, including those implicated in cell cycle control, to facilitate the G1/S transition. This gene activation process requires CARM1 to catalyze methylation of histone 3 and a key subunit of the NuRD complex, GATAD2A/2B. The biological significance of this gene activation mechanism is underscored by the coordinated expression of both CARM1 and NuRD in breast cancers, which proves to be critical for breast cancer cell growth in vitro and tumorigenesis in vivo. These findings reveal a gene activation program that requires the dual specificity established by CARM1 on chromatin and a key chromatin remodeler.

overall_design: RNA-seq performed in this study was designed to understand the molecular mechanisms underlying CARM1/NuRD in gene transcription activation.

first: Wen

last: Liu

first: Ming-Feng

last: Huang

first: Wen-Juan

first: Xu

last: Pan


title: RNA sequencing of the silenced gene CYTH4 in acute myeloid leukemia cell lines

city: ganzhou

first: qiu

last: xiaofen

address: No. 16, Meiguan Avenue

institute: ganzhou People's Hospital

summary: In silico analysis revealed an elevated expression of cytohesin-4 (CYTH4) in acute myeloid leukemia (AML) cells, correlating with a poorer prognosis for AML patients. However its role in AML is not fully understood. Our study using loss-of-function assays identified CYTH4 as an oncogene promoting leukemogenesis. Silencing CYTH4 in MV4-11 and THP-1 cells reduced cell proliferation, colony formation, and induced apoptosis and cell cycle arrest at G0/G1, whereas overexpression had no significant impact. CYTH4 silencing also increased chemosensitivity to cytarabine. In a THP-1 xenograft model, CYTH4 silencing slowed AML progression and reduced leukemic cell homing and infiltration. Mechanistically, CYTH4 silencing inhibited PI3K/AKT pathway by lowering PIK3R5 and decreased ARF6-GTP levels, as confirmed by pull-down assays. Overexpression of PIK3R5 and AKT activation via SC-79 successfully countered the cellular dysfunctions from CYTH4 silencing. Thus, CYTH4 may play a role in AML progression, and targeting its pathway could be a promising anti-leukemic treatment strategy.

overall_design: After treating the cell lines MV4-11 and THP-1 with SHRNA targeting CYTH4, total RNA of the cell lines was collected for RNA-SEQ analysis.


title: CARM1 is an integral component of the NuRD chromatin remodeling complex

overall_design: ChIP-seq performed in this study was designed to understand the molecular mechanisms underlying CARM1/NuRD in gene transcription activation.


title: IGF2BP3 may contributes to lung tumorigenesis by regulating the alternative splicing of PKM [RIP-seq]

first: Dong

last: Chen

overall_design: RIP-seq analysis of IGF2BP3 IP versus input in A549 cells.


title: U1 snRNP regulates alternative promoter activity by inhibiting premature polyadenylation [ATAC]

first: Ana

last: Fiszbein

overall_design: Six samples with two distinct experimental conditions were investigated by ATAC-seq : 3 biological replicate sets of cells treated with a Control Antisense Morpholino (Control AMO) and 3 biological replicate sets of cells treated with a U1 Antisense Morpholino (U1 AMO).


title: Genome-wide profiling of tRNA modifications reveal the presence of divergent signatures in Plasmodium falciparum

first: Sherwin

last: Chan

address: Solnavagen 9

type: Non-coding RNA profiling by high throughput sequencing

type: Methylation profiling by high throughput sequencing

summary: tRNAs are known to be extensively decorated with various nucleotide modifications, which can modulate the biological properties of tRNAs, such as promoting translation efficiency or fidelity, influencing codon preference and stabilizing tertiary structure of tRNAs. Dynamic alteration of the tRNA modifications, particularly under stress, are conserved gene regulatory mechanisms employed by cells across the kingdoms of life. The malaria-causing Plasmodium falciparum, which has a highly AT-biased genome, is reliant on a non-redundant set of tRNA genes to decode distinct and codon-skewed transcriptomes across its developmental stages. This genomic feature highlights the regulatory potential of tRNA modifications and warrants studies on how the tRNA epitranscriptome can impact gene regulatory function in this parasite. However, systematic studies of tRNA modifications in P. falciparum remain sporadic. In this study, we present a sequencing-based analysis of tRNA modifications in P. falciparum through optimizing the TGIRT-tRNA sequencing approach. The optimized protocol significantly reduces reverse transcription (RT) stop-induced short reads and enhances full-length cDNA synthesis, enabling the identification and stoichiometric estimation of a select nucleotide modifications at single-base resolution. We were able to identify seven types of conserved tRNA modifications and discovered two non-canonical signatures at A59 and U73 positions on specific nuclear-encoded tRNAs, which provides new insights into previously unreported modification sites. Our findings further reveal the dynamic nature of tRNA modifications during stage progression and under stress conditions.

overall_design: Plasmodium falciparum in vitro cultures were grown to different developmental stages and subjected to antimalarial treatment, the tRNA modification profiles were characterzied using tRNAseq

first: Qian

last: Li

first: Ylva

last: Veith

first: Ola

last: Larsson


title: Identification and Targeting of Regulators of SARS-CoV-2-Host interactions in the Airway Epithelium [scRNA-Seq]

first: Lorenzo

last: Tomassoni

address: 1130 St Nicholas Avenue

summary: The conducting airway epithelium is the first line of defense in the respiratory tract against pathogens and a prime site of SARS-CoV-2 viral entry, serving to maintain a high viral load during lung infection. The impact of SARS-CoV-2 infection in the respiratory epithelium has been extensively studied.  However, still less is known about the regulators of SARS-Cov-2-induced programs that facilitate infection and viral replication in distinct human airway epithelial cell populations, such as basal, secretory, and multiciliated cells.  Here, we used SARS-CoV-2-infection of human airway epithelial organotypic cultures, single cell transcriptomics, large FDA-approved drug perturbation profiles combined with Master Regulator analysis to identify host cell defense and response pathways determinants of viral infection

overall_design: Primary human airway epithelial cells were isolated from de-identified adult human transplant organ donors and were grown in PnuemaCult ALI (media was changed every other day until day 21). ALI-differentiated cells at day 21 were inoculated on the apical surface by SARS- CoV-2 and were allowed to grow for 1, 3, and 6 days post infection (dpi), prior to be submitted for Single-Cell RNA Sequencing.

first: Brooke

last: Dirvin

first: Heeju

last: Noh

first: Danting

last: Cao

first: Yizhou

last: Zhou

first: Xiangye

last: Ke

first: Jun

last: Qian

first: Sonia

last: Jangra

first: Michael

last: Schotsaert

first: Adolfo

last: Garcia-Saestre

first: Charles

last: Karan

first: Andrea

last: Califano

first: Wellington

last: Cardoso


title: Identification and Targeting of Regulators of SARS-CoV-2-Host interactions in the Airway Epithelium [PlateSeq]

overall_design: Primary Human Airway Epithelial cells were cultured and prepared for a large PlateSeq drugs perturbational screening (10 96-well plates, 441 FDA-approved drugs in total)


title: EZH2 loss promotes gastric squamous cell carcinoma [CUT&Tag]

first: Ailing

last: Zhong

summary: Gastric Squamous Cell Carcinoma (GSCC) is a rare subtype of gastric cancer with unique histopathology while gastric adenosquamous carcinoma (GASC), which partially shares features of GSCC, is more frequent. Both GSCC and GASC have poor prognosis but the molecular mechanisms underlying these malignancies are unknown. Here, we performed genomics analyses of eleven GSCC samples and found that epigenetic regulation genes were among the most frequently mutated genes. Among them was Enhancer of zeste homolog 2 (EZH2), which was also significantly downregulated in GASC, compared to gastric adenocarcinoma (GAC). Ezh2 loss led to squamous feature both in gastric organoids in vitro and in vivo. Importantly, Ezh2 deficiency, together with Trp53 and Pten loss, both of which were also frequently mutated in GSCC, gave rise to full-blown GSCC in mice. Mechanistically, we found that Ezh2 could repress the expression of Transcription factor AP-2 gamma (Tfap2c), a transcription factor with the ability to initiate epidermal squamous differentiation, through H3K27 methylation. Disruption of Tfap2c reversed Ezh2 loss-driven GSCC into GAC and reduced its resistance to chemo treatment. Our study revealed the mechanisms of GSCC/GASC tumorigenesis and shed light on future treatment.

overall_design: Gastric organoids and various mouse models of gastric cancer were applied to investigate the functions of EZH2 in GSCC tumorigenesis. Histological assays and transcriptome profiling were used to analyze the properties of GSCC models with Ezh2 deficiency. Multi-omics analyses, including RNA-seq and CUT&Tag-seq , were performed to identify the molecular mechanisms of EZH2 loss in GSCC, which were further validated with in vitro and in vivo functional assays.

first: Mengsha

last: Zhang


first: Wenjuan

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

overall_design: Refer to individual Series


title: EZH2 loss promotes gastric squamous cell carcinoma [RNA-seq]


title: Identification and Targeting of Regulators of SARS-CoV-2-Host interactions in the Airway Epithelium

first: Yizhuo

first: Xiangyi

last: Garcia-Sastre


title: Ovarian transcriptome sequencing (scRNA-seq and RNA-seq) of 6 and 9-month-old mice fed black rice, white brown rice and polished rice

city: WuHan

first: Yi-Xuan

last: Tu

state: HuBei

address: 1 Shizishan Rd

department: College of Life Science and Technology

institute: Huazhong agricultural university

summary: Mice were fed black rice, white brown rice and polish rice to compare the effects of different diets on ovarian aging

overall_design: Starting at 2 month-old, the mice were given three diets, killed at 6 months and 9 months, and the ovaries were taken for 10Xgenomics and bulk-seq.

first: Zhen-Xia

middle: T

last: Chen

first: Ling

last: Wang

first: Dan-Yang


title: FTDC1/2, oocyte-specific cofactors of DNMT1 required for epigenetic regulation and embryonic development (Bisulfite-Seq)

city: Nanjing

first: Jiashuo

last: Li

address: 101Longmian Avenue, Jiangning District, Nanjing 211166, P.R. China

institute: Nanjing Medical University

summary: In order to obtain genome-wide profiles, base-resolution methylomes of oocytes, 4-cells and blastocysts were generated using the bisulfite sequencing (BS-seq) method for few samples. We find that global loss of DNA methylation during preimplantation development in Ftdc1-/-and Ftdc2-/- mice. Such a loss of methylation upon Ftdc1 or Ftdc2 inactivation is truly global and occurs across all chromosomes and genomic features examined, such as exon, intron, transposon and etc. To refine the analysis, we identified 7,311 and 6,208 hypomethylated differentially methylated regions (hypo-DMRs) and no hypermethylated DMRs (hyper-DMRs) in Ftdc1- and Ftdc2-null blastocyst compared to WT, respectively.  To test whether FTDC1/2 deficiency and the observed global hypomethylation have an impact on transcriptional activity, we conducted RNA-sequencing in WT and Ftdc1- or Ftdc2-null blastocysts. 1,886 and 1,073 differentially expressed genes were identified in Ftdc1-/-(up 945, down 941) and Ftdc2-/- embryos (up 945, down 941). Gene ontology (GO) analysis showed that these DEGs are primarily enriched in gastrulation, autophagy, adhesion, and immune system-related pathways.   To assess the potential effects of FTDC1/2 deficiency on histone modifications, our genome-wide profiles of H3K9me3 in blastocysts revealed that FTDC1/2 depletion results in the massive loss of H3K9me3. In contrast, H3K9me3 was correspondingly reduced in those hypo-DMRs in Ftdc1-/- and Ftdc2-/- embryos.

overall_design: Methylation profiling by high throughput sequencing

first: Congyang

first: Siyu

last: Du

first: Qiang


title: FTDC1/2, oocyte-specific cofactors of DNMT1 required for epigenetic regulation and embryonic development

overall_design: Transcriptome profiling by high throughput sequencing


title: SLAM-seq reveals the promotive role of NDRG1 in Fusobacterium nucleatum-induced Tumorigenesis in Colorectal Cancer.

status: Public on May 17 2025

city: Guangzhou

first: Hui

state: GuangDong

address: 190 Kaiyuan Avenue, Huangpu District

institute: GUANGZHOU INSTITUTES OF BIOMEDICINE AND HEALTH, CAS

summary: We report the characterization of transcript dynamics in human colorectal cancer HCT116 cells during Fusobacterium nucleatum infection using thiol-linked alkylation for the metabolic sequencing of RNA (SLAMseq).

overall_design: RNA-seq profiling of HCT116 cells in the condition of infection (Fn) and uninfection (noFn) at a 2 hour of 4sU labeling (+4sU) or unlabeling (-4sU)

first: SongHe

last: Guo


title: Large-scale, quantitative proteomics reveals key proteins required for planarian regeneration initiation

city: 杭州市

first: li

last: yucong

state: 浙江省

address: 浙江省杭州市西湖区墩余路600号西湖大学云谷校区E8120

institute: 西湖大学生命科学学院博士研究生

summary: Multi-omics studies are increasingly used to decipher the mechanisms underlying tissue regeneration. However, the use of proteomics for such studies has been limited due to the high cost and relatively low throughput and reproducibility. The genes required for planarian regeneration have primarily been identified based on changes in mRNA transcripts; previous studies have not addressed the possibility of protein upregulation prior to detectable increases in transcript abundance during the early stages of planarian regeneration. Here, we used in-depth high-throughput proteomics approaches to analyze the model planarian Schmidtea mediterranea during regeneration and discovered 13 proteins that are essential regulators of key regeneration steps. Two of these proteins, Troponin T and MRPL18, are key regulators of regeneration initiation and showed increases in protein abundance prior to upregulation at the mRNA level. Extensive comparisons between proteomic and transcriptomic datasets suggested the critical mechanisms beyond the transcriptional level, such as the translational and post-translational levels. In summary, this study revealed key regulators of regeneration in a model organism; furthermore, it established an adaptable spectral library and comprehensive proteomics datasets, enabling future in-depth and multi-omics analyses of planarian biology.

overall_design: mRNA of planarians three days post lethal irradiation treatment vs wide type control

first: Kai

last: Lei


title: Targeting circulating mechanoresponsive monocytes and macrophages to reduce fibrosis

city: Tucson

first: Kellen

state: AZ

address: 1501 N Campbell Ave

department: Surgery

institute: University of Arizona

summary: We performed single-cell RNA sequencing on skin, wounded tissue, or wounded tissue subjected to mechanical strain. Wounds could be treated with focal adhesion kinase inhibitor (FAKI) hydrogels or in mice with FAK knocked out in the myeloid cells

sample_organism:
Homo sapiens
Mus musculus

platform_organism:
Homo sapiens
Mus musculus

overall_design: scRNA-seq was performed on murine cells collected from skin, scar, or wounds. Cells labeled as GFP+ were isolated and sequenced to analyze cells in the circulation that hone to the wound upon treatment.

first: Geoffrey

middle: C

last: Gurtner


title: Mitochondrial fusion controls the development of specialized mitochondrial structure and metabolism in rod photoreceptor cells

city: Madison

first: Ryo

last: Hagimori

state: WI

address: 425-G Henry Mall

department: Department of Medical Genetics

institute: University of Wisconsin-Madison

summary: Mitochondria are dynamic organelles that undergo continuous morphological changes, yet exhibit unique, cell-type-specific structures. In rod photoreceptor cells of the retina, these structures include elongated mitochondria in the inner segments and a distinct, large, circular mitochondrion in each presynaptic terminal. The mechanisms underlying the establishment and maintenance of these specialized mitochondrial morphologies, along with their functional significance, are not well understood. Here, we investigate the roles of mitochondrial fusion proteins mitofusin 1 (MFN1) and mitofusin 2 (MFN2) in shaping these structures and maintaining photoreceptor cell health. Rod photoreceptor cell-specific ablation of MFN1 and MFN2 resulted in mitochondrial fragmentation by one month of age, suggesting that mitochondrial fusion is essential for the development of photoreceptor cell-specific mitochondrial structures. Notably, the layer structures of the retina examined by light microscopy appeared unaffected at this age. Following this time period, significant photoreceptor cell degeneration occurred by three months of age. Furthermore, we showed that impaired mitochondrial fusion perturbed the balance of proteins involved in glycolysis, oxidative phosphorylation (OXPHOS), and β-oxidation, highlighting the critical role of mitochondrial fusion in ensuring the proper levels of proteins necessary for optimal energy metabolism. Additionally, we identified upregulation of cellular stress pathways such as endoplasmic reticulum (ER) stress and unfolded protein response (UPR), which arise in response to energy deprivation, and cytoprotective biosynthetic pathways mediated by CCAAT/enhancer-binding protein gamma (C/EBPγ) and mammalian target of rapamycin complex 1 (mTORC1) signaling. In summary, our findings indicate that mitochondrial fusion through MFN1 and MFN2 is vital for the development of unique mitochondrial structures and proper energy production, underscoring the fundamental importance of mitochondrial dynamics in photoreceptor cell function and survival.

overall_design: RNA-seq profiles of neutal retina from one-month-old control (cre-/-) mice and rod-specific double cKO (Rho-Cre/Mfn1flx/flx/Mfn2flx/flx) mice

first: Michael

last: Landowski

first: Vijesh

last: Bhute

first: Tetsuya

last: Takimoto


title: Gene Expression Modulation by Ultrasound-Responsive Biocatalytic 3D Scaffolds for Controlled Osteosarcoma Cell Elimination and Rat Cranial Bone Regeneration

city: Chengdu

first: Xiao

last: Rong

state: None Selected

address: Guoxuexiang 37

institute: West China Hospital, Sichuan University

summary: Sonodynamic therapy (SDT) offers high efficiency and controllable precision in tumor eradication, while smart enzyme-mimetic materials enable pH-dependent switching between ROS generation and scavenging. Herein, we present HS-ICTO, a 3D-printed scaffold with ultrasound-triggered activation and microenvironment-responsive enzyme-mimetic properties, designed for spatiotemporally controlled therapeutic applications. The HS-ICTO scaffold synergistically enhances tumor elimination via TME-responsive ROS generation coupled with SDT effects, while switching to ROS scavenging in physiological conditions to protect stem cells. We conducted RNA sequencing on human osteosarcoma 143B cells treated with conventional scaffold (HS), HS-ICTO, and HS-ICTO + ultrasound (US), and performed comparative transcriptomic analysis of tissue cells in rat calvarial defect repair models implanted with HS versus HS-ICTO scaffolds.

sample_organism:
Homo sapiens
Rattus norvegicus

platform_organism:
Homo sapiens
Rattus norvegicus

overall_design: To investigate the synergistic capacity of SDT and enzyme-mimetic ROS generation for tumor cell eradication, we seeded 143b cells on HS and HS-ICTO scaffolds and applied US irradiation for HS-ICTO + US group. After treatment, the RNA-seq was conducted. To investigate the ROS-scavenging capacity of HS-ICTO in safeguarding bone repair processes, we established rat calvarial defect models implanted with HS and HS-ICTO scaffolds. Four weeks post-implantation, the scaffolds were harvested, and RNA from intra-scaffold tissue cells was extracted for RNA-seq analysis

first: Rong

last: Xiao

last: Sutong


title: Effect of Candida albicans SC5314 under treatent of NT-a9, fluconazole or drug-free control.

city: Shanghai

first: Shuo

last: Zhu

address: No. 500 of Zhennan Road

institute: Tongji University

summary: Under treatment of 4×MIC, the NT-a9 group has more differentially expressed genes (DEGs) than the FLC group, indicating NT-a9 caused more significant transcriptional changes than FLC (Figure S4B). The KEGG pathways enrichment analysis of DEGs showed that NT-a9 imposed a greater interference on sterol biosynthesis (Figure S4C). Notably, key genes involved in ergosterol biosynthesis, such as ERG1, ERG2, ERG3, ERG5, ERG6, ERG7, ERG9, ERG10, ERG11, ERG12, ERG13, ERG20, ERG24, ERG25, ERG26, ERG27, ERG28, ERG251, HMG1, IDI1 and NCP1, demonstrated markedly upregulated expression levels in NT-a9-treated group, compared to both control and FLC-treated groups (Figure S4D). These findings establish ergosterol biosynthesis inhibition as the primary mechanism underlying NT-a9's antifungal activity. In addition, KEGG pathway enrichment analysis revealed that NT-a9 profoundly impacts multiple essential metabolic pathways in C. albicans: Amino acid metabolism, including biosynthesis and catabolism of lysine, branched-chain amino acids (valine, leucine, isoleucine), histidine, and aromatic amino acids (phenylalanine, tyrosine, tryptophan); Energy metabolism, particularly pyruvate metabolic pathways; Cell proliferation processes, including DNA replication and cell cycle regulation (Figure S4C). Notably, NT-a9 significantly upregulated the terpenoid backbone biosynthesis pathway, the critical upstream precursor of sterol biosynthesis (Figure S4C). These findings suggest that NT-a9's antifungal mechanism extends beyond conventional sterol synthesis inhibition, potentially exerting multi-target effects that disrupt fundamental fungal cellular processes, ultimately leading to extensive secondary cellular damage.

overall_design: The overnight-cultured SC5314 was adjusted to 2×10⁶ cells/mL and incubated with or without NT-a9 (4×MIC) or FLC (4×MIC) at 30°C with shaking at 200 rpm for 12 hours, with three replicates per group.

first: Yuanying

last: Jiang

first: Lu

last: Gao


title: S100A8/A9-related myocardial injury after non-cardiac surgery: RNA sequencing analysis in a novel mouse model

city: Sapporo

first: Makishi

last: Maeda

address: South1 West 16 291

department: Anesthesiology

country: Japan

institute: Sapporo Medical University School of Medicine

summary: The aim of this study was to develop a new mouse model of myocardial injury after non-cardiac surgery (MINS) and to elucidate its pathophysiology. Male C57BL/6 mice underwent abdominal surgery under sevoflurane anesthesia, and myocardial samples were collected at multiple time points post-surgery. Gene expression profiling using RNA sequencing data from these samples was performed to investigate the molecular changes associated with MINS.

overall_design: RNA-seq profiling of mouse heart tissue from male C57BL/6 mice collected at multiple time points post-abdominal surgery under sevoflurane anesthesia


title: Analysis of gene expression in TNF transgenic mice

city: Rochester

first: Benjamin

last: Korman

address: 601 Elmwood Avenue, Box 695

institute: AIR

summary: Recently, we found that human TNF transgenic (TNF-Tg) mice died by 6-month from cardiopulmonary disease. Histological analysis showed that TNF-Tg mice were characterized by the pulmonary vascular and right ventricular pathology. This pathology closely mimics human connective tissue disease (CTD) associated pulmonary arterial hypertension (PAH). In this study, we aimed to investigate the gene expression in TNF-Tg lung using bulkRNA-seq technology.

overall_design: Lung was harvested from 4-month-old TNF-Tg and WT mice. Total RNA was extracted using QIAGEN Rneasy Plus Kits.

first: Gaochan

last: Wang


title: The impact of artificial unilateral cryptorchidism on spermatogenesis in cynomolgus monkeys viewed at single-cell resolution

first: Ji-Long

last: Liu

address: 483 Wushan Rd

institute: South China Agricultural University

summary: Comparative analysis of unilateral abdomen testis (UAT) and the contralateral scrotum testis (CST).

overall_design: We used the cynomolgus monkey as an animal model and generated a single-cell transcriptomic atlas of  unilateral abdomen testis (UAT) and the contralateral scrotum testis (CST).


title: Antibacterial Effect of Epidemic Prevention Sachets Essential Oil against Staphylococcus Aureus

city: WuXi

first: Guoshui

last: Tao

address: No. 8, Zhongnan West Road, Wuxi City, Jiangsu Province

institute: WuXi Traditional Chinese Medicine Hospital

summary: Staphylococcus aureus (S. aureus) is one of the most dominant human pathogen, responsible for a variety of chronic and severe infections. As a classic traditional Chinese medicine (TCM) formula, Epidemic Prevention Sachets have been used clinically for centuries to treat infectious diseases. The antimicrobial activity of the essential oil (EO) from Epidemic Prevention Sachets against the S. aureus has not been investigated. In this study, the EO was tested for its antimicrobial activity against S. aureus. We identified that the EOs has high activity against S. aureus. It showed higher activity than the known antibacterial drug combination of Penicillin streptomycin. The same results were demonstrated by transmission electron microscopy. The impact of the EO on transcription of genes from S. aureus was analyzed. SAOUHSC_01002, SAOUHSC_02444, SAOUHSC_00282 and SAOUHSC_00325, which are involved in cation transport (GO:0006812), were significantly affected by the essential oil as defined in the Gene Ontology Biological Process (GO BP), whereas SAOUHSC_00114 and SAOUHSC_03000, which are involved in the protein tyrosine kinase modulator pathway (K19420), were significantly enriched in the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway. Analysis of clusters of orthologous groups (COG) found that there are differences in multiple metabolic pathways, mainly including secondary biosynthesis metabolism, biofilm related genes and energy metabolism. Our study indicates that the essential oil from Epidemic Prevention Sachets is an effective herbal formula against S. aureus.

overall_design: The uploaded data consists of six samples divided into two groups, with three replicates per group.

first: Chenlu

last: Huang

first: Tianhao

first: Lingjing

last: Kong

first: Shu

last: Lu

first: Linghao


title: Parallel gene expression changes in ventral midbrain dopamine and GABA neurons during normal aging

city: Oklahoma City

first: Ana Luiza

last: Drumond-Bock

state: OK

address: 825 NE 13th St.

department: Aging & Metabolism Research Program

institute: Oklahoma Medical Research Foundation

summary: The consequences of aging can vary dramatically between different brain regions and cell types. In the ventral midbrain, dopaminergic neurons develop physiological deficits with normal aging that likely convey susceptibility to neurodegeneration. While nearby GABAergic neurons are thought to be more resilient, decreased GABA signaling in other areas nonetheless correlates with age-related cognitive decline and the development of degenerative diseases. Here, we used two novel cell type-specific Translating Ribosome Affinity Purification models to elucidate the impact of healthy brain aging on the molecular profiles of dopamine and GABA neurons in the ventral midbrain. By analyzing differential gene expression from young adult (7-10 month) and old (21-24 month) mice, we detected commonalities in the aging process in both neuronal types, including increased inflammatory responses and upregulation of pro-survival pathways. Both cell types also showed downregulation of genes involved in synaptic connectivity and plasticity. Genes involved in serotonergic signaling were upregulated with age only in GABA neurons and not dopamine-releasing cells. In contrast, dopaminergic neurons showed alterations in genes connected with mitochondrial function and calcium signaling, which were markedly downregulated in male mice. Sex differences were detected in both neuron types, but in general were more prominent in dopamine neurons. Multiple sex effects correlated with the differential prevalence for neurodegenerative diseases such as Parkinson’s and Alzheimer’s seen in humans. In summary, these results provide insight into the connection between non-pathological aging and susceptibility to neurodegenerative diseases involving the ventral midbrain, and identify molecular phenotypes that could underlie homeostatic maintenance during normal aging.

overall_design: RNA-Seq profiling of cell specific (dopamine or GABA neurons), GFP-tagged, ribosomal complexes, in young and old NuTRAP-crosses (DAT;NuTRAP and VGAT;NuTRAP) mice.

first: Harris

middle: E

last: Blankenship

first: Kevin

middle: D

last: Pham

first: Kelsey

last: Carter

first: Willard

middle: M

last: Freeman

first: Michael

last: Beckstead


title: Chidamide and Anlotinib Synergistically Inhibit High Grade B-Cell Lymphomas via PI3K/AKT Signaling Pathway

city: Xiamen

first: jiazhen

last: lin

state: Fujian

address: No. 2000 of Xiang an East road

institute: Xiamen uniersity

summary: High-grade B-cell lymphoma with concurrent MYC and BCL2/BCL6 rearrangements (HGBL-DHL) presents a formidable challenge, often refractory and resistant to front-line immunochemotherapies, necessitating urgent exploration of novel therapeutic approaches. Herein, we unveiled a robust synergistic anti-lymphoma efficacy of chidamide and anlotinib against HGBL-DHL. The cooperative effect of cell proliferation inhibition, apoptosis induction, and cell cycle arrest were demonstrated in cell lines through Cell Counting Kit-8, and Annexin V/PI staining, respectively. Moreover, in an HGBL-DHL-xenografted mouse model, the combination therapy markedly reduced tumor burden without inducing fatal toxicity. Mechanistically, chidamide suppressed HDAC3, while anlotinib inhibited VEGFR2, leading to down-regulation of the PI3K/AKT signaling cascade. This dual suppression was by their synergistic effect. Collectively, our preclinical findings underscored the synergistic activity of chidamide and anlotinib combination against HGBL-DHL, warranting further clinical evaluation of this regimen for treating this challenging entity.

overall_design: TMD8 cell were treated with DMSO, chidamide, anlotinib and chidamide combined with anlotinib for 24h.The RNA from four groups of cells was extracted and subjected to RNA sequencing.

first: Jiazhen

last: Lin


title: An epigenetic clock for Xenopus tropicalis

city: Los Angeles

first: Matteo

last: Pellegrini

state: CA

address: 610 Charles E. Young Dr S

institute: University of California, Los Angeles

summary: DNA methylation clocks have been widely used for accurate age prediction, but most studies have been carried out on mammals. Here we present an epigenetic clock for the aquatic frog Xenopus tropicalis, a widely used model organism in developmental biology and genomics. To construct the clock, we collected DNA methylation data from 192 frogs using targeted bisulfite sequencing at genomic regions containing CpG sites previously shown to have age-associated methylation in Xenopus. We found highly positively and negatively age-correlated CpGs are enriched in heterochromatic regions marked with H4K20me3 and H3K9me3. Positively age-correlated CpGs are enriched in bivalent chromatin and gene bodies with H3K36me3, and tend to be proximal to lowly expressed genes. These epigenetic features of aging are similar to those found in mammals, suggesting evolutionary conservation of epigenetic aging mechanisms. Our clock enables future aging biology experiments that leverage the unique properties of amphibians.

overall_design: Targeted bisulfite sequencing of 187 adult Xenopus tropicalis frogs (hindlimb webbing skin punch tissue), and 5 whole tadpole Xenopus tropicalis. The animals were raised in aquatic tanks from birth, allowing measurement of the relationship between DNA methylation and age.

first: Ronan

last: Bennett

first: Marco

last: Morselli

first: Kseniya

last: Petrova

first: Leonid

last: Peshkin


title: Synaptic and Intrinsic Plasticity Mediated by CCK-type Signaling Coordinates Behavioral Changes During Motivational State Shifts

first: Guo

last: Zhang

address: Xianlin street 163

institute: Nanjing University

summary: Transitions from hunger to satiety involve multiple behavioral changes, including modulation and inhibition of feeding behavior. Cholecystokinin (CCK), a key satiety peptide in mammals, plays a critical role in these processes, though whether and how CCK might induce satiety via synaptic and intrinsic plasticity remain unclear. Here, we demonstrate that CCK acts as a classical brain-gut peptide in a protostome, mollusk Aplysia. CCK neurons, located in the gut, project centrally to release CCK at the site of the feeding pattern generator. In vivo, CCK reduced food intake, while in vitro, it shifted motor patterns towards egestion and inhibited feeding programs. Mechanistically, CCK primarily modulated the excitability of the egestive-promoting B20 interneuron and suppressed synaptic inputs to protraction motoneurons, thereby altering program type and inhibiting feeding program generation. These findings highlight the importance of both synaptic and intrinsic plasticity in specific circuit elements for implementing motivational shifts induced by satiety peptides.

overall_design: Smart single-cell sequencing of Aplysia B20 neuron and B34 neuron

first: Xue-Ying

last: Ding

first: Elena

last: Romanova

first: Cui-Ping

last: Liu

last: Barry

first: Alisha

last: Doda

first: Qian-Xue

last: Chen

first: Carrie

last: Reaver

first: Qing-Chun

last: Jin

first: Stanislav

middle: S

last: Rubakhin

first: Fan

last: Li

first: Yu-Fei

first: Yan-Sheng

last: Kan

first: Yu-Ling

first: Shi-Qi

last: Guo

first: Ying-Yu

last: Xue

first: Yu-Shuo

last: Mei

first: Ping

last: Fu

first: Ju-Ping

last: Xu

first: Rui-Ting

last: Mao

first: Cheng-Yi

first: Yan-Chu-Fei

first: Yi-Long

first: Jian-Hui

last: Chang

first: Shao-Qian

last: Wu

first: Hui-Ying

last: Wang

first: Wei-Jia

first: Zhen

last: Zhou

first: Hai-Bo

first: Quan

last: Yu

first: James

middle: W

last: Checco

first: Jonathan

last: Sweedler

first: Elizabeth

last: Cropper

first: Jian

last: Jing


title: Dual Role of NRF2 in Shaping Pancreatic Premalignant Tumors

city: New York

first: Maya

middle: Stella

last: Dixon

address: 1130 St Nicholas Ave, ICRC Floor 5 Rm 505

institute: Columbia University

summary: Pancreatic ductal adenocarcinoma (PDA) remains one of the most lethal cancers, with survival rates stubbornly low despite advances in treatment. Intraductal papillary mucinous neoplasm (IPMN) emerges as a distinct premalignant pathway, separate from the more commonly studied pancreatic intraepithelial neoplasia (PanIN). The ability to detect IPMN through imaging before malignant progression offers a transformative opportunity for early intervention in pancreatic cancer. However, the molecular determinants driving the formation of different premalignant lesions remain incompletely understood. Our study uncovers a previously unrecognized role for NRF2, a master regulator of redox homeostasis, in shaping the fate of pancreatic precursors. While NRF2 is known to promote PanIN formation and sustain PDA, we discovered a striking decrease in active NRF2 levels in human IPMN compared to PanIN and PDA. Using a conditional NRF2 knockout mouse model, we further demonstrate that NRF2 loss significantly increases the development of IPMN-like cystic tumors in KRASG12D-mutant pancreatic epithelium, revealing an unexpected role of NRF2 in suppressing IPMN. Intriguingly, while NRF2 promotes PanIN formation through redox-dependent mechanisms, its suppression of IPMN operates via a distinct pathway: the transcriptional repression of SPDEF and MUC6, both key markers of IPMN. These findings illuminate the dual and context-dependent roles of NRF2 in pancreatic tumorigenesis, providing novel insights into the molecular underpinnings of lesion-specific progression in PDA.

overall_design: We aimed to characterize the differneces between KRASG12D-PdxCre mice and KRASG12D Nrf2flox PdxCre mice

first: Shu

last: Ichimiya

first: Sung Shin

last: Ahn

first: Jack

last: O'Sullivan

first: Lela

last: Devine

first: Alex

last: Chen


title: The Unkempt RNA binding protein reveals a local translation program in centriole overduplication

city: Aurora

first: Ryan

last: Sheridan

state: CO

address: 12801 East 17th Avenue

institute: University of Colorado Anschutz Medical Campus

summary: Excess centrosomes cause defects in mitosis, cell-signaling, and cell migration, and therefore their assembly is tightly regulated. The divergent Polo kinase, PLK4, controls centriole duplication at the heart of centrosome assembly, and elevated PLK4 levels promote centrosome amplification (CA), a founding event of tumorigenesis. Here, we investigate the transcriptional consequences of elevated PLK4 and find Unkempt (UNK), a gene encoding an RNA binding protein with roles in mRNA translational regulation, to be one of only two upregulated mRNAs. UNK protein localizes to centrosomes and CEP131-positive centriolar satellites and promotes CEP131 localization to and around centrosomes. UNK's RNA binding activity is required for PLK4-induced centriole overduplication. Consistent with the loss in PLK4-induced centriole overduplication, UNK depletion disrupts PLK4 and centriole assembly protein localization. Finally, translation is enriched at centrosomes and centriolar satellites with UNK and CEP131 promoting this localized translation. In summary, UNK and CEP131 promote PLK4 localization and local translation at centrosomes during centriole overduplication.

overall_design:
Analysis of gene expression changes using RNA-seq after overexpression of PLK4 in RPE-1 cells

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The table below lists GEO accessions reused/reanalyzed for this study.
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first: Abraham

last: Martinez

first: Alexander

last: Stemm-Wolf

first: Matthew

last: Taliaferro

first: Chad

middle: G

last: Pearson


title: Genetically Engineered Mouse Models Unveil Mechanisms and Therapeutic Strategies for GMPPB-Associated Dystroglycanopathy II

city: shanghai

first: Ziwei

last: fu

address: Road Dongan 130

institute: fudan universidy

summary: Recent studies have highlighted a significant association between mutations in GDP-mannose pyrophosphorylase B (GMPPB) gene with dystroglycanopathy (DGP), a rare disease characterized by neuromuscular phenotypes. To interrogate the molecular mechanisms driving the onset and progression and to identify potential therapeutic approaches for GMPPB-associated DGP, we here constructed genetically engineered mice models of Gmppb. We show that Gmppb knockout and P32L mutant mice are lethal in the homozygous form, whereas homologous R287Q mutants are viable. Heterozygous Gmppb-P32L mutant mice exhibit reduced muscle strength, decreased locomotor ability, elevated creatine kinase levels and increased centrally nucleated myofibers. Furthermore, loss of GMPPB results in defective differentiation of muscle stem cells, leading to failure to develop into mature myotubes and diminished muscle regeneration capability. Biochemical and transcriptomic analyses indicate that loss of GMPPB is associated with significant alterations in O-linked glycosylation level, intracellular Ca2+ storage and release and the Wnt/β-catenin signaling pathway. Pharmacological activation of the Wnt pathway alleviated disruption of muscle differentiation and regeneration post muscle injury in Gmppb-deficient models. Additionally, adeno-associated virus (AAV)-mediated gene replacement therapy successfully ameliorated the muscular phenotypes. Collectively, our findings provide direct evidence that impaired muscle stem cell differentiation contributes to GMPPB-associated dystroglycanopathy. Wnt pathway agonists and AAV gene therapy represent potential effective intervention strategies for treating DGP disease.

overall_design: To investigate GMPPB's influence on muscle development, we generated GMPPB knockout C2C12 myoblast cell lines using CRISPR/Cas9.

last: Fu

first: Wei

last: Liu


title: Neurodegenerative disease-linked microRNAs acting as signaling molecules modulate CNS neuron structure and viability

city: Berlin

first: Seija

last: Lehnardt

state: Berlin

address: Charitéplatz 1

department: Institute of Cell Biology and Neurobiology, and Department of Neurology

country: Germany

institute: Charité – Universitätsmedizin Berlin

summary: The goal of this study is to compare gene expression of mouse cultured cortical neurons following exposure to extracellular miR-124-5p, and miR-92a-1-5p, which are dysregulated in Alzheimer´s disease.

overall_design:
To investigate the effect of extracellular miRNAs on neurons, we exposed mouse cortical neurons to miR-92a-1-5p, miR-124-5p and a mutated control oligonucleotide, Mut.oligo, for 6h and 5d.
Total RNA was extracted for RNA-seq, in 4 replicates, and comparative gene expression profiles were analyzed.

first: Victor

last: Kumbol

first: Andranik

last: Ivanov


title: Genetically Engineered Mouse Models Unveil Mechanisms and Therapeutic Strategies for GMPPB-Associated Dystroglycanopathy I

overall_design: To investigate the influence of GMPPB on muscle development, we created three genetically engineered mouse models: GMPPB knockout mice, GMPPB-P32L mice, and GMPPB-R287Q mice. Subsequently, we performed bioinformatics analysis on the transcriptome data obtained from muscle tissues of both GMPPB mutant mice and wild-type mice.


title: Tumor-Infiltrating CTL expansion and effector functions depends on Slc7a5-dependent tryptophan update [scRNA-seq]

city: Augusta

first: Huidong

last: Shi

state: GA

department: Georgia Cancer Center

institute: Augusta University

summary: Tumor antigen recognition and subsequent cytotoxic T lymphocyte (CTL) tumor infiltration are essential but alone are insufficient for an antitumor response. T cells nutrient uptake and metabolic reprogramming may dictate T cell differentiation and effector function to control CTL function in the tumor microenvironment. Slc7a5 is a system L transporter of large neutral amino acids and regulates T cell receptor (TCR)-mediated T cell activation during viral infection. Using tumor-specific CTL and antigen (Ag)-expressing tumor cell co-culture models, we determined that tumor-specific CTLs respond to tumor by increasing tryptophan uptake while responding to antigen alone without tumor cells by decreasing tryptophan uptake. ATAC-Seq analysis of the Ag-activated and tumor-activating CTLs revealed the transcriptional activation of a large set of transporters, including Slc7a5, a transporter for tryptophan. Slc7a5-specific inhibitor significantly decreased tryptophan uptake in the CTL-tumor co-culture while only tumor-specific CTLs and tumor are present in the microenvironment, indicating an essential role of Slc7a5 in transporting tryptophan in tumor-activated CTLs. We then generated mice with Slc7a5 deficiency only in T cells (Slc7a5.TKO). Transplanted breast tumor grew in a similar rate in WT and Slc7a5.TKO mice. However, Slc7a5.TKO mice formed significant more lung metastases than WTR mice. Further, transplanted melanoma tumor grew significantly faster in Slc7a5.TKO mice than in WT mice. Slc7a5.TKO mice show no significant difference in T cells as compared to WT mice. However, both CD4+ and CD8+ T cells diminished in tumors in the tumor-bearing mice, indicating an essential role of the Slc7a5-tryptophan metabolic pathway in T cell activation and expansion in the tumor microenvironment. scRNA-seq analysis determined that, unlike in the virus-infected host where MOTRC1 pathway is diminished, Slc7a5 deficiency leads to decreased AhR signaling and FasL expression in tumor-infiltrating T cells. Accordingly, FasL blockade increased lung metastases in breast tumor-bearing mice and increased tumor growth in melanoma tumor-bearing mice, indicating that Slc7a5 regulates the tryptophan-AhR metabolic pathway to regulate FasL expression in T cells to control tumor-infiltrating CTL effector function. Analysis of scRNA-seq dataset of human breast cancer patients revealed that FasL expression in T cells is correlated with SLC7A5 expression and patient response to immune checkpoint inhibitor immunotherapy. Furthermore, FasL is positively correlated with patient survival length in pooled datasets of 33 human cancers, and in human patients with breast cancer and melanoma in particular. Our findings determine that Slc7a5 controls tryptophan uptake in tumor-infiltrating CTLs to regulate the tryptophan-AhR metabolic pathway to regulate FasL expression to control CTL anti-tumor immune response.

overall_design: WT (Slc7a5fx/fx) and mice with Slc7a5 deletion only in T cells (Slc7a5.TKO) were injected with AT3 breast tumor cells. Tumors were dissected from the tumor-bearing mice. CD45+ cells were isolated and analyzed the 10X Genomics scRNA-seq.10xGenomics system for cDNA libraray preparation and high throughout DNA sequencing.

first: Chunwan

first: Sergei

last: Bombin

first: Kebin


title: Tumor-Infiltrating CTL expansion and effector functions depends on Slc7a5-dependent tryptophan update

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

overall_design: Refer to individual Series


title: Tumor-Infiltrating CTL expansion and effector functions depends on Slc7a5-dependent tryptophan update [RNA-seq]

overall_design: Antigen-activated and tumor-activated tumor-specific CTLs were subjected to bulk RNA-seq analysis.


title: Prenatal VEGF Nano-Delivery Reverses Congenital Diaphragmatic Hernia-Associated Pulmonary Abnormalities

city: London

first: Federica

last: Michielin

address: 30 Guilford Street

department: GOS ICH

country: United Kingdom

institute: University College London

summary: Congenital diaphragmatic hernia (CDH) affects 1-2 in 5,000 neonates who are born with hypoplastic lungs leading to significant morbidity and mortality. In severe cases tracheal occlusion (TO) can be offered to promote lung growth through airway stretch, but such growth remains limited. Vascular endothelial growth factor (VEGF), a key mediator of normal lung development, is downregulated in animal models of CDH, but its role in CDH-associated lung pathology in humans is not known. Using 18-22 post-conception week fetal lungs from CDH patients, we demonstrated for the first time that lung hypoplasia in this setting is associated with impaired VEGF expression and reduced pulmonary epithelial cell proliferation. We then developed a human ex vivo model of fetal lung compression relevant to CDH, in which a mechanical constraint was added to cultured lung fragments. Our model recapitulated impaired branching morphogenesis observed in CDH fetal lungs, and scRNAseq revealed significant reduction of the proliferative potential of terminal bud epithelial progenitors with concomitant reduction in expression of VEGF. Importantly, the exogenous supplementation of recombinant VEGF in this setting induced a significant increase of terminal bud progenitor cell proliferation, comparable to non-compressed control tissue. Finally, we developed a novel therapeutic agent delivery platform by conjugating recombinant VEGF on the surface of nanoparticles (nanodiamonds; ND-VEGF). In utero, intratracheal administration of ND-VEGF into the in vivo TO Nitrofen rat model of CDH resulted in lung growth as well as pulmonary arterial remodelling leading to histological appearances comparable to healthy controls. The beneficial effects of ND-VEGF were abrogated by co-administration of a selective VEGF-receptor-2 (KDR/Flk1) inhibitor and were not observed when unconjugated VEGF was delivered. This innovative approach could have a significant impact on the treatment of CDH.

overall_design: We combined culture of whole embryonic mouse lungs with a recently developed technology that can generate stiff barriers through selective crosslinking of Cumarin HCC-conjugated 8-arm-polyethylene glycol gel (PEG-HCC) under a two-photon microscope. Mouse lungs were freshly isolated from fetuses at 12.5 days of gestation (E12.5) and embedded in Matrigel drops placed on top of a porous cell culture insert in Air-liquid Interphase (ALI). The next day (Day 0), a 20% PEG-HCC solution was dispersed into the Matrigel drop and selectively crosslinked to surround the lungs and inhibit their growth over a total of 2 days. Control lungs had the same amount of PEG-HCC solution added to the Matrigel, but this was not crosslinked with the two-photon laser. 4 replicates were analyzed by bulk RNA-seq at Day 0, Day 2 under control conditions, Day 2 under compression conditions.

first: Stavros

middle: P

last: Loukogeorgakis

first: Noura

last: Al-Juffali

first: Julio

last: Jimenez

first: Soichi

last: Shibuya

first: Jessica

last: Allen-Hyttinen

first: Patrice

last: Eastwood

first: Ahmed

last: Alhendi

first: Joseph

last: Davidson

first: Eleonora

last: Naldi

first: Panagiotis

last: Maghsoudlou

first: Alfonso

last: Tedeschi

first: Sahira

last: Khalaf

first: Aziza

last: Khabbush

first: Manuela

last: Plate

first: Camila

last: Fachin

first: Andre

last: Dos Santos Dias

first: Nikhil

last: Sindhwani

first: Dominic

last: Scaglioni

first: Theodoros

last: Xenakis

first: Neil

last: Sebire

first: Monica

last: Giomo

first: Simon

last: Eaton

first: Jaan

last: Toelen

first: Camilla

last: Luni

first: Piero

last: Pavan

first: Peter

last: Carmeliet

first: Francesca

last: Russo

first: Samuel

last: Janes

first: Marko

middle: Z

last: Nikolic

first: Nicola

last: Elvassore

first: Jan

last: Deprest

first: Paolo

last: De Coppi


title: Tumor-Infiltrating CTL expansion and effector functions depends on Slc7a5-dependent tryptophan update [ATAC-seq]

first: Huidong

last: Shi

overall_design: Antigen-activated and tumor-activated tumor-specific CTLs were subjected to ATAC-seq analysis.

first: Chunwan

last: Liu

first: Sergei

last: Bombin

first: Kebin


title: The BET inhibitor GNE-987 effectively induces anti-cancer effects by focusing on super-enhancers in T-cell acute lymphoblastic leukemia

city: suzhou

first: yang

last: yang

address: zhongnan road

institute: soochow university


title: The BET inhibitor GNE-987 effectively induces anti-cancer effects byfocusing on  super-enhancers inT-cell acute lymphoblastic leukemia [Cut & Tag]

summary: T-cell acute lymphoblastic leukemia (T-ALL) is a highly aggressive hematologic malignant tumor that arises from T progenitor cells and accounts for 15% of childhood ALL and 25% of adult ALL cases. GNE-987 is a new chimeric molecule designed by proteolysis-targeting chimeras (PROTAC) technology. that combines an effective bromodomains and extra-targeting (BET) protein inhibitor with E3 ubiquitin ligase VHL(Von Hippel Lindau) and effectively induces proteasomal degradation of bromodomain-containing protein 4 (BRD4). GNE-987 and persistently inhibits cell proliferation and induces apoptosis, however, its anti-tumor activity GNE-987 in T-ALL has not been clarified, Here, we explore the molecular mechanisms underlying GNE-987's anti-tumor effect in T-ALL using RNA sequencing (RNA-seq) and chromatin immunoprecipitation sequencing (ChIP seq) and Cut&Tag technology.

overall_design: Genome binding/occupancy profiling of Jurkat and 6T-CEM cells treated with 10 nM for 24 h were generated by CUT&Tag.

first: Juanjuan

last: Yu

first: Jian

last: Pan


title: The BET inhibitor GNE-987 effectively induces anti-cancer effects by focusing on super-enhancers in T-cell acute lymphoblastic leukemia [RNA-Seq]

overall_design: mRNA profiles of Jurkat cells treated with 25nmol GNE987 or not for 24 h were generated by RNA sequencing, in double, using Illumina NovaSeq6000.


title: THP-1 cells infected with H37Rv

city: chongqing

first: yusheng

address: Department of Orthopedic, Southwest Hospital, Army Medical University

summary: Cells were seeded in 24-well plates with phorbol myristate (PMA, Sigma Aldrich, USA) at a concentration of 100 ng/ml. Adherent THP-1 cells were infected with H37Rv at an MOI of 1 for 4 hours, and then washed three times with PBS to remove bacteria. Experiments involving live H37Rv were performed in a P2+ facility.

overall_design: After culturing infected cells in a culture incubator for 24 hours, RNA was extracted, and uninfected cells were used as the control group

first: Yusheng

last: Yang

first: Jiezhong

last: Deng


title: Effects of chronic left ventricular pressure overload in gene expression of both atria in male rats

status: Public on May 16 2025

city: Barcelona

first: Eduard

last: Guasch

state: Catalonia

address: Rosselló 149

institute: Hospital Clinic Barcelona, IDIBAPS

summary:
Hypertension, and structural heart diseases are associated with an increased risk of atrial fibrillation. Strenuous exercise is also associated with an increased risk of atrial fibrillation. Whether similar mechanisms underly the atrial cardiomypathy in both cases is currently uknown.
We conducted an RNA microarray of right and left atria of sham and TAC rats to uncover the mechanisms driving atrial remodeling. These results were compared with remodeling induced by different loads of exercise (GSE289211).

overall_design: A group of male Wister rats were submitted to a transverse aortic constriction (TAC) or a sham surgery. Left ventricular hypertrophy of dysfunction was confirmed in all included rats in the TAC group by mean of an echocardiography. Atrial tissue was collected 6 weeks after surgery.

first: Montserrat

last: Batlle

first: Cira

last: Rubies

first: Anna

last: Alcarraz

first: Aline

last: Meza-Ramos


title: SOX9 is a driver of a stem-like transcriptional state and platinum resistance in high-grade serous ovarian cancer [Unenriched_Tumor]

city: Chicago

first: Mazhar

last: Adli

state: IL

address: 303 E. Superior St

department: Department of Obstetrics & Gynecology

institute: Northwestern University

summary: Resistance to platinum-based chemotherapies remains a formidable challenge to the treatment of high-grade serous ovarian cancer (HGSOC). The complex and multifaceted nature of this cell state has been thought to originate in a small subpopulation of inherently resistant cancer stem cells (CSCs) in naïve tumors. However, there is increasing evidence that the chemoresistance state can be transiently acquired by non-stem cancer cells as well. Regardless of the route to chemoresistance, the key regulators of this process are poorly understood. Here, we use patient-derived single-cell RNA-Seq, multimodal sequencing, tumor microarray staining, and endogenous epigenetic modulation to show that SOX9 is a key driver of chemoresistance in HGSOC. We show that genetic or epigenetic upregulation of SOX9 is sufficient to induce chemoresistance in multiple ovarian cancer cell lines. Moreover, this upregulation induces the formation of a stem-like subpopulation and can significantly decrease tumor chemosensitivity in vivo. Mechanistically, SOX9 expression drives global transcriptional divergence and reprograms the transcriptional program of naïve cells into a stem-like state. Supporting this, our multi-omic single-cell analysis identified a rare cluster of SOX9-expressing cells that are highly enriched for CSCs and chemoresistance-associated stress gene modules in a naïve tumor. Notably, single cell profiles of naïve cells show that chemo treatment results in rapid population-level expression of SOX9 that enriches for a stem-like transcriptional state. Altogether, these findings implicate SOX9 as a critical regulator of early steps of transcriptional reprogramming that leads to chemoresistance through a cancer stem-like state in HGSOC.

overall_design: Multimodal single-cell RNA and ATAC seq of a whole tissue human high grade serous ovarian tumor before patient received neo-adjuvant chemotherapy

first: Alexander

last: Duval


title: CD105+ fibroblasts support an immunosuppressive niche in women at high risk of breast cancer initiation

city: Duarte

first: Eric

middle: Gunnar

last: Carlson

address: 1500 E. Duarte Rd.

department: Population Sciences

institute: Irell & Manella Graduate School of Biological Sciences

summary: Background: Aging is the greatest risk factor for breast cancer, and although epithelial cells are the source of carcinomas, epithelial changes alone do not fully explain cancer susceptibility. Fibroblasts and macrophages are key stromal constituents around the cells of origin for cancer in breast tissue. With age, macrophages surrounding terminal ductal lobular units (TDLUs) become increasingly immunosuppressive. CD105+ fibroblasts intercalate within TDLUs, drive luminal differentiation, and give rise to immunosuppressive cancer-associated fibroblasts in other tissues. We propose that differences in fibroblasts are a crucial component of the stroma that shapes cancer susceptibility. Methods: Primary fibroblast cultures were established from prophylactic and reduction mammoplasties from women ranging in age from 16 to 70 years and breast cancer risk (BRCA1 mutation carriers). Growth characteristics, transcriptional profiles, differentiation potential, and secreted proteins were profiled for fibroblast subtypes from diverse donors. Co-cultures with fibroblasts, monocytes, macrophages, and T cells were used to ascertain the functional role played by CD105+ fibroblasts in immune cell modulation. Results: We found that peri-epithelial CD105+ fibroblasts are enriched in older women as well as women who carry BRCA1 mutations. These CD105+ fibroblasts exhibit robust adipogenesis and secrete factors related to macrophage polarization. Macrophages cocultured with fibroblasts better maintain or enhance polarization states than media alone. CD105+ fibroblasts increased expression of immunosuppressive macrophage genes. CD105+ fibroblasts supported anti-inflammatory macrophage-mediated suppression of T cell proliferation, whereas CD105− fibroblasts significantly reduced the suppressive effect of anti-inflammatory macrophages on T cell proliferation. Conclusions: Establishment of a coculture system to dissect the molecular circuits between CD105+ fibroblasts and macrophages that drive immunosuppressive macrophage polarization has broad utility in understanding mammary gland development and events that precede cancer initiation. CD105+ fibroblasts and macrophages may coordinate to suppress immunosurveillance and increase breast cancer susceptibility.

overall_design:
RNA-seq profiling of peri-epithelial fibroblasts derived from women who underwent either reduction mammoplasties or prophylactic mastectomies. Prior to sequencing, cultured fibroblasts were sorted into CD105+ and CD105- subpopulations using fluorescence-activated cell sorting.
The additional sample information (tissue source, age, BMI, ethnicity, degree of family history of cancer, treatment, hormonal replacement therapy usage, diagnosis, and BRCA1 mutational status) is provided in the 'additional_metadata.xlsx'.

first: Eric G.

first: Jennifer C.

last: Lopez

first: Yukiko

last: Yamaguchi

first: Jackson

last: Gibson

first: Saul J.

last: Priceman

first: Mark A.

last: LaBarge


title: Transcriptome Profiling of Human Dermal Fibroblasts Treated with 4 Phosphodiesterase Inhibitors Across Multiple Dose Gradients

city: SEOUL

first: Wankyu

last: Kim

institute: Ewha Womans University

summary: This study presents RNA-sequencing data from Human Primary Dermal Fibroblast, Neonatal (HDFn) cells treated with four phosphodiesterase (PDE) inhibitors—roflumilast, rolipram, cilostazol, and milrinone—across a 2-fold serial dilution range spanning from 7.8 nM to 8,000 nM. The dataset includes biological replicates for each treatment condition and dose. Total RNA was extracted and sequenced on the DNBSEQ-G400 platform. The processed data includes gene-level read counts and differential gene expression results. This dataset enables dose-dependent transcriptional profiling of PDE inhibitors, providing a resource for drug response and perturbation signature analysis.

overall_design: HDFn cells were cultured in low-serum fibroblast medium and treated with four PDE inhibitors at eleven concentrations ranging from 7.8 nM to 8,000 nM for 24 hours. Total RNA was extracted, and RNA-seq libraries were prepared using BGI’s DNBSEQ-G400 platform. Sequencing reads were processed through quality control, trimming, alignment to the human reference genome (GRCh38 v34), and quantification using HTSeq-count. Differential gene expression analysis and perturbation impact scoring were performed to characterize transcriptional changes across the dose gradient. Each treatment condition includes biological replicates to ensure reproducibility.


title: Single cell transciptional profiling of a hESC 3D extra-embryonic amnoid model (PGA - post-gastrulation amnoid)

first: Silvia

middle: DM

last: Santos

address: 1 Midland Road

institute: The Francis Crick Institute

summary: The goal of this study was to carry out a comprehensive molecular characterization of transcriptional profile and cell types formed during amniogenesis at the single-cell level. We further explored the transcriptional profiles and cell types  formed over time when the extra-embryonic cells were mixed with (primed) hESC representing cells of the inner cell mass epiblast.

overall_design: scRNA-seq was performed on cultured hESC line H1 grown in mTESR + matrigel. For induction of extraembryonic lineages, cells were treated with BMP4 (24h) and CHIR99021 (24h). For formation of co-culture samples, WT hESC grown in mTESR were mixed with  extraembryonic-induced cells. Samples were taken at 0, 1, 3, 5 and 8 days for scRNA-seq analysis. Two biological replicates per condition were multiplexed using Cell Multiplexing Oligos (CMO) (10x Genomics 3′ Cellplex kit set A (PN-1000261)) and sequenced together.


title: Deciphering HAND Pathogenesis Using Single-Nucleotide Omics Approaches

city: Washington

first: Anelia

last: Horvath

state: DC

address: 2300 I St NW

department: Biochemistry and Molecular Medicine

institute: George Washington University

summary: Although antiretroviral therapy (ART) effectively suppresses HIV-1 replication to undetectable levels and restores many immune parameters in people living with HIV (PLWH), these individuals remain at elevated risk for HIV-associated comorbidities. Among the most prevalent is neurocognitive impairment—a mild form of HIV-associated neurocognitive disorders (HAND)—which affects up to 50% of PLWH. Despite extensive investigation, the precise mechanisms underlying HAND pathogenesis remain unclear, in part due to its multifactorial nature. To address this, we conducted a comparative single-nucleus multi-omics analysis—integrating RNA sequencing (RNA-seq) and chromatin accessibility profiling (ATAC-seq)—of post-mortem brain tissues from HIV-infected individuals with and without HAND, as well as uninfected controls. Our results reveal substantial dysregulation in genes involved in inflammation, innate immunity, glycosylation, and cholesterol metabolism in HIV-infected brains (HAND+ and HAND−) relative to uninfected controls. Notably, these changes were further accentuated in HAND+ samples compared to HAND−, with microglia and oligodendrocytes emerging as the most affected cell populations—highlighting their potential central role in sustaining neuroinflammation. Interestingly, we observed a disconnect between transcriptomic and epigenomic signals: many inflammation-related genes located in accessible chromatin regions in HAND+ brains were not transcriptionally upregulated. This epigenetic priming—particularly in microglia and astrocytes—is consistent with the concept of trained immunity (TRIM), wherein prior exposures epigenetically “train” innate immune cells to respond differently to subsequent stimuli. Our findings suggest that maladaptive TRIM may be a key contributor to persistent neuroinflammation and the pathogenesis of HAND in the ART era.

overall_design: paired single-nuclei multiomic RNA and ATAC sequencing profiling of HAND and Non-HAND flash frozen brain tissue samples

first: Michael

last: Bukrinsky

first: Dmitri

last: Sviridov

first: Tatiana

last: Pushkarsky

first: Siera

last: Martinez


title: SOX9 is a driver of a stem-like transcriptional state and platinum resistance in high-grade serous ovarian cancer

overall_design: Multimodal single-cell RNA and ATAC seq of a epithelial-cell-enriched human high grade serous ovarian tumor before patient received neo-adjuvant chemotherapy

middle: J


title: TIA1-mediated stress granules promote the neurodegeneration of motor neurons through sequestrating mRNA of heat shock protein HSP70 family in C9orf72-poly-GA mice

city: Hang Zhou

first: Yan

last: Wei

state: Zhejiang

address: 2318 Yuhang Tang Road

department: Medicine

institute: Hangzhou Normal University

summary: TIA1 knockout in the central nervous system (TIA1Nestin-CKO mice) alleviated motor neuron loss, neuroinflammation and motor dysfunction in C9orf72-poly-GA mice. Mechanistically,  we performed RNA-sequencing to find the differentially expressed genes between ALS-WT and ALS-CKO mice.

overall_design: Compareative gene expression profiling analysis of RNA-seq data for ALS-WT and ALS-CKO mice motor cortex.

first: Dongmei

last: LI

first: Rui

last: Yang

first: Yanzhu

last: Liu

first: Xuan

last: Luo

first: Weiqiao

last: Zhao

first: Hui