title: A Single-cell Atlas of Schwannoma Across Genetic Backgrounds and Anatomic Locations

city: Boston

first: L. Nicolas

last: Gonzalez Castro

state: MA

address: 60 Fenwood Road

institute: Mass General Brigham

summary: Background: Schwannomas are nerve sheath tumors arising at cranial and peripheral nerves, either sporadically or in patients with a schwannomatosis-predisposition syndrome. There is limited understanding of the transcriptional heterogeneity of schwannomas across genetic backgrounds and anatomic locations. Methods: Here, we prospectively profile by single-cell full-length transcriptomics tumors from 22 patients with NF2-related schwannomatosis, non-NF2-related schwannomatosis, and sporadic schwannomas, resected from cranial and peripheral nerves. We profiled 11,373 cells, including neoplastic cells, fibroblasts, T cells, endothelial cells, myeloid cells and pericytes. Results: We characterize the intra-tumoral genetic and transcriptional heterogeneity of schwannoma, identifying six distinct transcriptional metaprograms, with gene signatures related to stress, myelin production, antigen presentation, interferon signaling, glycolysis and extracellular matrix. We demonstrate the robustness of our findings with analysis of an independent cohort. Conclusion: Overall, our atlas describes the spectrum of gene expression across schwannoma entities at the single-cell level and will serve as important resource for the community.

overall_design: Adult patients with radiographic evidence of schwannoma provided preoperative informed consent to take part in the study in all cases after the Institutional Review Board Protocols DF/HCC 10- 417 and DF/HCC 15-370B. Among these patients were patients that had received a diagnosis of NF2-related schwannomatosis or non-NF2-related schwannomatosis based on current clinical diagnostic criteria. Patients were males and females. Sample processing and single-cell RNA-seq data generation: Fresh tumors were collected directly from the operating room at the time of surgery and presence of schwannoma was confirmed by frozen section. Tumors were mechanically and enzymatically dissociated using a papain-based tumor dissociation kit (Miltenyi Biotec). Tumor cells were blocked in 1% bovine serum albumin in Hanks buffered saline solution (BSA / HBSS). Tumors were first stained first with CD45- Vioblue direct antibody conjugate (clone REA747, Miltenyi Biotec) for 30 min at 4deg C. Cells were washed with cold PBS, and then re- suspended in 1mL of BSA / HBSS containing 1 mM calcein AM (Life Technologies) and 0.33 mM TO-PRO-3 iodide (Life Technologies) to co-stain for 30 min before sorting. CD45 negative cells were stained with calcein AM (Life Technologies) for viability and CD24-APC (human antibody, clone REA832, Miltenyi Biotec) and CD44-VioBlue (human antibody, clone REA690, Miltenyi Biotec) to sort subpopulations of viable non-immune cells. Sorting was performed with the FACS Aria Fusion Special Order System (Becton Dickinson) using 488 nm (calcein AM, 530/30 filter), 640nm (TO-PRO-3 or CD24-APC, 670/14 filter), and 405 nm (CD45-VioBlue or CD44-VioBlue, 450/50 filter) lasers. Standard, strict forward scatter height versus area criteria were used to discriminate doublets and gate only singleton cells. Viable single cells were identified as calcein AM positive and TO-PRO-3 negative. We sorted individual, viable, immune, and non-immune single cells into 96- well plates containing TCL buffer (QIAGEN) with 1% beta-mercaptoethanol. Plates were frozen on dry ice immediately after sorting and stored at -80deg C prior to whole transcriptome amplification, library preparation and sequencing. Smart-seq2 whole transcriptome amplification, library construction, and sequencing were performed.

first: Avishai

last: Gavish

first: Itay

last: Tirosh

first: Mario

last: Suva


title: Nidogen-1, a player in KMT2A rearragned pediatric acute myeloid leukemia

status: Public on Apr 17 2025

city: Ghent

first: Jolien

last: Vanhooren

address: Corneel Heymanslaan 10

country: Belgium

institute: Ghent University

type: Expression profiling by high throughput sequencing

summary: Despite advances in outcome, one third of children with acute myeloid leukemia (AML) relapse, and less than half will achieve long-term survival. Relapse in AML has shown to be driven in part by the leukemic stem cells (LSC), highlighting the unmet medical need to better characterize and target this therapy resistant cell population. Micro-array profiling of pediatric AML subpopulations (LSC and leukemic myelo-blasts) and their healthy counterparts, revealed Nidogen-1 (NID1) as expressed in both leukemic subpopulations, while absent in the hematopoietic stem cell. Using the TAR-GET dataset including pediatric AML patients (n=1025), NID1 expression showed to correlate with worse event-free survival and KMT2A-rearrangements. Drug response profiling of a NID1 knockdown model demonstrated differential sensitivity to HSP90 inhibition. RNA sequencing and gene set enrichment analysis between NID1high and NID1low phenotypes showed involvement of NID1 in mitochondrial metabolic path-ways known to be enriched in the LSC. Altogether, this study highlights NID1 as a novel oncogene associated with worse EFS and metabolic LSC phenotype in AML. NID1 could serve as a biomarker and aid in further mapping LSCs to establish thera-peutic strategies tackling the high relapse rates in pediatric AML.

overall_design: As higher NID1 expression was shown to be associated with worse event-free survival, we aim to uncover more about the biological role of NID1 in pedAML. Therefore, we generated cell line models with altered NID1 gene expression by means of lentiviral shRNA knockdown in THP-1 and NID1 overexpression in the KASUMI-1 cell line.

first: Tim

last: Lammens

first: Barbara

last: De Moerloose


title: African swine fever infection epigenetically regulate host membrane protein-encoding genes

status: Public on Apr 18 2025

city: wuhan

first: zhe

last: jin

state: hubei

address: Lion Rock Street

department: College of Animal Science and Technology

country: China

institute: Huazhong Agricultural University

type: Genome binding/occupancy profiling by high throughput sequencing

summary: African swine fever virus (ASFV) is a highly contagious pathogen that primarily affects domestic and wild pigs with specific tropism to porcine alveolar macrophages (PAMs). However, the host receptors involved in ASFV infection remain unknow. Here, we present a multi-omic epigenetic atlas of ASFV-exposed PAMs and profile 3D chromatin architecture and single-nucleus chromatin accessibility landscapes (sn-ATAC)

overall_design: AMs with ASFV and assessed gene expression (RNA-seq),Genomic DNA samples from ASFV infected PAMs and uninfected controls were then analyzed for multiple chromatin modification states by CUT&Tag (H3K4me3, H3K27ac, H3K27me3 and Pol2),sn-ATAC to map the transposase-accessible chromatin at the single-cell level,Through a high-resolution chromatin conformation capture technique(BL-HiChIP)

first: Liangliang

last: Fu

first: Xiaolong

last: Qi

first: Yue

last: Xiang

first: Limeng

last: Sun

first: Jingjin

last: Li

first: Lu

last: zhang

first: Peng

last: Zhou

first: Zhuqing

last: Zheng

first: Qiulin

last: Zhao

first: Lingyu

last: Xing

first: SaiXian

last: Zhang


title: Oncogenic transcription factor targets

city: Turku

first: Otto

last: Kauko

address: Tykistökatu 6

department: Turku Bioscience Centre

country: Finland

institute: University of Turku

summary:
Transcription factors ERG and AR (prostate cancer), ER (breast cancer), CTNNB1 (colorectal cancer), GLI1 and PAX3-FOXO1 fusion (Rhabodomyosarcoma) have been shown to be critical for the formation of tumors. The purpose of this study was to identify common targets of these transcription factors.
We used microarrays to study gene expression in response to modulating these transcription factors by RNAi (ERG, CTNNB1, GLI1, PAX3-FOXO1) or their ligands (AR and ER).

overall_design: Cancer cell lines were treated with with two siRNAs in duplicates to knock down the targeted TFs or, in the case of hormone receptor TFs AR and ER, stimulated with their natural ligands to induce the activity of these TFs. RNA was extracted and hybridized on Affymetrix microarrays.

first: Mikko

last: Turunen

first: Gong-Hong

last: Wei


title: DIFFERENTIAL TEMPERATURE-INDUCED RESPONSES IN ORAL AND SKIN KERATINOCYTES

city: Chicago

first: Chen

last: Han

state: IL

address: 801 S. Paulina St.

department: Center for Wound healing and Tissue Regeneration

country: USA

institute: University of Illinois Chicago

summary: The epidermis of skin and oral mucosa is constantly exposed to various environmental stimuli, including temperature changes. In particularly extreme conditions, such as excess heat or cold, significant injury may occur. Oral and skin keratinocytes exhibit tissue-specific differences in wound healing outcomes and the transcriptomic response to injury. This study investigated if skin and oral keratinocytes also have differential responses to heat and cold-induced injury. Oral keratinocytes (TIGK) were found to exhibit an enhanced viability following heat-induced injury compared to skin keratinocytes (HaCaT). However, there were no discernible differences between skin and oral keratinocyte viability following cold-induced injury. To examine the transcriptomic differences between skin and oral keratinocytes in response to temperature-induced injury, we generated an mRNA-sequencing gene expression dataset. Differentially expressed genes (DEGs) including heat shock proteins (HSPs) were identified between HaCaT and TIGK at baseline (37°C) and after heat (60°C) or cold-induced (-25°C) injury. Our comparative analyses suggest that skin and oral keratinocytes exhibit transcriptomic differences at baseline and in their responses to heat or cold exposure. The enhanced heat tolerance of TIGK relative to HaCaT may be due to an advantageous expression of a subset of HSPs at baseline in TIGK. Our work also provides a source of skin and oral keratinocyte gene expression data following heat and cold-induced injury that can be used for future analyses.

overall_design: RNA-sequencing (RNA-seq) profiling of skin and oral keratinocyte cell lines, HaCaT and TIGK, at 3 distinct temperatures: -25°C, 37°C, and 60°C


title: Diverse Cell Types Establish a Pathogenic Immune Environment in Peripheral Neuropathy

city: St. Louis

first: Julie

last: Choi

state: MO

address: 4370 Duncan Avenue

department: Genetics

institute: Washington University in St. Louis

summary: Neuroinflammation plays a complex and context-dependent role in many neurodegenerative diseases. We identified a key pathogenic function of macrophages in a mouse model of a rare human congenital neuropathy in which SARM1, the central executioner of axon degeneration, is activated by hypomorphic mutations in the axon survival factor NMNAT2. Macrophage depletion blocked and reversed neuropathic phenotypes in this sarmopathy model, revealing SARM1-dependent neuroimmune mechanisms as key drivers of disease pathogenesis. In this study, we investigated the impact of chronic subacute SARM1 activation on the peripheral nerve milieu using single cell/nucleus RNA-sequencing (sc/snRNA-seq). Our analyses reveal an expansion of immune cells (macrophages and T lymphocytes) and repair Schwann cells, as well as significant transcriptional alterations to a wide range of nerve-resident cell types. Notably, endoneurial fibroblasts show increased expression of chemokines (Ccl9, Cxcl5) and complement components (C3, C4b, C6) in response to chronic SARM1 activation, indicating enhanced immune cell recruitment and immune response regulation by non-immune nerve-resident cells. Analysis of CD45+ immune cells in sciatic nerves revealed an expansion of an Il1b+ macrophage subpopulation with increased expression of markers associated with phagocytosis and T cell activation/proliferation. We also found a significant increase in T cells in sarmopathic nerves. Remarkably, T cell depletion rescued motor phenotypes in the sarmopathy model. These findings delineate the significant changes chronic SARM1 activation induces in peripheral nerves and highlights the potential of immunomodulatory therapies for SARM1-dependent peripheral neurodegenerative disease.

overall_design:
'- Single-cell RNA sequencing of WT and Nmnat2 V98M/R232Q mouse sciatic nerves at 2-3-month
- Single-nucleus RNA sequencing of WT and Nmnat2 V98M/R232Q mouse sciatic nerves at 2-3-month
- FACS sorted CD45+ single-cell RNA sequencing of WT and Nmnat2 V98M/R232Q mouse sciatic nerves at 2-3-month

first: Amy

last: Strickland

first: Wendy

last: Dong

first: Jeffrey

last: Milbrandt


title: The neural crest-associated gene FOXD1 induces an immunosuppressive microenvironment by regulating myeloid-derived suppressor cells in melanoma

city: Heidelberg

first: Jochen

last: Utikal

address: Im Neuenheimer Feld 280

department: Clinical Cooperation Unit Dermato-Oncology

country: Germany

institute: German Cancer Research Center

summary: Background Neural crest (NC)-associated genes play pivotal roles in tumor initiation, progression, and the intricate dynamics of the tumor microenvironment (TME). Myeloid-derived suppressor cells (MDSC) within the TME are important in dampening T cell activity and contributing to resistance against immunotherapeutic interventions. The NC-associated gene Forkhead Box D1 (FOXD1) has been identified as an oncogenic factor that induces melanoma dedifferentiation and progression. However, the underlying mechanisms and the impact of FOXD1 on the antitumor immune response remain unclear.   Methods To investigate the impacts of FOXD1 on the melanoma microenvironment, we analyzed publicly available datasets from multiple platforms, including TNMplot, Timer 2.0, etc. In addition, FOXD1 was overexpressed or knocked down in melanoma cells to identify its biological functions in vitro and in vivo. Flow cytometry and arginase activity assay were used to analyze the phenotype and function of MDSC. Western blot, RT-PCR, or ELISA assays were employed to analyze the expression of FOXD1 and its regulated factors. In vivo experiments were conducted to investigate the role of FOXD1 in melanoma progression and the influence on MDSC accumulation within the tumor microenvironment.  Results We demonstrate that increased FOXD1 levels inversely correlated with melanoma responsiveness to immunotherapy. Ex-vivo analyses unveiled that monocytes, exposed to condition medium from FOXD1-overexpressing (OE) melanoma cells, effectively suppressed T cell proliferation and upregulated the expression of PD-L1 and other immunosuppressive factors. FOXD1 was identified as a direct regulator of IL6 expression, which is pivotal for MDSC induction. Blocking IL6 reversed MDSC-associated immunosuppression. Additionally, miR-581, a potential negative regulator of FOXD1, attenuated the impact of FOXD1 on IL6 expression and MDSC differentiation. In vivo experiments demonstrated tumors derived from FOXD1 OE melanoma cells contained a significantly higher percentage of PD-L1⁺ MDSC compared to controls, while FOXD1 knockdown (KD) resulted in reduced tumor growth and diminished MDSC accumulation.

sample_organism:
Homo sapiens
Mus musculus

platform_organism:
Homo sapiens
Mus musculus

overall_design: total RNA isolated from FOXD1 silenced cells and its control cells, FOXD1 overepressed cells and its control cells ，miRNA-581 mimics treated cells and its control (miRNA-NC mimics) cells

first: Qian


title: Targeting Innate Immune Signaling in Glioma-Initiating Cells Impairs Self-Renewal and Radiation-Induced Cellular Plasticity

city: Los Angeles

first: Frank

last: Pajonk

state: CA

address: 10833 Le Conte Ave

institute: UC Los Angeles

summary: Purpose: Organisms constantly face environmental stressors that threaten their cellular and genomic integrity. In their response, pathogen-associated molecular patterns (PAMPs) and/or damage-associated molecular patterns (DAMPs) are detected by pattern recognition receptors (PRRs) and trigger the innate immune response. In this study we tested the hypothesis that DAMPs contribute to radiation-induced cellular plasticity in Glioblastoma (GBM). GBM is known to be organized hierarchically with a small number of glioma-initiating cells (GICs) driving treatment resistance and recurrences. Materials and Methods: Using patient-derived GBM specimens, we employed sphere forming capacity assays and in vitro extreme limiting dilution assays to examine how innate immune receptor signaling impacts the maintenance and self-renewal of GICs. By leveraging an imaging system for putative GICs we determined de novo induction of GICs from non-stem glioma cells. Results: We find that GIC maintenance after irradiation is mediated by cGAS-independent STING signaling, possibly involving signaling through TLR4 and TLR9. Induction of radiation-induced plasticity involves TLR3 signaling, with potential roles for other receptors and processes modulated by MyD88. Conclusion: These findings suggest that targeting innate immune signaling could prevent radiation-induced cellular plasticity for potential therapeutic benefit.

overall_design: HK-374 cells were seeded into 6-well plates as monolayer cultures at 40,000 cells/well. 4 days after seeding the cells were irradiated with 4 Gy in the presense or absence of H151. Controls were sham irradiated. RNA was harvested 48 h after irradiation.


title: Long term exposure of PP-MP has no effect on the metabolism of mice.

city: seoul

first: sungguan

last: hong

address: 84, Heukseok-ro, Dongjak-gu, Seoul, 104-407

department: Chemistry

country: South Korea

institute: Chung-Ang

summary: Microplastics are defined as plastics ranging in size from 0.1μm to 5mm. Currently, research is being conducted across various fields to examine the effects of microplastics. Some studies demonstrated negative impacts on cells and mice. However, there is a lack of research on the effects by long-term exposure to microplastics. Most of the papers evaluated cytotoxicity with period of less than 2 months. Therefore, in this study, we investigated the potential issues that may arise from prolonged exposure through food mixed with Polypropylene microplastic (PP-MP) for over a year. We divided our study into short, mid, and long-term periods to assess cytotoxicity through Glucose tolerance test, Insulin tolerance test, analysis of insulin and c-peptide levels, hanging, grip, treadmill, Y-maze and open field tests, Respiratory Exchange Ratio, Energy Expenditure, Activity, and body composition. Through this, we comprehensively examined potential issues related to mouse behavior, muscle, metabolism and other factors. After dissection, RNA sequencing was carried out to investigate the effects on genes. For further verification, RT-qPCR was conducted. To summarize, our study provides evidence suggesting that treatment of microplastics for a short term has adverse effects, but with prolonged exposure, their effects tend to diminish.

overall_design: To assess the impact of prolonged Polypropylene Microplastic (PP-MP) exposure on mice, hepatic gene expression profiles were analyzed.

first: Bokyung

last: Kim

first: Gyeong Bae

last: Song

first: Jeein

last: Hong

first: Gijeong

last: Woo

first: Mi Jung

first: Sungguan


title: RNA-Seq analysis of the knockout and endosperm-specific expression of OsADCS and OsGTPCH1 in rice.

city: Hangzhou

first: Fengli

last: Zhao

state: Zhejiang

address: No. 28 of Shuidaosuo Road

department: State Key Laboratory of Rice Biology and Breeding

institute: China National Rice Research Institute

summary: The functions of OsADCS and OsGTPCH1 need to be understood. We further compared and analyzed the transcriptional levels between single-knockout, co-knockout, single-expression, and co-expression with the wild-type, clarified the regulatory mechanisms of OsADCS and OsGTPCH1 during seed development.

overall_design: Selecting seeds 25 days after flowering from 6 transgenic lines and wild-type, RNA-Seq was used to investigate the effects of OsADCS and OsGTPCH1 on whole gene expression and general metabolism.


title: Effect of PM2.5 on circRNA expression of HBE cells

city: Beijing

first: Rui

last: Chen

address: No.10 Xitoutiao, You An Men

institute: Capital medical university

type: Non-coding RNA profiling by high throughput sequencing

summary: To further explore the potential mechanism underlying PM2.5-induced lung tumorigenesis, we performed circRNA sequencing (circRNA-seq) using RNA isolated from control  or chronic PM2.5 exposed HBE cells (control n=3 vs. PM2.5 n=3)

overall_design: circRNA-seq of HBE cells with or without chronic PM2.5 treatment

first: Shen

middle: s

last: Wu


title: Effect of circDNA2 on gene expression of chronic PM2.5 exposed HBE cells

summary: To identify the direct targets of circDNA2 in chronic PM2.5 exposed HBE cells, we performed RNA sequencing (RNA-seq) using RNA isolated from chronic PM2.5 exposed HBE cells or circDNA2 knockdown chronic PM2.5 exposed HBE cells (NC n=3 vs. KD n=3)

overall_design: RNA-seq of chronic PM2.5 exposed HBE cells with or without circDNA knockdown


title: MiR-574-3p and miR-125a-5p in adipose derived mesenchymal stem cell exosomes synergistically target TGF-β1SMAD2 signaling pathway for the treatment of androgenic alopecia

city: Tongliao

first: Cong

last: Ma

address: 1742 East Section of Huolinhe Street

department: Dermatology

institute: The Affiliated Hospital of Inner Mongolia University for the Nationalities

summary: Androgenetic alopecia (AGA) is the most common hair loss disorder, influenced by distinct genetic factors and intricate environmental factors. The exosomes (Exo) from adipose-derived mesenchymal stem cells (ADMSCs) have diverse effects, including the promotion of cell proliferation, inhibition of apoptosis, analgesia, and enhancement of wound healing. The miRNAs are essential components of the paracrine secretion of ADMSCs-Exo. This study revealed that ADMSCs-Exo could counteract the impairment of dermal papilla cells (DPCs) induced by dihydrotestosterone (DHT) by inhibiting the TGF-β1 signaling pathway`s activation.However, the exosomes derived from ADMSCs adipogenic differentiation (ADMSCsAd-Exo) lacked this therapeutic potential. Expression profiling of miRNAs in ADMSCs-Exo and ADMSCsAd-Exo by genomic microarray analysis. MiR-574-3p and miR-125a-5p, were identified as being predominantly expressed and specifically targeting TGF-β1 and SMAD2, respectively. Ultimately, our findings indicate that ADMSCs-Exo target the TGF-β1/SMAD2 signaling pathway via miR-574-3p and miR-125a-5p, are integral to their therapeutic action on DHT-induced DPCs and AGA murine models. This discovery offers significant insights into the pathogenesis of AGA and suggests potential therapeutic approaches. Further investigation into the role and interaction of these miRNAs in ADMSCs-Exo may lead to the development of more precise and efficacious treatments for AGA.

overall_design: Compare miRNAs in ADMSCs-Exo and ADMSCsAd-Exo (adipogenic differentiation 14d), with 3 samples per group.

first: Xuegang

last: Xu


title: KRT14 knockdown enhances cisplatin-resistance through upregulating LRP11 expression in ovarian cancer

city: Guangzhou

first: Zequn

last: Liu

state: Guangdong

address: 9 Jinsui Road, Tianhe District

department: Department of Obstetrics

institute: Guangzhou Women and Children’s Medical Center, Guangzhou Medical University

summary: Ovarian cancer is a highly malignant gynecological tumor. Multidrug resistance (MDR) in tumors is a major reason for chemotherapy failure. Keratin 14 (KRT14), a member of the keratin family, plays a significant role across various cancers. Elevated KRT14 expression has been observed in ovarian cancer tissues compared to normal ovarian tissues, and this differential expression is associated with poorer progression-free survival in patients undergoing platinum and taxol-based chemotherapy. Furthermore, KRT14 expression is heightened in migratory ovarian cancer cells, where it plays a crucial role at the invasive interface, facilitating ovarian cancer cell invasion. The role of KRT14 in regulating MDR is not known. In this study, we aimed to investigate the effects and mechanisms of KRT14 in human cisplatin-resistant ovarian cancer cell lines SK-OV-3/DDP and A2780/DDP.

overall_design: SK-OV-3/DDP and A2780/DDP cells were transfected with small interfering RNA (siRNA) targeting KRT14 (siKRT14) or negative control siRNA (siNC) for 24 h and then cells were harvested for RNA sequencing.

first: Ting-song

last: Weng

first: Mi

last: Cheng

first: Ting-ying

last: Lei

first: Du

last: Xiao

first: Qiong

last: Deng

first: Tianmei


title: Unique N-glycosylation signatures in human iPSC derived microglia activated by Aβ oligomer and lipopolysaccharide

city: Sacramento

first: Izumi

last: Maezawa

institute: University of California Davis Medical Center

summary: Microglia are the immune cells in the central nervous system (CNS) and become pro-inflammatory/activated in Alzheimer’s disease (AD). Cell surface glycosylation plays an important role in immune cells, however, the N-glycosylation and glycosphingolipid (GSL) signatures of activated microglia are poorly understood. Here, we study comprehensive combined transcriptomic and glycomic profiles using human induced pluripotent stem cells-derived microglia (hiMG). Distinct changes in N-glycosylation patterns in Aβ oligomer (AβO) and LPS -treated hiMG were observed. In AβO treated cells, the relative abundance of bisecting N-acetylglucosamine (GlcNAc) N-glycans decreased, corresponding with a downregulation of MGAT3, the gene responsible for bisecting GlcNAc N-glycan formation. The sialylation of N-glycans increased in response to AβO, accompanied by an upregulation of genes involved in N-glycan sialylation (ST3GAL2, 4, and 6). Moreover, we found that the N-glycosylation signature of LPS-induced hiMG differed from that of AβO-induced hiMG. LPS-induced hiMG exhibited a decreased abundance of complex-type N-glycans, aligned with downregulation of mannosidase genes (MAN1A1, MAN2A2, MAN1C1). Fucosylation increased in LPS-induced hiMG, aligned with upregulated fucosyltransferase 4 (FUT4) and downregulated alpha-L-fucosidase 1 (FUCA1) gene expression. However, the GSL profile did not exhibit significant changes in response to AβO or LPS activation. AβO- and LPS- specific glycosylation changes could contribute to impaired microglia function, highlighting glycosylation pathways as potential therapeutic targets for AD.

overall_design: Human iPS Cell Line 26 (Episomal, CD34+, ApoE3) were cultured and differentiated into microglia (hiMG). Two experimental sets of hiMG samples were sequenced: one with control and LPS-treated hiMG, and another with control and Aβ oligomer (AβO)-treated hiMG. For both experiments, six biological replicates were used in each group.

first: Xinyu

last: Tang

first: Jacopo

last: Di Lucente

first: Lee-Way

last: Jin


title: Harnessing Apple Cell Suspension Cultures in Bioreactors for Triterpene Production: Transcriptomic Insights into Biomass and Triterpene Biosynthesis

city: Belvaux

first: Sylvain

last: Legay

address: 41, rue du Brill

department: ERIN department

country: Luxembourg

institute: Luxembourg Institute of Science and Technology

summary: Plant cell suspension cultures offer a sustainable method for producing valuable secondary metabolites, such as bioactive pentacyclic triterpenes. This study established a high-triterpene-yielding cell suspension culture from the apple cultivar "Cox Orange Pippin." Through transcriptomic analysis and triterpene profiling across growth phases, we uncovered complex regulatory networks that govern biomass production and triterpene biosynthesis. Key biological processes, including cell cycle regulation, cell wall biosynthesis, lipid metabolism, and stress response mechanisms, play pivotal roles in culture dynamics. Differential gene expression linked to these processes revealed how the culture adapts to growth conditions and nutrient availability at each growth phase. Methyl jasmonate elicitation enhanced phenylpropanoid and flavonoid biosynthesis, along with specific triterpene production pathways, highlighting its potential for optimizing secondary metabolite production. Key enzymes, including oxidosqualene cyclase 4 and a putative C-2α hydroxylase, emerged as promising targets for future metabolic engineering of triterpene pathways. This study represents the first in-depth report on the molecular mechanisms underlying plant cell growth in bioreactors, specially focusing on a non-model plant species . These findings reveal key regulatory pathways in biomass accumulation and triterpene production, offering insights to optimize bioreactor cultures for industrial use. The research opens new avenues to enhance triterpene yields via targeted metabolic engineering and innovative bioprocessing strategies, paving the way for efficient large-scale production.

overall_design: A Malus x domestica cell line produced from the Cox orange Pippin variety was grown in bioreactors with three biological replicates. Cells were sampled during the course of the batch to investigate gene expression patterns being involved in the different growth stages (lag phase, exponential phase, stationnary phase, post elicitation)

first: Xuan

last: XU

first: Emmanuelle

last: COCCO

first: Gea

last: GUERRIERO

first: Kjell

last: SERGEANT

first: Samuel

last: JOURDAN

first: Jenny

last: RENAUT

first: Jean-Francois

last: HAUSMAN

last: LEGAY


title: Single-cell transcriptome sequencing reveals the cellular heterogeneity of small intestine tissue in celiac disease

city: Urumqi

first: Tian

last: Shi

address: No. 91, Tianchi Road, Tianshan District, Urumqi, Xinjiang, China

institute: Department of Gastroenterology, People’s Hospital of Xinjiang Uygur Autonomous Region

summary: Background: Celiac disease (CeD) is an autoimmune small intestinal disease caused by gluten protein ingestion by genetically susceptible individuals. Genome-wide association studies and transcriptomic data have limited capacity to capture intercellular genetic variations. We aim to construct a single-cell transcriptome spectrum, analyze the immune microenvironment and cellular heterogeneity, discover disease-related specific genes and markers, and explore the pathogenesis of CeD. Methods: We performed single-cell RNA sequencing (scRNA-seq) on three small intestine biopsies from patients with CeD and three healthy Chinese controls. Immunohistochemistry (IHC) and quantitative PCR (qPCR) were used to validate potential diagnostic biomarkers of disease-differential genes. Results: A total of 10 cell subpopulations were annotated, including three types of epithelial and stromal cells and seven types of immune cells. IHC revealed a pronounced overexpression of T cell disease-differential genes, TRAT1, BCL11B, and ETS1 in intraepithelial lymphocytes in the CeD group. Further clinical validation using qPCR confirmed that ETS1 (P = 0.010), TRAT1 (P ＜ 0.001), and BCL11B (P = 0.036) w

overall_design: Three healthy control individuals (Ctrl group) were recruited from the Health Examination Center of the People’s Hospital of Xinjiang Uyghur Autonomous Region. These individuals were carefully selected to match the three patients with CeD in terms of age, sex, and ethnicity, thereby ensuring a controlled comparison. Controls were screened using serum-specific antibodises (anti-tissue transglutaminase antibody and anti-endomysial antibody) to exclude any CeD cases. The exclusion criteria included a history of malignant tumors, other autoimmune diseases, acute cardiovascular or cerebrovascular disease (within the last six months), history of gastrointestinal surgery, contraindications to endoscopic biopsy, and refusal to participate in the study. We performed single-cell RNA sequencing (scRNA-seq) on three small intestine biopsies from patients with CeD and three healthy Chinese controls. Immunohistochemistry (IHC) and quantitative PCR (qPCR) were used to validate potential diagnostic biomarkers of disease-differential genes.

first: Shi

last: Tian


title: Effect of hypoxia on gene expression in Hep3B cells

city: Xi'an

first: Yufeng

last: Wang

address: 277 West Yanta Road, Xi'an, Shaanxi, P.R.China

institute: the first affiliated hospital of Xi'an Jiaotong university

summary: Hypoxic microenvironment plays a critical role in solid tumor progression. More and more protein coding and non-coding RNA genes have been identified as hypoxia-regulated genes in HCC. Thus, we attempted to identify more novel hypoxia-regulated genes in HCC with Hep3B cells exposed to 20% or 1% oxygen.

overall_design: Hep3B cells were exposed to 20% or 1% oxygen for 24 hours, then the total RNA was isolated for subsequent test.


title: Human mRNA profile of Mycobacterium tuberculosis H37Rv infected and hsa-miR-643 mimic transfected THP-1 differentiated macrophages cells.

city: LUCKNOW

first: Bhupendra

middle: N

last: Singh

state: Please select

address: Janakipuram Sector 10

department: Molecular Microbiology & Immunology

country: India

institute: CSIR-CDRI

summary: The analysis of differentially regulated mRNAs candidates in THP-1 cells infected with H37Rv was conducted, comparing them to both uninfected THP-1 cells and transfected reference samples. THP-1 cells are monocytes that differentiate into macrophages after being treated with PMA for 48 hours. Total RNA was isolated from the infected and transfected THP-1 cells at 24 hours post-infection.

overall_design: Expression profiling by RNA sequencing.

first: Garima

last: Kumari

first: Mohd

middle: M

last: Ansari


title: Precision RNA Base Editing in Plant Organelles Using Engineered Synthetic P-type PPR Editing Factors

city: Strasbourg

first: Kamel

last: HAMMANI

address: 12 rue du general Zimmer

country: France

institute: CNRS

summary: RNA editing, particularly cytidine-to-uridine conversions in plant organelles, plays a crucial role in regulating gene expression. While natural PLS-type PPR proteins are specialized in this process, synthetic PPR proteins offer significant potential for targeted RNA editing. In this study, we engineered chimeric editing factors by fusing synthetic P-type PPR guides with the DYW cytidine deaminase domain from a moss mitochondrial editing factor, PPR56. These designer PPR editors (dPPRe) were tested in Escherichia coli and Nicotiana benthamiana chloroplasts and mitochondria, demonstrating efficient and precise de novo RNA editing. Transcriptome-wide analysis of the most efficient chloroplastic dPPRe revealed minimal off-target effects, with only three non-target C sites edited due to sequence similarity with the intended target. This study introduces a novel and precise method for RNA base editing in plant organelles, paving the way for new approaches in gene regulation applicable to plants and potentially other organisms.

overall_design:
To investigate the effect of dPPRerpl2 on chloroplast gene expression and RNA editing, we transiently expressed this construct with the P19 silencing suppressor in Nicotiana benthamiana leave. P19 construct was expressed alone as a control. dPPRerpl2 was expressed from two vectors (pGWB2 and pMDC32).
We extracted total RNA at 3 dpi from the experimental (3 biological replicates for each vector) and control (3 biologial replicates) samples for differential gene expression analysis by RNA-seq.

last: Hammani


title: Zebrafish embryos exposed to triadimefon for the detection of concentration and time dependent biomarkers for teratogenic effects

city: Hannover

first: Matthias

last: Wehr

address: Nikolai-Fuchs-Str. 1

institute: Fraunhofer ITEM

summary: The objectives of this study were to identify biomarkers for teratogenic response in a dose and time resolved manner and align the findings with morphological alterations found ZET assay. For this purpose triadimefon was selected as a model compound with teratogenic effects and known mode of action.

overall_design: Zebrafish embryos were exposed to 4 concentration levels of triadimefon and sampled for RNA sequencing at 4 timepoints below 120 hpf, covering different developmental stages of the embryo.

first: Sylvia

last: Escher


title: A live attenuated SARS-CoV-2 vaccine constructed by dual inactivation of NSP16 and ORF3a

city: Hong Kong

first: Chon Phin

last: Ong

address: L3-53, Laboratory Block, 21 Sassoon Road

department: School of Biomedical Sciences

country: Hong Kong

institute: The University of Hong Kong

summary: To generate a live attenuated SARS-CoV-2 vaccine through impeding or abrogation of NSP16 and ORF3a functions for sterilising immunity in host

overall_design: We performed gene expression profiling analysis using data obtained from RNA-seq from SARS-CoV-2 WT-, d16- or d16i3a-infected lung adenocarcinoma at 24 hours post-infection

first: Chon

middle: P

first: Zi-Wei

last: Ye

first: Dong-Yan

last: Jin


title: Menin is a Targetable Epigenetic Regulator in Glioblastoma (ChIP-Seq)

city: New York

first: Viviane

last: Tabar

state: NY

address: Sloan-Kettering Cancer Ctr., 1275 York Ave

institute: Memorial Sloan Kettering Cancer Center

summary: Glioblastomas (GBM) are highly lethal tumors that are refractory to treatment. Here we describe a novel approach to target the epigenetic landscape of GBM and destabilize the glioma progenitor program, leading to inhibition of tumor growth. This is achieved through disruption of the activities of menin, an orphan protein that we demonstrate to play a pro-oncogenic role in GBM.  Using pharmacologic and genetic tools, we identify HMGN1, a nucleosome binding chromatin architectural protein as a novel partner for menin. Disruption of this interaction via a newly designed small molecule mimics the major effects of knocking out MEN1, particularly leading to the suppression of H3K27 acetylation marks at genes critical for glioma progenitor identity, as well as promising therapeutic in vivo activity.  This work demonstrates a novel role for menin as an epigenetic co-regulator of maintenance and proliferation of glioma.

overall_design: Chromatin Immunoprecipitation DNA sequencing (ChIP-seq) for Histone H3 Lysine 27 acetylation (H3K27ac) is performed with MEN1-WT, MEN1-KO and MY-182 treated glioblastoma cell.

first: Yanhong

last: Yang

first: Richard

last: Koche


title: Menin is a Targetable Epigenetic Regulator in Glioblastoma (RNA-Seq)

overall_design: To investigate the downstream effect of menin and its new partner HMGN1, we performed RNA-seq of control cells, MEN1-KO cells, shHMGN1 cells from same glioblastoma cell line.

first: Yuhki

last: Saito


title: Extracellular vesicles alter trophoblast function in pregnancies complicated by COVID-19

city: Philadelphia

first: Thea

last: Golden

state: PA

address: 421 Curie Blvd Room 1213

department: Obstetrics and Gynecology

institute: University of Pennsylvania

summary: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and resulting coronavirus disease (COVID-19) causes placental dysfunction, which increases the risk of adverse pregnancy outcomes.  While abnormal placental pathology resulting from COVID-19 is common, direct infection of the placenta is rare.  This suggests that pathophysiology associated with maternal COVID-19, rather than direct placental infection, is responsible for placental dysfunction and alteration of the placental transcriptome.  We hypothesized that maternal circulating extracellular vesicles (EVs), altered by COVID-19 during pregnancy, contribute to placental dysfunction.  To examine this hypothesis, we characterized maternal circulating EVs from pregnancies complicated by COVID-19 and tested their effects on trophoblast cell physiology in vitro.  We found that the gestational timing of COVID-19 is a major determinant of circulating EV function and cargo.  In vitro trophoblast exposure to EVs isolated from patients with an active infection at the time of delivery, but not EVs isolated from Controls, altered key trophoblast functions including hormone production and invasion.  Thus, circulating EVs from participants with an active infection, both symptomatic and asymptomatic cases, can disrupt vital trophoblast functions.  EV cargo differed between participants with COVID-19 and Controls, which may contribute to the disruption of the placental transcriptome and morphology.  Our findings show that COVID-19 can have effects throughout pregnancy on circulating EVs and circulating EVs are likely to participate in placental dysfunction induced by COVID-19.

overall_design: There are 3 sets of RNAseq; 1) placenta biopsy RNAseq, 2) BeWo cell RNAseq, 3) extracellular vesicle (EV) RNAseq.  The RNA-related methods for placenta and Bewo cell RNAseq are the same.  The RNA-related methods for EV RNAseq are different.  The transcriptome was analyzed to measure the effect of COVID-19 during pregnancy on the placenta and circulating EVs.  Placenta biopsies were collected at delivery from controls (no known SARS-CoV-2 infection (C), resolved infection in the first (R1), second (R2), and third (R3) trimester, and active infection (AI) at the time of delivery.  RNA sequencing was also performed to analyze the transcriptome of BeWo cells exposed in vitro to plasma EVs isolated from subjects with an active infection (BCD) or controls (BCC).  Finally, the transcriptome of plasma-derived EVs from controls (C), resolved infection in the first (R1), second (R2), and third (R3) trimester, and active infection (AI) at the time of delivery.

first: Sneha

last: Mani

first: Rebecca

middle: L

last: Linn

first: Rita

last: Leite

first: Natalie

middle: A

last: Trigg

first: Annette

last: Wilson

first: Lauren

last: Anton

first: Monica

last: Mainigi

first: Colin

middle: C

last: Conine

first: Brett

last: Kaufman

first: Jerome

middle: F

last: Strauss

first: Samuel

last: Parry

last: Simmons


title: Microbial infection instigates tau-related pathology in Alzheimer's disease via activating neuroimmune cGAS-STING pathway

city: Shanghai

first: Erlin

last: Wang

state: Shanghai

address: 748 Zhongshan Middle Road, Songjiang District, Shanghai

department: Songjiang Hospital

institute: Shanghai Jiao Tong University School of Medicine

summary: Microbial infection, the strong trigger to directly induce inflammation in brain, is long considered a risk factor of Alzheimer's disease (AD), but how these infections contribute to neurodegeneration remains underexplored. To examine the effect of herpes simplex virus type 1 (HSV-1) infection on tauopathy in local hippocampus of P301S mice, we utilized a modified HSV-1 strain (mHSV-1) potentially relevant to AD, we found that its infection promotes tau-related pathology in part via activating neuroimmune cGAS-STING pathway in the tau mouse model. Specifically, Sting ablation causes the detectable improvement of neuronal dysfunction and loss in P301S mice, which is causally linked to lowered proinflammatory status in the brain. Administration of STING inhibitor H-151 alleviates neuroinflammation and tau-related pathology in P301S mice. These results jointly suggest that herpesviral infection, as the vital environmental risk factor, could induce tau-related pathology in AD pathogenesis partially via neuroinflammatory cGAS-STING pathway.

overall_design: Analysis and comparison of hippocampal transcriptomes in P301S mice between uninfected and HSV-1 infected conditions.

first: Xiaoxu

last: Yan

first: Meng

last: Zhao

first: Guanqin

last: Ma

first: Xiang-Xiong

last: Xu

first: Jie-Bin

first: Xiaohong

last: Li

first: Xueling

first: Jianxiong

last: Zeng


title: A role for astrocytic miR-129-5p in Frontotemporal Dementia

city: Gottingen

first: Andre

last: Fischer

state: NS

address: Von Sieboldstr 3a

department: Epigenetic Mechanisms in Dementia

institute: German Center for Neurodegenerative Diseases (DZNE)

summary: Frontotemporal dementia is a debilitating neurodegenerative disorder characterized by frontal and temporal lobe degeneration, resulting in behavioral changes, language difficulties, and cognitive decline. In this study, smallRNA sequencing was conducted on postmortem brain tissues obtained from FTD patients with GRN, MAPT, or C9ORF mutations, focusing on the frontal and temporal lobes. Our analysis identified miR-129-5p as consistently deregulated across all mutation conditions and brain regions. Functional investigations revealed a novel role of miR-129-5p in astrocytes, where its loss led to neuroinflammation and impaired neuronal support functions, including glutamate uptake. Depletion of miR-129-5p in astrocytes resulted in the loss of neuronal spines and altered neuronal network activity. These findings highlight miR-129-5p as a potential therapeutic target in neurodegenerative diseases and also sheds light on the role of astrocytes in Frontotemporal dementia pathogenesis.

overall_design: miR-129-5p knockdown was performed in the primary neurons as well as in primary astrocytes, followed by gene expression profiling analysis of RNA-Seq data.

first: Lalit

last: Kaurani

first: Farahnaz

last: Sananbenesi


title: Long term exposure of PB-MP has no effect on the metabolism of mice

city: seoul

first: sungguan

last: hong

institute: Chung-Ang

summary: Microplastics are defined as plastics ranging in size from 0.1μm to 5mm. Currently, research is being conducted across various fields to examine the effects of microplastics. Some studies demonstrated negative impacts on cells and mice. However, there is a lack of research on the effects by long-term exposure to microplastics. Most of the papers evaluated cytotoxicity with period of less than 2 months. Therefore, in this study, we investigated the potential issues that may arise from prolonged exposure through food mixed with Polypropylene black microplastic (PB-MP) for over a year. We divided our study into short, mid, and long-term periods to assess cytotoxicity through Glucose tolerance test, Insulin tolerance test, analysis of insulin and c-peptide levels, hanging, grip, treadmill, Y-maze and open field tests, Respiratory Exchange Ratio, Energy Expenditure, Activity, and body composition. Through this, we comprehensively examined potential issues related to mouse behavior, muscle, metabolism and other factors. After dissection, RNA sequencing was carried out to investigate the effects on genes. For further verification, RT-qPCR was conducted. To summarize, our study provides evidence suggesting that treatment of microplastics for a short term has adverse effects, but with prolonged exposure, their effects tend to diminish.

overall_design: To assess the impact of prolonged Polypropylene black Microplastic (PB-MP) exposure on mice, hepatic gene expression profiles were analyzed.

first: Bokyung

last: Kim

first: Gyeong

middle: B

last: Song

first: Jeein

last: Hong

first: Gijeong

last: Woo

first: Mi

middle: J

last: Choi

first: Sungguan


title: Long term expousre of PE-MP has no effect on the metabolism of mice

summary: Microplastics are defined as plastics ranging in size from 0.1μm to 5mm. Currently, research is being conducted across various fields to examine the effects of microplastics. Some studies demonstrated negative impacts on cells and mice. However, there is a lack of research on the effects by long-term exposure to microplastics. Most of the papers evaluated cytotoxicity with period of less than 2 months. Therefore, in this study, we investigated the potential issues that may arise from prolonged exposure through food mixed with Polyethylene microplastic (PE-MP) for over a year. We divided our study into short, mid, and long-term periods to assess cytotoxicity through Glucose tolerance test, Insulin tolerance test, analysis of insulin and c-peptide levels, hanging, grip, treadmill, Y-maze and open field tests, Respiratory Exchange Ratio, Energy Expenditure, Activity, and body composition. Through this, we comprehensively examined potential issues related to mouse behavior, muscle, metabolism and other factors. After dissection, RNA sequencing was carried out to investigate the effects on genes. For further verification, RT-qPCR was conducted. To summarize, our study provides evidence suggesting that treatment of microplastics for a short term has adverse effects, but with prolonged exposure, their effects tend to diminish.

overall_design: To assess the impact of prolonged Polyethylene Microplastic (PE-MP) exposure on mice, hepatic gene expression profiles were analyzed.

first: Gyeong-Bae

first: Mi-Jung


title: Long term expousre of PS-MP has no effect on the metabolism of mice.

summary: Microplastics are defined as plastics ranging in size from 0.1μm to 5mm. Currently, research is being conducted across various fields to examine the effects of microplastics. Some studies demonstrated negative impacts on cells and mice. However, there is a lack of research on the effects by long-term exposure to microplastics. Most of the papers evaluated cytotoxicity with period of less than 2 months. Therefore, in this study, we investigated the potential issues that may arise from prolonged exposure through food mixed with Polystyrene microplastic (PS-MP) for over a year. We divided our study into short, mid, and long-term periods to assess cytotoxicity through Glucose tolerance test, Insulin tolerance test, analysis of insulin and c-peptide levels, hanging, grip, treadmill, Y-maze and open field tests, Respiratory Exchange Ratio, Energy Expenditure, Activity, and body composition. Through this, we comprehensively examined potential issues related to mouse behavior, muscle, metabolism and other factors. After dissection, RNA sequencing was carried out to investigate the effects on genes. For further verification, RT-qPCR was conducted. To summarize, our study provides evidence suggesting that treatment of microplastics for a short term has adverse effects, but with prolonged exposure, their effects tend to diminish.

overall_design: To assess the impact of prolonged Polystyrene Microplastic (PS-MP) exposure on mice, hepatic gene expression profiles were analyzed.


title: Fulvic acid exhibits antitumor effects in ovarian cancer cells by upregulating CYP1A1 expression

city: Tai’an

first: Fangjun

last: Ding

address: 249 Chuangye Road, High-tech Zone, Feicheng City, Shandong Province

institute: Shandong Agricultural University Fertilizer Science & Technology Co., Ltd

summary: Humic substances are a mixture of natural organic macromolecular compounds, mainly fulvic acid (FA) (soluble in alkali, water, and acid) and humic acid (soluble in alkali but insoluble in water and acid). However, to the best of our knowledge, its antitumor effect remains indeterminate. Herein, we aimed to explore the effects and mechanisms of FA in ovarian cancer cells.

overall_design: SK-OV-3 cells were cultured in a culture medium with or without 100-μg/ml FA for 48 h and harvested for RNA sequencing.

first: Min

last: Chen

first: Ming

last: Cheng

first: Jun

last: Guo

first: Chenchen

last: Shao

first: Wenwen

last: Liang

first: Yi

last: Tang


title: Integrative genomic approach identifies glial transcriptomic dysregulation in the cortex of individuals with Alcohol Use Disorder

city: Austin

first: Anna

last: Warden

state: TX

address: 2500 Speedway

institute: University of Texas at Austin

summary: Nuclei were isolated from human postmartum brain frozen dorsolateral prefrontal cortex samples of AUD and control individuals. Libraries were prepared with 10X Genomics platform and sequenced using NovaSeq 6000. Post-filtering and site integration resulted in 464, 716 nuclei for downstream analysis.

overall_design:
Single nucleus RNA sequencing (snRNA-seq) from dorsolateral prefrontal cortex of 36 AUD and 37 control individuals.

UPDATE [Apr-25-2025] The numberings in the Sample titles and processed data file names were updated as per the GSE247416_old_new_numberings.xlsx file. The data did not change.

middle: S

first: Nihal

last: Salem

first: Eric

last: Brenner

first: Greg

middle: T

last: Sutherland

first: Julia

last: Stevens

first: Manav

last: Kapoor

first: Alison

middle: G

last: Goate

first: R

middle: D

last: Mayfield


title: Genomic and transcriptomic profiles underlying the effect of SETD1A disruption on human neurodevelopmental trajectories (scRNA-Seq)

city: NY

first: zhixiong

last: sun

address: 3908 pardes building, NYSPI

department: Psychiatry

institute: Columbia University

summary: To dissect, in more detail, cell population alterations and examine in situ genotypic differences in transcriptomic and regulatory profiles during neurogenesis and neuronal differentiation, we used single cell RNA sequencing (scRNA-seq) to profile cell type composition and molecular signatures of FOs derived from mutant and control iPSC lines at DIV70

overall_design: DIV70 forebrain organoids per sample dissociated using papain digestion and analyzed using scRNAseq.

first: Zhixiong

last: Sun

first: Bin

last: Xu

first: Joseph

last: Gogos


title: Differential pathogenic and molecular features in neurological infection of SARS-CoV-2 Omicron BA.5.2 and BA.2.75 and Delta

first: Erlin

last: Wang

summary: The Coronavirus disease 2019 (COVID-19) pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) remains a global threat, exacerbated by the emergence of viral variants. Two variants of SARS-CoV-2, Omicron BA.2.75 and BA.5, led to global infection peaks between May 2022 and May 2023, yet their precise characteristics in pathogenesis are not well understood. In this study, we compared these two Omicron sublineages with the previously dominant Delta variant using a human angiotensin-converting enzyme 2 knock-in mouse model. As expected, Delta exhibited higher viral replication in the lung and brain than both Omicron sublineages which induced less severe lung damage and immune activation. In contrast, the Omicron variants especially BA.5.2 showed a propensity for cellular proliferation and developmental pathways. Both Delta and BA.5.2 variants, but not BA.2.75, led to decreased pulmonary lymphocytes, indicating differential adaptive immune response. Neuroinvasiveness was shared with all strains, accompanied by vascular abnormalities, synaptic injury, and loss of astrocytes. However, Immunostaining assays and transcriptomic analysis showed that BA.5.2 displayed stronger immune suppression and neurodegeneration, while BA.2.75 exhibited more similar characteristics to Delta in the cortex. Such differentially infectious features could be partially attributed to the weakened interaction between Omicron Spike protein and host proteomes decoded via co-immunoprecipitation followed by mass spectrometry in neuronal cells. Our present study supports attenuated replication and pathogenicity of Omicron variants but also highlights their newly infectious characteristics in the lung and brain, especially with BA.5.2 demonstrating enhanced immune evasion and neural damage that could exacerbate neurological sequelae.

overall_design: Comparative Transcriptomic Profiling of Lung and Cortex in hACE2 Mice Infected with SARS-CoV-2 Delta, BA.2.75, and BA.5 Variants.

first: Qiao-Jiang

last: Yang

first: Xiang-Xiong

first: Qing-Cui

last: Zou

first: Yanghaopeng

last: Long

first: Guanqin

last: Ma

first: Zhong-Hua

last: Deng

first: Jie-Bin

last: Zhao

first: Ming-Hua

last: Li

first: Jianxiong

last: Zeng


title: Single-Cell Transcriptome Atlas of Human Mesenchymal Stem Cells Derived from Umbilical Cords during Passaging

first: Qiancheng

last: Xiao

address: Building 25, No. 1188, LIANHANG Road, Pujiang Town, Minhang District, Shanghai

institute: Shanghai OE Biotech Co., Ltd

summary: The immunosuppressive properties of mesenchymal stromal cells (MSCs) derived from umbilical cords have been clinically used to treat many clinical diseases, such as graft-versus-host disease (GVHD). Due to batch-to-batch variability, the obtained results are frequently variable and may depend on the different MSC origin as well as harvesting and culture procedures. The quality control of MSC product to treat many clinical diseases is still ambiguous. The recent emergence of single-cell RNA sequencing (scRNA-seq) methods allows us to investigate cellular heterogeneity at single cell resolution and uncovers unknown mechanisms underlying diseases and tissue development. However, the cellular landscape of human umbilical cord-derived MSCs has barely been explored at single-cell resolution. .In summary, our work provides timely and exciting insights into MSC heterogeneity on multiple levels. In addition to resource value, this MSC atlas taxonomy provides a comprehensive understanding of cellular heterogeneity, revealing the potential improvements in MSC-based therapeutic efficacy.

overall_design: Examination of 4 MSC samples from 2 donors using single-cell RNAseq at different cell passage.

first: Zheng


title: Single-cell transcriptome landscape suggests novel fingerprint of relapse in acute monocytic leukemia post transplantation

summary:
We analyzed transcriptome data from above 50K single leukemia bone marrow cells across 3 patients during newly diagnosed, complete remission and relapse stages. These 3 patients belong to M4 or M5, according to French-American-British classification.
We analyze heterogeneity of acute myeloid leukemia during progression and identify novel relapse subgroups in these heterogeneous populations.

overall_design: Since single-cell suspension was obtained from bone marrow of acute myeloid leukemia samples, we used the 10x Genomics Chromium platform to capture transcriptomes of single cells on barcoded mRNA capture beads for massively parallel scRNA-seq.

first: Ke

last: Sui


title: Effect of cardiac specific depletion of one allele of Mrps5 on gene expression in heart at postnatal day 4

city: Hang Zhou

first: Feng

last: Gao

address: Kaixuan road 268

department: Department of Cardiology

institute: Second Afliated Hospital, Zhejiang University School of Medicine

summary:
To investigate the function of reduction in Mrps5 expression in the regulation of cardiomyocyte proliferation and postnatal heart development, we established the mouse with cardiac specific depletion of one allele of Mrps5 through Cre-Loxp system by crossing Mrps5 fl/fl mouse with Myh6-Cre mouse.
We cross Mrps5 fl/fl mouse with Myh6-Cre mouse to obtain the Mrps5 fl/+;Myh6-Cre mouse and its control littermates Mrps5 fl/+ mouse. So that one allele of Mrps5 gene was depleted upon Myh6 gene promoter drivened Cre expression at the later stage of embyronic stage.
We then performed gene expression profiling analysis using data obtained from RNA-seq of Mrps5 fl/+; Myh6-Cre and Mrps5 fl/+ mouse hearts  at postnatal day 4.

overall_design: Comparative gene expression profiling analysis of RNA-seq data for Mrps5 fl/+; Myh6-Cre mouse hearts and its control littermates hearts at postnatal day 4. Each group has 4 biological replicates, the control group indicates as Ctrl_1, Ctrl_2, Ctrl_3, Ctrl_4 and the Mrps5 heterozygous group indicates as cHET_1, cHET_2, cHET_3, cHET_4.

first: Tian

last: Liang

first: Da-Zhi

first: Jinghai

last: Chen


title: Identification of signaling molecules associated with Failed Back Surgery Syndrome treated with spinal cord stimulation

city: Valencia

first: Angela

middle: L.

last: Riffo-Campos

state: Valencia

address: Avda. Blasco Ibáñes, 17

department: Department of Biochemistry and Molecular Biology

country: Spain

institute: University of Valencia, and INCLIVA

summary: Failed Back Surgery Syndrome (FBSS) is a relatively frequent entity that can cause a great limitation in the patients who suffer it. Spinal Cord Stimulation (SCS) is used in those patients refractory to conventional therapies. This project aims to identify new functional molecular bases, defined with transcriptomic and proteomic profiles represented differentially in the serum of a series of patients with chronic pain caused by FBSS. Identification of "omic" markers for the diagnosis and monitoring of the process of establishing and maintaining pain, as well as the assessment of these changes as evolutionary markers of disease or predictors in response to treatment with SCS.

overall_design: We have included 30 patients with refractory FBSS who were treated with a SCS system. 23 of them responded to the therapy and 7 didn´t respond; in those patients the SCS was removed after 15 days of treatment. 15 control patients (operated who did not develop FBSS) were also included. We obtained blood samples before implantation of the SCS (T0), 15 days after the implant (T3) and 2 months after the implant (T4)

first: Gustavo

last: Fabregat-Cid

first: Anushik

last: Harutyunyan

first: David

last: Albuquerque

first: Nieves

last: Prieto-Colodrero

first: Rebeca

last: Melero-Valverde

first: Raquel

last: Rodríguez-López

first: Ángela

first: Guillermo

last: Ayala


title: Trans-differentiation of outer hair cells into inner hair cells in the absence of INSM1

status: Public on Apr 16 2025

city: Chicago

first: Jaime

last: Garcia-Anoveros

address: 303 E Chicago Ave, Ward 10-070, Chicago, IL 60657

department: Anesthesiology

institute: Northwestern University

summary: The mammalian cochlea contains two types of mechanosensory hair cell that have different and critical functions in hearing. Inner hair cells (IHCs), which have an elaborate presynaptic apparatus, signal to cochlear neurons and communicate sound information to the brain. Outer hair cells (OHCs) mechanically amplify sound-induced vibrations, providing enhanced sensitivity to sound and sharp tuning. Cochlear hair cells are solely generated during development, and hair cell death—most often of OHCs—is the most common cause of deafness. OHCs and IHCs, together with supporting cells, originate in embryos from the prosensory region of the otocyst, but how hair cells differentiate into two different types is unknown. Here we show that Insm1, which encodes a zinc finger protein that is transiently expressed in nascent OHCs, consolidates their fate by preventing trans-differentiation into IHCs. In the absence of INSM1, many hair cells that are born as OHCs switch fates to become mature IHCs. To identify the genetic mechanisms by which Insm1 operates, we compared the transcriptomes of immature IHCs and OHCs, and of OHCs with and without INSM1. In OHCs that lack INSM1, a set of genes is upregulated, most of which are normally preferentially expressed by IHCs. The homeotic cell transformation of OHCs without INSM1 into IHCs reveals a mechanism by which these neighbouring mechanosensory cells begin to differ: INSM1 represses a core set of early IHC-enriched genes in embryonic OHCs and makes them unresponsive to an IHC-inducing gradient, so that they proceed to mature as OHCs. Without INSM1, some of the OHCs in which these few IHC-enriched transcripts are upregulated trans-differentiate into IHCs, identifying candidate genes for IHC-specific differentiation.

overall_design: RNA-seq of profiling of outer hair cells in the absence of Insm1 Het and KO mice at E18.5

first: Teerawat

last: Teerawat

first: Sarah

last: Lorenzen

first: Jorge

last: Cantú

first: Chuan Zhi

last: Foo

first: Ann

middle: K

last: Hogan

first: Freddie

last: Márquez

first: John

last: Clancy

first: Matthew

last: Schipma

first: Mary Ann

last: Cheatham

first: Anne

last: Duggan

last: García-Añoveros


title: Genomic and transcriptomic profiles underlying the effect of SETD1A disruption on human neurodevelopmental trajectories [ChIP-seq]

first: zhixiong

last: sun

summary:
To examine the genomic alteration by SETD1A deficiency, combining CRISPR/CAS9 genome editing and 3-Dimentional Cell Culture technology, we generated organoid models of the developing human cerebral cortex derived from isogenic human induced pluripotent stem cells (hiPSCs) modified to carry a SETD1A LoF schizophrenia risk mutation.
We then performed genomic profiling analysis using data obtained from CUT&Tag of WT and mutant cortical neurons at DIV70.

overall_design: Comparative binding occupancy profiling analysis of SETD1A for sorted GFP positive neurons of WT and mutant forebrain organoids at DIV70

first: Zhixiong

last: Sun

first: Bin

last: Xu

first: Joseph

last: Gogos


title: The non-coding RNA landscape associated with the malignant transformation of endometriosis into endometriosis-correlated ovarian cancer

city: Bologna

first: Gloria

last: Ravegnini

address: via Zamboni 33

country: Italy

institute: Alma Mater Studiorum - Università di Bologna

summary: Background. Endometriosis (EMS) is a chronic, gynecological condition affecting 6-10% of reproductive-age women. While these lesions are benign, ovarian EMS present cancer-like features, and can progress to endometriosis-correlated ovarian cancer (ECOC) through a multistep process. Given the regulatory role of miRNAs in gene expression and biological pathways, we aimed to identify miRNAs associated with the malignant transformation of ovarian EMS, which could serve as a potential diagnostic tool for the early identification of such patients. Methods. Global miRNA profiling was performed in patients with benign ovarian EMS (EMS-b) and  patients with ECOC. Differential expression analysis (DEA) of miRNAs between EMS-b, EMS tissues from patients with ECOC (EMS-k) and ECOC tissues was performed. Receiver Operating Characteristic (ROC) curves were built to evaluate the binary classification performance of significant miRNAs. Results. Comparison between EMS-b and EMS-k revealed 13 significantly deregulated miRNAs. Furthermore, when comparing ECOC and EMS-b we observed significant deregulation of 181 miRNAs. ROC analysis revealed a panel of seven upregulated miRNAs with accuracies above 0.7 in identifying EMS-k and EMS-b. Notably, four miRNAs (hsa-miR-200a-3p, hsa-miR-141-3p, hsa-miR-183-5p, hsa-miR-10a-5p) were consistently upregulated in both EMS-k and ECOC tissues. Conclusions. Our study identified a panel of miRNA biomarkers that may serve as potential candidates for the early detection of ECOC in patients previously diagnosed with ovarian EMS.

overall_design:
Global miRNA profiling was performed in patients with benign ovarian EMS (EMS-b) and  patients with ECOC.
case-control

first: Camelia

last: Coada


title: Neural representation of cytokines by vagal sensory neurons

city: Manhasset

first: timothy

last: Morgan

state: New York

address: 350 Community Drive

department: Feinstein Institutes

institute: Northwell

summary: The nervous system coordinates with the immune system to detect and respond to harmful stimuli. Inflammation is a universal response to injury and infection that involves the release of cytokines. While it is known that information about cytokines is transmitted from the body to the brain, how the nervous system encodes specific cytokines in the form of neural activity is not well understood. Using in vivo calcium imaging, we show that vagal sensory neurons within the nodose ganglia exhibit distinct real-time neuronal responses to inflammatory cytokines. Some neurons respond selectively to individual cytokines, while others encode multiple cytokines with distinct activity patterns. In a mouse model of colitis, inflammation increased the baseline activity of these neurons but decreased responsiveness to specific cytokines, reflecting altered neural excitability. Transcriptomic analysis of vagal ganglia from colitis mice revealed downregulation of cytokine signaling pathways, while neuronal activity pathways were upregulated. Thus, nodose ganglia neurons perform real-time encoding of cytokines at the first neural station in a body-brain axis, providing a new framework for studying the dynamic nature of neuroimmune communication.

overall_design: Bulk RNA-seq was performed on dissociated vagal ganglia from adult C57BL/6J mice (2–8 months old) given 4% DSS in drinking water for 7 days to induce colitis, compared to untreated controls. Left and right vagal ganglia were harvested on day 7 or 8, enzymatically dissociated, and purified cell suspensions were flash-frozen and submitted to Singulomics Corporation (Bronx, NY) for RNA extraction, library preparation and sequencing

first: Tomás

last: Huerta

first: Adrian

last: Chen

first: Saher

last: Chaudhry

first: Aisling

last: Tynan

first: Timothy

first: Kicheon

last: Park

first: Richard

last: Adamovich-Zeitlin

first: Bilal

last: Haider

first: Jian Hua

last: Li

first: Mitali

last: Nagpal

first: Stavros

last: Zanos

first: Valentin

last: Pavlov

first: Michael

last: Brines

first: Theodoros

first: Sangeeta

last: Chavan

first: Kevin

last: Tracey

first: Eric

middle: H

last: Chang


title: Genetic variation at transcription factor binding sites largely explains phenotypic heritability in maize

city: Duesseldorf

first: Thomas

last: Hartwig

address: University Street 1

institute: Heinrich-Heine University

summary: Comprehensive maps of functional variation at transcription factor (TF) binding sites (cis-elements) are crucial for elucidating how genotype shapes phenotype. Here, we report the construction of a pan-cistrome of the maize leaf under well-watered and drought conditions. We quantified haplotype-specific TF footprints across a pan-genome of 25 maize hybrids and mapped over two hundred thousand (epi)genetic variants (termed binding-QTL) linked to cis-element occupancy. Three lines of evidence support the functional significance of binding-QTL: i) coincidence with causative loci that regulate traits, including VGT1, ZmTRE1, and the MITE transposon near ZmNAC111 under drought; ii) bQTL allelic bias is shared between inbred parents and matches ChIP-seq results, iii) partitioning genetic variation across genomic regions demonstrates that binding-QTL capture the majority of heritable trait variation across ~72% of 143 phenotypes. Our study provides an auspicious approach to make functional cis-variation accessible at scale for genetic studies and targeted engineering of complex traits.

overall_design:
MOA-seq was performed in leaf blades of 25 maize F1 hybrids under well-watered and drought conditions.

Please note that each processed data file was generated from multiple replicates and thus linked as Series supplementary file. The sample_to_processed_data.readme.txt list which samples each file belongs to. We further note that all F1 MOA/RNA data was mapped to diploid genomes created by concatenating the B73 V5 genome with the respective paternal genome (NAM v1 / 2 genomes18, Mo17 CAU v1, W22 v220, A188 v119, and A619) with the accession ID added as prefix to the chromosome name.

first: Julia

last: Engelhorn

first: Samantha

last: Snodgrass

first: Amelie

last: Kok

first: Arun

last: Seetharam

last: Schneider

first: Tatjana

last: Kiwit

first: Ayush

last: Singh

last: Banf

first: Duong Thi Hai

last: Doan

first: Merritt

last: Khaipho-Burch

first: Daniel

middle: E

last: Runcie

first: Victor

last: Sanchez-Camargo

first: Rechien

last: Bader

first: Jorge Vladimir

last: Torres-Rodriguez

first: Guangchao

last: Sun

first: Maike

last: Stam

first: Fabio

last: Fiorani

first: Sebastian

last: Beier

first: James

last: Schnable

first: Hank

middle: W

last: Bass

first: Matthew

last: Hufford

first: Benjamin

last: Stich

first: Wolf

last: Frommer

first: Jeffrey

last: Ross-Ibarra


title: Optimized low-volume Plasmodium blood sample processing protocols for untargeted transcriptomics

city: Antwerp

first: Anna

last: Rosanas-Urgell

address: Nationalestraat 155

department: Department of Biomedical Sciences

institute: Institute of Tropical Medicine Antwerp

summary: As the importance of transcriptional variation and regulation for Plasmodium becomes more apparent, advances for non-falciparum species are hindered by our reliance on natural infections to study parasite biology. Untargeted transcriptomic research is also complicated by low parasite densities and high proportions of human genetic material, highlighting the need for optimized sample processing protocols. In this study, we used a P. knowlesi culture diluted in whole blood as a mock P. vivax natural infection to compare white blood cell, rRNA-, and globin depletion methods and RNA-seq library preparation kits to create an optimized protocol for low-volume sample processing.

overall_design:
Bulk RNA-seq of P. knowlesi mock natural infection samples (5,000 parasites/ul) processed using different combinations of white blood cell depletion methods (buffy coat removal after centrifugation (cent/pipette), Plasmodipur filter (plasmo), Plasmodipur filter + MACS column (PMACS), cellulose column (cellulose)) in comparison to a no filter control, library preparation kits (mRNA Illumina / Qiagen, total RNA Qiagen) and globin/rRNA depletion methods.
Please note that, since there was no ethical approval for sharing the human component,  filtered parasite-only fastq files are provided as raw data and the count tables do include the human component as described in the data processing description.

first: Erin

last: Sauve

first: Johanna Helena

last: Kattenberg

first: Pieter

last: Moris

last: Guetens

last: Monsieurs


title: Pericytes promote more vascularization than stromal cells via an interleukin-6-dependent mechanism in microfluidic chips

city: Aachen

first: Julian

last: Gonzalez-Rubio

address: Forckenbeckstraße 55

department: BioTex

institute: RWTH University Aachen

summary: Pericytes are a key player in vascularization, protecting endothelial cells from external harm and promoting the formation of new vessels when necessary. However, pericytic identity and its relation with other cell types, such as mesenchymal stromal/stem cells, is highly debated. This study compares the role of pericytes and unselected stromal cells in vascularization using multichannel microfluidic chips. In both angiogenesis and vasculogenesis, pericytes promote more vessel formation than stromal cells. Pericytes can wrap around endothelial vessels acting as mural cells, while stromal cells remain separated. Whole-transcriptome sequencing confirms an upregulation of pro-vascularization genes in endothelial cell-pericyte co-cultures, while metabolism increases and inflammation decreases in stromal cell co-cultures. Treatment of stromal-endothelial cell co-cultures with either conditioned media or isolated extracellular vesicles from pericytes replicates the increase in vasculogenesis of the direct co-cultures. Cytokine quantification reveals that IL-6 is significantly increased in pericyte conditions. Blocking it with siltuximab results in a reduction of pericyte vasculogenic potential comparable to stromal cell levels, revealing that pericyte pro-vascularization is mediated by IL-6. This study provides new insights into the relationship between pericytes and endothelial cells and the elusive identity of mesenchymal stromal cells. These findings are relevant for both vascular biology and tissue engineering.

overall_design: We prepared 3D co-cultures of endothelial cells and supporting cells in fibrin gels. The supporting cells were either adipose tissue-derived stromal cells (ASC) or adipose tissue-derived pericytes. The endothelial cells were human umbilical vein endothelial cells (HUVECs). The cells were in the gel in a 1:2 ratio (5x10^6 Supporting Cells and 10x10^6 HUVECs). The gels were cultured for 10 days with EGM MV2 media (PromoCell). The gels were minced and the RNA was isolated for a comparative RNA study.

first: Hannah

last: Kubiza

first: Yong

last: Xu

first: Hiltrud

last: Koenigs-Werner

first: Mona Sophie

last: Schmitz

first: Stefan

last: Jockenhoevel

first: Michaela

last: Schedel

first: Christian

last: Apel

last: Cornelissen

first: Anja Lena

last: Thiebes


title: Genomic and transcriptomic profiles underlying the effect of SETD1A disruption on human neurodevelopmental trajectories

first: zhixiong

last: sun

summary:
To examine the transcriptomic alteration by SETD1A deficiency, combining CRISPR/CAS9 genome editing and 3-Dimentional Cell Culture technology, we generated organoid models of the developing human cerebral cortex derived from isogenic human induced pluripotent stem cells (hiPSCs) modified to carry a SETD1A LoF schizophrenia risk mutation.
We then performed gene expression profiling analysis using data obtained from RNA-seq of WT and mutant cortical neurons at DIV70.

overall_design: Comparative gene expression profiling analysis of RNA-seq data for sorted GFP positive neurons of WT and mutant forebrain organoids at DIV70

first: Zhixiong

last: Sun

first: Bin

first: Joseph

last: Gogos


title: Next-Generation Mapping of the ACINUS-Mediated Alternative Splicing Machinery and Its Regulation by O-glycosylation in Arabidopsis

city: Palo Alto

first: Shouling

address: 260 Panama St

department: Department of Plant Biology

institute: Carnegie Institution at Stanford

summary: Alternative splicing (AS) is a key mechanism of gene regulation, but the full repertoire of proteins involved and the regulatory mechanisms governing this process remains poorly understood. Using TurboID-based proximity labeling coupled with mass spectrometry (PL-MS), we comprehensively mapped the Arabidopsis AS machinery, focusing on the evolutionarily conserved splicing factor ACINUS, its paralog PININ, and the stable interactor SR45. Our analysis identified a high-confidence list of 298 components, including both established and novel interactors, providing strong evidence that alternative splicing is coupled to transcription and that multiple RNA processing steps occur simultaneously in plants. Selected interactors were validated through AS readouts and phenotypic analysis. Furthermore, a systematic evaluation of O-glycosylation double mutants revealed that SECRET AGENT (O-GlcNAc transferase) and SPINDLY (O-fucose transferase) modulate AS through both ACINUS-dependent and -independent pathways.

overall_design: We used whole seedlings of Arabidopsis thaliana  to explore the transcriptomic and alternative splicing changes between WT, acinus pinin, spy-4, Dex inducible SEC RNAi spy-4 lines ( mock- and Dex-treated). Four biological replicates were included for each sample type.

first: Andres V

last: Reyes

first: Shane

last: Carey

first: Sumudu S

last: Karunadasa

first: Wen-Dar

last: Lin


title: Sulfasalazine disrupts the interaction between TNFα and TNFR1 thus inhibiting NF-kB signaling activation to promote bone fracture healing

city: Jinan

first: Jingwei

last: Liu

state: State...

address: Wenhuaxi Rd 107#, Lixia District

institute: Qilu Hospital of Shandong University

summary: Fracture is one of the most common types of traumas. It is of great necessity to explore alternative therapies to boost bone fracture healing process. The aim of this study is to elucidate the role of sulfasalazine in bone fracture healing process. The role that sulfasalazine played in osteogenesis was investigated using MC3T3-E1 in vitro and in murine femoral fracture model in vivo. Western blotting, flow cytometry, RNA sequencing, Calcein AM/PI staining, Alizarin Red S staining, ALP activity assay, transmission electron microscope (TEM), H&E staining, immunohistochemistry (IHC), immunofluorescence (IF) and Surface plasmon resonance (SPR) analysis were performed in this study. Sulfasalazine failed to elicit ferroptosis and could antagonize apoptosis in osteoblasts within acceptable dose manner. Moreover, sulfasalazine promoted osteogenic differentiation. Furthermore, sulfasalazine was identified to inhibit inflammation by declination of inflammatory biomarkers. Besides, TNFα was verified as a potential downstream target for sulfasalazine and the adverse effect of TNFα on osteogenic differentiation could be largely salvaged by sulfasalazine due to direct binding between these two molecules. RNA-seq further implied decreased transcription of genes related to NF-κB pathway in sulfasalazine-treated osteoblasts. This was further verified by dampened p65 nuclear translocation. In vivo study showed sulfasalazine could promote fracture healing as evidenced by increased callus formation and better bone remodeling both histologically and radiologically. In conclusion, sulfasalazine accelerates osteogenic differentiation in vitro and promotes bone healing in vivo, instead of inducing cell death or vitiating fracture repair process. Sulfasalazine achieves this via direct binding to and thus inhibiting TNFα, which subsequently suppresses NF-κB p65 nuclear translocation. Therefore, sulfasalazine shows a promising outcome for the treatment of bone fracture.

overall_design: RNA-seq profiling of MC3T3-E1 cells of the sulfasalazine-treated group and the control group. The MC3T3-E1 cells in the sulfasalazine-treated group were treated with 200μM sulfasalazine for 24 hours before sample collection.

first: Cheng

last: Qiu


title: The essential role of connective-tissue cells during axolotl limb regeneration

city: Bar Harbor

first: Prayag

last: Murawala

state: ME

address: 159 Old Bar Harbor Rd, Bar Harbor, ME 04609

institute: MDI Biological Laboratory

summary: Axolotls (Ambystoma mexicanum) are known for their remarkable limb-regeneration abilities, which involve the formation of the blastema, a specialized structure consisting of progenitor cells contributed by all major tissues of the limb. Lateral plate mesoderm (LPM)-derived connective tissue (CT) cells dedifferentiate and play a critical role in blastema formation and subsequent limb regeneration. However, the complexity of the blastema’s cellular composition and the extent of CT participation and necessity have not been rigorously explored. To address this gap, we conducted 10x Xenium spatial transcriptomics using a selected array of probes and finding the cellular identity and molecular architecture of blastema during the first stages of limb regeneration

overall_design: To characterize the cellular and molecular architecture of blastema across limb regeneration, we generated a spatial transcriptomics dataset measuring the expression of 100 genes across 6 15 um cryosection from an uninjured limb, 3, 5, 7, 10, and 14 days post-amputation (dpa) using the 10X Genomics Xenium platform.

first: Damián

last: García-García

first: Dunja

last: Knapp

first: Minjoo

last: Kim

first: Katelyn

last: Jamwal

first: Heath

last: Fuqua

first: Ryan

last: Seaman

first: Riley

last: Grindle

first: Sergej

last: Nowoshilow

first: Maria

last: Novatchkova

first: Fred

last: Kolling

first: Joel

last: Graber


title: UVA-induced DNA damage and mutations in melanocytes and melanoma mutations

city: Grand Rapids

first: Gerd

last: Pfeifer

state: Michigan

address: 333 Bostwick Ave. NE., 5352W/Phase2

department: Center for Epigenetics

institute: Van Andel Research Institute

summary: Melanomas carry characteristic mutational signatures associated with solar UVB radiation-induced cyclobutane pyrimidine dimers (CPDs) that contain deaminated cytosines. However, there are several other mutation signatures, including those found in melanomas from non-sun-exposed body sites, that have unknown origins. To test if these signatures are linked to UVA radiation from the sun, we exposed human melanocytes to UVA and to UVB for comparison. We mapped DNA damage in the form of CPDs or 8-oxoguanine (8-oxoG) genome-wide at base resolution. We then determined mutational patterns in single melanocyte cell clones by whole genome sequencing. UVA-induced CPDs occurred overwhelmingly at TT sequences resembling melanoma signature SBS7d. We did not observe rising CPD levels after cessation of radiation (dark CPDs). However, the UVA-induced TT-CPDs did not score as mutagenic in the mutation analysis. 8-oxoG was present in melanocytes but was not substantially increased after UVA. G/C to T/A mutations were prominent in melanocyte single cell clones with no major shift after UVA radiation. These mutations matched SBS18, a signature present in melanomas. Our data suggest that melanocytes carry an endogenous but UVA-independent load of oxidative base lesions and their associated mutations that may be associated with a subset of melanoma mutations.

overall_design: UVA-induced DNA damage was mapped in genome-wide using CD-seq in human melanocyte cells.

first: Seung-Gi

last: Jin


title: Induced Pluripotent Stem Cell-Derived Exosomes Promote Peripheral Nerve Regeneration in a Rat Sciatic Nerve Crush Injury Model: A Safety and Efficacy Study

city: Wuhan

first: Xiaojian

last: Cao

state: Hubei

address: No.1095 Jiefang Avenue

department: Department of Rehabilination Medicne

institute: Tongji Hospital

summary: Peripheral nerve injury (PNI) is a major clinical and public health challenge that frequently results in significant functional impairment and permanent disability. However, most peripheral nerve injury-repairing strategies offer unsatisfactory clinical outcomes. Exosomes act as key mediators of the paracrine effects of induced pluripotent stem cells (iPSC-Exos), showing significant therapeutic promise for various conditions. Still, their efficacy and safety remain a major concern. Therefore, this study investigates the regeneration potential and safety of iPSC -Exos in a rat sciatic nerve crush injury model. Sendai virus vectors were used to reprogram peripheral blood mononuclear cells (PBMCs) from healthy donors into iPSCs. The cells were subsequently examined for pluripotency and karyotype integrity and validated using in vivo teratoma assays. iPSC-Exos were isolated and identified using transmission electron microscopy, nanoparticle tracking analysis, western blotting, and cell viability. In vivo, iPSC-Exos was injected directly at the injury site. Gait analysis, grip strength evaluation, and mechanical pain were measured preoperation and at 7, 14, 21, and 28 days postoperation. Animals' weight, hematology indexes, key organ weight, and histological changes were evaluated. Morphological analysis of regenerated nerve and muscle was examined. The immunofluorescence staining evaluated axon regeneration, remyelination, Schwann cells (SCs), and angiogenesis in the sciatic nerve at 2 and 4 weeks post-operation. Real-time PCR was used to assess gene-level expression associated with nerve regeneration. RNA sequencing (RNA-seq) was conducted to identify differentially expressed genes (DEGs) and pathways in experimental groups. PBMC-derived iPSCs exhibited Embryonic Stem cells-like morphology, showed pluripotency markers, preserved a normal karyotype, and induced teratomas, including tissues from all germ layers.  After isolating and validating exosomes, PKH26-labeled exosomes were efficiently absorbed by SCs and enhanced SCs proliferation in a concentration-dependent manner in vitro. Safety evaluations revealed no adverse effect on the overall body weight, organ weight, hematological parameters, or histological changes of key organs. Exosome injection significantly improved gait analysis, grip strength, pain response, gastrocnemius muscle atrophy, axonal regrowth, myelin formation, and neovascularization. Furthermore, quantitative Real-time PCR (qPCR) results indicated an increase in regeneration-associated transcripts. RNA-seq analysis identified the upregulation of genes involved in nerve repair, with enrichment of pathways such as PI3K-AKT signaling, focal adhesion, and calcium signaling.Exosomes derived from iPSCs show a safe, effective, and non-cell-based therapeutic approach for PNIs. Their ability to promote axonal regrowth, myelin formation, and angiogenesis demonstrates their potential for clinical applications in regenerative medicine.

overall_design: A:This experiment was divided into two parts, focusing on evaluating the effects of induced pluripotent stem cell-derived exosomes (iPSC-Exos) on peripheral nerve regeneration in a rat sciatic nerve crush injury model. Part 1: Collection and Characterization of iPSC and iPSC-Exosomes Blood Collection and PBMC preparation, reprogramming PBMCs to iPSCs, characterization of iPSCs, exosome isolation and characterization Part 2: Animal Study for safety and efficacy study. Animals and Experimental Groups: Forty-eight male Sprague-Dawley (SD) rats (5 weeks old, 204 ± 14 g) were randomly assigned to three experimental groups: Sham group (n=12): Sciatic nerve exposed but not crushed. Model + PBS group (n=18): sciatic nerve crushed and treated with10 μL of  PBS. Model + iPSC-Exosomes group (n=18): sciatic nerve crushed and treated with 10 μL of 100 μg/mL of iPSC-Exosomes.

first: Fatima

last: Aldali

first: Yujie

last: Yang

first: Chunchu

last: Deng

first: Xiangling

last: Li

first: Jia

last: Xu

first: Jianlin

last: Ding


title: Identifying critical lncRNAs in PBMCs linked to sepsis-induced immunosuppression using microarray analysis

city: Beijing

first: Wenjia

last: Zhang

address: Yinghua Road

institute: China-Japan Friendship Hospital

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

summary: This study aims to identify key long non-coding RNAs (lncRNAs) and their associated pathways in peripheral blood mononuclear cells (PBMCs) from sepsis immunosuppression patients. Using weighted gene co-expression network analysis (WGCNA), we have constructed a co-expression network to elucidate the molecular mechanisms underlying sepsis-induced immunosuppression. The study utilizes Agilent Human ceRNA Microarray 2019 to profile lncRNA expression in PBMCs from three sepsis patients and three healthy controls.

overall_design:
The study includes six samples: three from patients with sepsis-induced immunosuppression and three from healthy individuals.  Gene expression profiling was performed using the Agilent Human ceRNA Microarray 2019(4*180k,Design ID:086188).  Weighted gene co-expression network analysis (WGCNA) was applied to identify modules of co-expressed lncRNAs associated with sepsis.  KEGG pathway enrichment analysis and protein-protein interaction (PPI) network analysis were conducted to identify key pathways and hub genes.  RT-PCR was used for validation of selected lncRNAs and mRNAs.  External data validation was performed to corroborate the findings.

*** Submitter declares that raw data have been lost. ***


title: Unveiling a Novel in-vitro Model of Skin Inflamm-Aging: Validation of Terminalia chebula Extract and Supermolecular Bakuchiol for Reversal of Inflamm-Aging

city: Shanghai

first: Ying

address: No. 1755 Hongmeinan Road, Minhang District, Shanghai

institute: Better Way (Shanghai) Cosmetics Co. Ltd., China

summary: Introduction: Sensitive skin is characterized by skin barrier disruption which is usually prone to react to external stimuli including UV, air pollution as well as cosmetic allergens. Sensitive skin tends to react with oxidative stress factors that could further lead to skin inflammation resulting in inflamm-aging. But almost no inflamm-aging models for sensitive skin, so it is worth constructing a method to screen anti-inflammaging ingredients and products. Methods: An in-vitro macrophages-fibroblasts model was established to evaluate the anti-inflammaging effect of ingredients. M1 phenotype and aging-associated gene expression were recorded by qPCR test to validate the inflamm-aging model. RNA sequencing was used to further elaborate the inflamm-aging mechanism of two validated ingredients. Results and conclusion: A novel in-vitro model of sensitive skin inflamm-aging was constructed by applying M1 phenotype of THP-1 culture medium supernatant to introduce the cellular senescence of the fibroblast cells, which could be used to screen out anti-inflammaging ingredients. In this model, supramolecular bakuchiol could promote collagen COL1A1 and COL3A3 production and inhibit inflammatory factors by increasing anti-inflammatory gene transcription (PTX3, ADAM33, and PDLIM1), while Terminalia chebula extract can inhibit cell senescence by reducing transcription of MAP4K2, and inflammatory factors CCL3 accumulation.

overall_design: HSF cells were treated with 1640 complete medium, M1 type THP-1 cell culture supernatant, Chebulae Fructus extract + M1 type THP-1 cell culture supernatant, supramolecular psoralen + M1 type THP-1 cell culture supernatant for 3 days.


title: Autism spectrum disorder associated chromatin modifiers converge on transcription with sex-specific regulatory signatures

city: Philadelphia

first: Alekh

last: Paranjapye

state: Pennsylvania

address: 3400 Civic Center Blvd

department: Genetics

institute: University of Pennsylvania

summary: We sought to understand the transcriptional disruptions and functional impacts of the loss of 9 autism spectrum disorder (ASD) risk genes that encode transcriptional regulators in neurons. In addition to understanding how these signature converge or diverge, we aimed to study how sex could modulate these consequences.

overall_design: Neurons were cultured from wildtype e16.5 mouse embryos seperated by males and females. Cultures were infected with lentivirus containing shRNA against a nontargetted control or each of 9 genes to deplete targets. Neurons were lysed at day in culture 10 to collect total RNA. RNA was reverse transcribed and RNA-seq libraries were prepared. (n  =  3 per condition, per sex)

first: Rili

last: Ahmad

first: Erica

last: Korb


title: MMP12-dependent myofibroblast formation contributes to the nucleus pulposus fibrosis and intervertebral disc degeneration

city: Shenzhen

first: Eric

last: Sun

address: 1120 Lianhua Rd

institute: Peking University Shenzhen Hospital

summary: Human NP cells (NPC) are pre-conditioned in alginate for 7 days prior to monolayers expansion, and further treated by TGF-b1 for inducing fibroblastic differentiation. MMP12 is highly expressive in myofibroblastic NP cells, which depeltin by siRNA transfection results in a shift of fibroblastic/Cycling NP phenotypes towards epithelial/chondrogenic cells-like.

overall_design: RNA-seq profile of NPC and its induced MMP12 knockdown with treatment of TGF-b1 or not.

first: Sun

last: Yi

first: Leung

last: Victor


title: MiNK-215: Allogeneic FAP-CAR-IL15 iNKT therapy remodels tumor stroma to enhance anti-tumor immunity

city: New York

first: Alvaro

last: Sebastian

address: Inc. 149 Fifth Avenue Suite 500

institute: MiNK Therapeutics

summary: Cellular immunotherapies show remarkable efficacy against hematological malignancies; but face challenges against solid tumors largely attributed to the lack of tumor-specific antigens and immunosuppressive tumor microenvironment (TME). Cancer-associated fibroblasts (CAFs), expressing fibroblast activation protein (FAP) are key contributors in shaping this immunosuppressive landscape, yet effective targeting strategies remain an ongoing challenge. Here, we describe MiNK-215, a novel allogeneic human invariant natural killer T (iNKT) cell therapy, engineered to express a FAP-targeting chimeric antigen receptor (CAR) and secrete interleukin-15 (IL-15) to remodel the TME and enhance anti-tumor activity. MiNK-215 modulated multifunctional immune responses by enhancing T cell responsiveness, dendritic cell activation, M1 macrophage polarization, and tumor killing. In a lung tumor mouse model, MiNK-215 depleted FAP+ CAFs, enhanced antigen-specific T cell infiltration, and promoted durable anti-tumor immunity without off-target toxicity. These findings extended to human organoid models of treatment-refractory Microsatellite Stable Colorectal Cancer (MSS-CRC) liver metastases, establishing FAP-CAR iNKT cells as a promising strategy to overcome immunotherapy resistance in solid tumors.

overall_design: RNA-seq profiling of MiNK-215 versus FAP-CAR iNKTs without the IL-15 transgene following 4-hour co-culture with FAP+ A375 cells

first: Georgios

last: Antonopoulos

last: Sebastian-Yague

first: Eleni

last: Chantzoura


title: Subtyping Burkitt Lymphoma by DNA Methylation [EPIC]

city: Ulm

first: Selina

last: Glaser

address: Albert-Einstein-Allee 11

institute: Ulm University and Ulm University Medical Center

summary: Burkitt lymphoma (BL) is an aggressive germinal center B-cell-derived malignancy. Historically, sporadic, endemic, and immunodeficiency-associated epidemiological variants were distinguished which differ in the frequency of Epstein-Barr virus (EBV) association. Aiming at identifying subgroups based on DNA methylation patterns we here profiled 96 primary BL cases, 17 BL cell lines and 6 lymphoblastoid cell lines using Illumina BeadChip arrays. DNA methylation clustered the cases into each two subgroups according to EBV status, with each showing two underlying subgroups (EBV-positive: BL-mC1, BL-mC2 and EBV-negative: BL-mC3, BL-mC4). The subgroups BL-mC1/2 enriched for EBV-positive cases showed increased DNA methylation, epigenetic age and in part increased proliferation history compared to BL-mC3/4. CpGs hypermethylated in EBV-positive BLs were enriched for polycomb repressive complex 2 marks, while the CpGs hypomethylated in EBV-negative BLs were linked to B-cell receptor signaling. EBV-associated hypermethylation affected regulatory regions of genes frequently mutated in BL (e.g. CCND3, TP53), and impacted superenhancers, suggesting that hypermethylation may compensate for the lower mutation burden of oncogenic drivers in EBV-positive BLs. Though minor, but significant differences were also observed between EBV-positive endemic and sporadic cases (e.g. at the SOX11 and RUNX1 loci), our findings suggest that EBV status, rather than epidemiological variants, drive the DNA methylation-based subgrouping of BL.

overall_design: We collected 6 samples from patients with immunodeficiency-associated Burkitt lymphoma and 5 samples with splenomegaly due to chronic malaria infeciton in African individuals. The samples were analyzed using the MethylationEPIC BeadChip array.

first: Reiner

last: Siebert