title: Signatures of Innovation and Selection in the Extremotolerant Yeast Kluyveromyces marxianus

city: Berkeley

first: Kaylee

middle: Elizabeth

last: Christensen

state: CA

address: Koshland Hall rm 321

department: Plant and Microbial Biology

institute: UC Berkeley

summary: Organisms specialized to extreme environments can be the product of millions of years of evolutionary engineering and refinement. The underlying genetics can be quite distinct from those operating at earlier stages of trait innovation. In this work, we have developed the multistress-resistant yeast Kluyveromyces marxianus, which diverged from its closest relative >20 million years ago, as a model for interspecies comparative biology and genomics. In growth assays of the Kluyveromyces genus, we found that K. marxianus exhibited unique tolerance of high heat and a subset of chemical stress conditions. We then generated and analyzed omic profiles from across the genus to find molecular features associated with—and potentially causal for—K. marxianus traits. Expression profiling revealed divergent lipid processing and membrane transport programs in K. marxianus, borne out in changes in lipid utilization in experimental assays. Sequence analyses found robust evidence for expansions in gene families in the K. marxianus genome, most notably among transmembrane transporters and in metabolic enzymes. In molecular-evolution tests, we identified adaptive protein variants throughout the K. marxianus genome, among which plasma membrane transporters were over-represented. These data enable a model of the molecular mechanisms and evolutionary pressures underlying K. marxianus traits, including adaptive changes to transporters, lipid processing, and membrane functions mediating stress resistance.

sample_organism:
Kluyveromyces marxianus
Kluyveromyces lactis

overall_design: RNA-seq of K. marxianus and K. lactis cultures in control and stress (heat, MMS, ethanol, caffeine) conditions. Each condition has three biological replicates.

first: Aniliese

last: Deal

first: Jun-Ting Johnson

first: Abel

last: Duarte

first: Judith

middle: L

last: Edwards

first: Zhenzhen

last: Ma

first: Jasmine

last: Goodman

first: Sasha

middle: I

last: Padilla

first: Edyta

last: Szewczyk

first: Catherine

last: Rha

first: Rachel

middle: B

last: Brem


title: A STAT5B-driven mouse model of hepatosplenic γδ T cell lymphoma reveals therapeutic efficacy of JAK inhibitors

status: Public on Mar 12 2026

city: Vienna

first: Thomas

last: Eder

address: Veterinaerplatz 1

department: Department for Biological Sciences and Pathobiology

country: Austria

institute: University of Veterinary Medicine, Vienna

type: Expression profiling by high throughput sequencing

summary: Hepatosplenic T cell lymphoma (HSTL) is a rare, aggressive disease primarily affecting young adults. The disease progresses rapidly, with patients displaying low survival rates and poor responses to standard chemotherapy-based treatments. Currently no targeted therapies are available for HSTL, and pre-clinical models to test new treatment options have not been established. Hence, new models recapitulating HSTL are needed. The JAK-STAT signalling pathway is a key pathway dysregulated in HSTL and STAT5B N642H is the most frequent oncogenic mutation. Using a transgenic mouse model, we have previously validated STAT5B N642H as a strong driver of γδ T cell lymphoma. Here, we have established clonal, murine γδ T cell lymphoma cell lines driven by oncogenic STAT5B, which resemble key features of human HSTL. The IL-2 dependent cell line, C15, displays immunophenotypic features as well as commonly dysregulated gene expression profiles shared with patient-derived HSTL cell lines. C15 cells can be engrafted intravenously into immunocompetent mice to generate an aggressive HSTL-like disease. Recipient mice display an expansion of malignant γδ T cells causing hepatosplenomegaly and elevated alanine transaminase (ALT) and aspartate transaminase (AST) levels. Using these models, we tested the potential of JAK inhibition as a targeted treatment strategy for HSTL, with the clinically-approved JAK inhibitor upadacitinib displaying significant anti-tumor efficacy against HSTL cells in vitro and in vivo. Overall, we have developed a robust, accessible and faithful preclinical model of HSTL with the advantage of immune-competence, which can facilitate the study of physiological disease mechanisms and new (immuno)therapy strategies.

sample_organism:
Homo sapiens
Mus musculus

platform_organism:
Homo sapiens
Mus musculus

overall_design: We generated clonal mouse γδ T cell lymphoma cell lines harboring a STAT5B N642H mutation transgene. To compare their transcriptional profiles to human HSTL cells, we performed RNA-seq analysis using our mouse cell lines as well as two human HSTL cell lines that also harbor the STAT5B N642H mutation, DERL-2 and DERL-7. Differential gene expression analysis was performed for the mouse and human cell lines using primary murine γδ T cells and primary human CD3+ T cells as controls, respectively.

first: Neubauer

last: Heidi

first: Herling

last: Marco

first: Müller

last: Tony

first: Jungherz

last: Dennis

first: Eder

last: Thomas


title: Transcriptomic Changes in the Lacrimal Glands of a Sjogren's Disease Animal Model Highlight Key Molecular Mediators and Altered Biological Functions Underpinning Glandular Inflammation and Hypofunction

status: Public on Mar 11 2026

city: Boston

first: Danny

last: Toribio

state: MA

address: One Kneeland St

department: Basic and Clinical Translational Sciences

country: USA

institute: Tufts University School of Dental Medicine

summary: Sjogren’s disease (SjD) is a chronic autoimmune condition that targets the lacrimal glands (LGs), resulting in aqueous-deficient dry eye disease (DED). Insufficient or low-grade tear secretion onto the ocular surface affects the normal physiology of the cornea and conjunctiva and can result in ocular surface damage. Herein, we evaluated the transcriptomic profiles of diseased versus healthy LGs to investigate the underlying molecular mechanisms underscoring LG autoimmune inflammation and secretory hypofunction. The number of differentially expressed genes between NOR (diseased animal model/strain) and BALB/c (control strain) mice increased in correlation with the development and progression of dacryoadenitis. The most significantly upregulated pathways were primarily related to immune responses, emphasizing the activation of cellular and cytokine-mediated inflammatory responses. Several cytokines, transcription factors, and toll-like receptors were significantly predicted to drive most of the differential gene expression observed across our datasets. Biological processes involving the migration, recruitment, and activation of lymphocytes, but also lipid metabolism, were most significantly impacted in our disease model. Many of the identified dysregulated genes and affected biological functions were similarly regulated in the differential expression datasets of other transcriptomic based studies of SjD patients and mouse models. Taken together, our data reveals that chronic inflammation induces significant alterations to the LG transcriptome, promoting the recruitment of immune cells into the LG and the overactivation of inflammatory responses that severely impedes normal secretory function. Future studies targeting some of the discovered key dysregulated molecules/pathways could open up potential therapeutic avenues for the treatment of chronic LG inflammation and secretory hypofunction.

overall_design: Bulk RNA-seq profiling of lacrimal glands removed from NOR/LtJ mice (Sjogren's disease mouse model) and sex- and age-matched BALB/c controls (normal, wild-type control for the NOD/NOR strains). Three biological replicates were used for the NOR and BALB/c strains at three different timepoints: 3-weeks of age (pre-disease stage), 8-weeks of age (early disease onset), and 16-weeks of age (intermediately advanced disease stage).

first: Junji

last: Morokuma

first: Albert

last: Tai

first: Driss

last: Zoukhri


title: Whole-Protein Screening and Multi-Modal Profiling of Antigen-Specific CD4+ T Cells at Single-Cell Resolution

city: Seattle

first: Rongyu

last: Zhang

state: WA

address: 401 Terry Ave N

institute: ISB

summary: Systematic whole-protein screening and comprehensive profiling of antigen-specific CD4+ T cells are crucial for advancing vaccine design and cancer immunotherapies, yet remain technically challenging. Here, we present a high-throughput platform that utilizes large-scale class II single-chain trimer libraries to detect antigen-specific CD4+ T cells, while simultaneously profiling their antigen specificity, TCRα/β sequences, MHC restriction, whole transcriptomes, and patient/timepoint origins at single-cell resolution. Upon rigorous platform validation, we screened the full SARS-CoV-2 spike receptor binding domain in a longitudinal cohort of 22 participants, identifying 2,188 antigen-specific CD4+ T cells and revealing key metrics defining the immunogenicity of class II-restricted viral antigens. We further extended the platform to whole-protein screening of HPV-16 E6/E7 in a cohort of precancerous patients, uncovering HPV-specific CD4 TCRs that, upon extensive characterization, demonstrated strong therapeutic potential. By integrating high-throughput antigen screening with high-dimensional, multi-modal cellular characterization, our approach provides an unprecedented window into CD4+ T cell immunity, potentially guiding vaccine design and next-generation TCR-based cancer immunotherapies.

overall_design: RNA-seq profiling of antigen-specific CD4+ T cells identified through single-chain trimer (SCT) dextramers to characterize the immunological states of cells in response to SARS-CoV-2 and HPV-16 infections at various timepoints.


title: KLF2 overrides the resident memory CD8 T cell differentiation program, in opposition to KLF3

status: Public on Mar 10 2026

city: Minneapolis

first: Christine

middle: H

last: O'Connor

address: 117 Pleasant St. SE

department: Minnesota Supercomputer Institute

institute: University of Minnesota

summary: Numerous transcriptional regulators have been associated with the differentiation pathways that lead to recirculating versus tissue-resident memory T cells. However, it is unclear whether independent, coordinated expression of these regulators is required to determine residency versus recirculation, or whether there is a hierarchy, with some factors playing a dominant role in controlling T cell trafficking. We report that ablation of the gene encoding Kruppel-like factor 2 (KLF2) during CD8+ T cell activation leads to rapid transcriptional reprograming, such that effector T cells fail to recirculate and prematurely acquire canonical phenotypic and transcriptional characteristics of resident memory cells (TRM). Klf2-deficient memory CD8+ T cells retained the capacity to undergo recall responses, including in vivo pathogen control. These data suggest KLF2 diverts CD8+ T cells from the TRM differentiation program. In contrast, ablation of another member of the KLF family, KLF3, enhanced differentiation of some recirculating T cell subsets and limited production of TRM in lymphoid tissues. However, both KLF2 and KLF3 were required for differentiation of long-lived effector cells, suggesting cooperation between these factors in some situations. These findings indicate KLFs occupy a central nexus in coordinating activated CD8+ T cell differentiation and trafficking.

overall_design: Congenically distinct WT or KLF2-GFP P14 CD8+ T cells were negatively enriched from spleen and activated with plate bound α-CD3 and α-CD28 with rhIL-2 for 48 hours, and then electroporated with sgRNAs/Cas9 complexes for target (Klf2 or Klf3) or control (Cd19 or Thy1) genes through a Lonza 4DNucleofector X Unit, using published conditions (Seki et al. 2018). Following culture in rhIL-2 for 24-48h, 5x10e4 CRISPR-modified cells were co-adoptively transferred into congenically distinct host mice, which received LCMV-Arm infection (2x10e5 PFU) within 2h of transfer. CRISPR modified donor P14 CD8+ T cells were FACS sorted from the spleen, 8- or 25-days post LCMV infection, RNA isolated and submitted for sequencing through the University of Minnesota Genomics Center.

first: Taylor

middle: A

last: DePauw

first: Kexin

last: Gai

first: Jian

last: Shen

first: Nicholas

middle: J

last: Maurics

first: Ka Hyun

last: Rhee

first: Weiguo

last: Cui

first: Changwei

last: Peng

first: Stephen

middle: C

last: Jameson


title: Single-cell chromatin profiling reveals dynamic regulatory logic and enhancer elements in brain and retina development

city: Philadelphia

first: Bushra

last: Raj

state: PA

address: 421 Curie Boulevard

institute: University of Pennsylvania

type: Genome binding/occupancy profiling by high throughput sequencing

summary: Cell type identity in the nervous system is encoded within cis-regulatory landscapes that integrate transcription factor activity with chromatin accessibility. However, how these regulatory programs are organized and remodeled during post-embryonic neural development remains poorly understood. We generate a temporally resolved single-cell chromatin accessibility atlas of ~95,000 zebrafish brain and retina nuclei spanning larval, juvenile, and adult stages. We define 212 discrete chromatin states and uncover widespread, cell type-specific chromatin reorganization across development. By integrating with transcriptomic data, we link motif accessibility to transcription factor expression and identify regulatory programs that are either maintained or reconfigured during post-embryonic development of each cell type. Leveraging this atlas, we systematically identify and functionally validate candidate enhancers in vivo. Focusing on the slc1a3b locus in radial glia, we define evolutionarily conserved, compact enhancer modules that act combinatorially to drive gene expression. Together, these findings provide a systems-level framework for decoding neural regulatory logic and enable functional dissection of conserved cis-regulatory programs in the vertebrate nervous system.

overall_design: scATAC-seq profiling of wildtype, TL/AB zebrafish brain and eyes.  Dissection of zebrafish whole heads at 3 dpf and isolated zebrafish brain and eyes at 21 dpf and adult (5mpf). Lens and cornea were removed during dissection of adult eyes to enrich for retinal populations.

first: Jessie

middle: E

last: Greenslade

first: Hemagowri

last: Veeravenkatasubramanian

first: Marisa

last: Reed


title: An In Vitro Functional Characterization of the Cholesterol-Transforming Blautia hominis Strain HA2291 Isolated from the Human Gut

city: 青岛 Qingdao

first: Warren

last: Chanda

state: Shandong Province

address: No. 72 Beihai road, Jimo District

department: State Key Laboratory of Microbial Technology

country: China

institute: Shandong University

summary: Cholesterol is an essential lipid required for membrane structure and normal physiological functions. However, dysregulation of cholesterol homeostasis, manifesting as hypercholesterolemia, can precipitate a range of metabolic and cardiovascular diseases. Blautia species are important gut commensals, but their role in cholesterol metabolism remains poorly defined. Methods: A total of 63 Blautia strains isolated from human fecal samples were screened for cholesterol conversion using the o-phthalaldehyde colorimetric assay in cholesterol-containing media with or without oxgall. Cholesterol removal by live and heat-inactivated cells was compared. Metabolomic, transcriptomic, and proteomic analyses were employed to investigate molecular mechanisms and involved genes. Results: Nine strains significantly lowered cholesterol levels (live cells: 31–78%; heat-inactivated cells: 8–64%), with the B. hominis strain HA2291, the Blautia sp. strain HA3515, and the B. coccoides strain HA4419 showing the strongest activity. Oxgall increased cholesterol removal by live cells to 74–83%, indicating bile-tolerant metabolism activity. Metabolomic profiling revealed that B. hominis HA2291 transformed cholesterol into cholest-4-en-3-one and epicholestanol. An SCP2-like protein, RS03310, was identified as a candidate cholesterol-interacting factor; its recombinant form catalyzed measurable NAD+-dependent cholesterol oxidation in vitro. Conclusions: Blautia hominis HA2291 may employ multiple in vitro strategies for cholesterol-lowering, including cell-surface adsorption (heat-inactivated cells), bile-enhanced removal (oxgall effect), and enzymatic transformation, with the gene RS03310 implicated as the main contributor. These findings provide in vitro mechanistic insights into Blautia-mediated cholesterol metabolism, highlight RS03310 as a candidate gene associated with cholesterol biotransformation, and advance our understanding of the potential role of Blautia in host cholesterol homeostasis.

overall_design: RNA-seq profiling of B. hominis HA2291 cells after 48h growth (OD600=0.8) in mGAM media supplemented with (BHC)and without (BH) cholesterol (100µg/mL).

first: He

last: Jiang

first: Shuang-Jiang

last: Liu


title: Regulation of Sodium/Calcium Homeostasis by BacNav Gene Therapy Rescues Cardiac Dysfunction in Chronic Heart Failure

city: Durham

first: Nenad

last: Bursac

state: NC

address: 101 Science Drive

institute: Duke University

summary: Despite continued progress, therapies to augment contractile function and prevent arrhythmias in patients with heart disease remain limited. Here, we present a two-pronged gene therapy approach whereby simultaneous augmentation of peak Na+ current and Ca2+ transient amplitude in cardiomyocytes (CMs) effectively alleviates pathogenesis of heart failure. Specifically, using in vitro engineered tissue models of neonatal rat CMs, ex vivo adult mouse CMs, and in silico rabbit CMs, we show that expression of prokaryotic Na+ channels (BacNav) dose-dependently enhances Ca2+ transient amplitude and contractility of CMs by modulating the activity of the Na+/Ca2+ exchanger and increasing sarcoplasmic reticulum Ca2+ stores. In vivo, AAV9-mediated BacNav therapy rescues contractile deficit and prevents arrhythmias in a pressure-overload induced model of chronic heart failure in mice. BacNav therapy also confers protective effects on pressure-overload induced dysregulation of the cardiac transcriptome. We further establish the safety of long-term systemic delivery of AAV9-BacNav in mice. Collectively, these studies support the translational promise of BacNav gene delivery as a novel therapy for electrical and contractile dysfunction in heart failure.

overall_design: Bulk RNA-sequencing from C57Bl/6J mouse ventricular tissues to assess BacNav gene therapy in a murine transverse aortic constriction model. Three groups were included: 1) Sham mice injected with PBS 2) TAC mice injected with AAV9-MHCK7-mScarlet 3) TAC mice injected with AAV9-MHCK7-BacNav-mScarlet

first: Tianyu

last: Wu

first: Yongwu

last: Li

first: Robin

middle: M

last: Perelli

first: Yiu Yan

last: Siu

first: Anna

last: Tornatore

first: Josue

last: Nataren

first: Xixian

first: Sophia

last: Deluca

first: Donald

last: Bers

first: Craig

last: Henriquez

first: Andrew

middle: P

last: Landstrom


title: Myosin VB is Critical for Progenitor Cell Function in the intestine

city: Nashville

first: Izumi

last: Kaji

state: TN

address: Rm 10465H, MRB IV

department: Surgery

institute: Vanderbilt University Medical Center

summary: Microvillus inclusion disease (MVID) is a congenital diarrheal disorder, caused by inactivating mutations in myosin Vb (MYO5B). MYO5B deficient mice and cell lines have demonstrated the importance of MYO5B in enterocyte brush border development; however, the previous MYO5B knockout models lacked specificity to the stem cell function. To address the direct impact of MYO5B loss on the epithelial stemness, we investigated the effects of progressive MYO5B deficiency originating in mouse intestinal crypt cells. Our transcriptomic and multi-plex immunostaining datasets demonstrate that MYO5B is critical for intestinal stem cell identity. MYO5B-deficient crypts acquire a hyperproliferative phenotype and lack the ability of proper cell lineage differentiation. An evident disruption in mitochondrial structure and fatty acid metabolism likely underlies these crypt deficits. Consistent with mouse models, MVID patient biopsies demonstrate abnormal expansion of proliferative zone besides villus blunting. These data reveal the direct impacts of MYO5B loss on intestinal epithelial cell progenitor functions.

overall_design: Jejunal epithelial cells and lamina proprial cells were isolated from the mice of crypt-specific MYO5B knockout (Day 3 Lrig1-M5B), crypt-specific MYO5B mutation (Day 3 Lrig1-G519R), whole epithelial MYO5B knockout (Day 5 Lrig1-M5B), whole epithelial MYO5B mutant (Day 5 Lrig1-G519R), and littermate controls with intact MYO5B. Each group has two replicates.

first: Andreanna

last: Burman

first: Monica

last: Brown

first: Yilin

last: Yang

first: Ken

middle: S

last: Lau

first: Michael

last: Momoh


title: Bacteroides intestinalis–Driven Arabinoxylan Fermentation Mitigates Inflammatory and Metabolic Dysfunction

city: Champaign

first: Wenyan

last: Mei

state: IL

address: 2001 S Lincoln Ave, VMBSB3411

institute: University of Illinois at Urbana-Champaign

summary: Insufficient dietary fiber intake is strongly associated with gut microbiome dysfunction and an increased risk of noncommunicable diseases. Synergistic synbiotics, which pair defined microbial strains with their preferred carbohydrate substrates, offer a promising strategy to restore these functions. However, the rational design of such interventions remains challenging by insufficient understanding of microbial fiber-degrading capacities and the host-relevant bioactivities of fermentation-derived metabolites. Here, we identify human colonic commensal Bacteroides intestinalis (B. intestinalis) as a key microbial mediator of dietary fiber-driven metabolic, immune, and neuronal benefits. We demonstrate that the synergistic interaction between B. intestinalis and its preferred substrate, insoluble wheat arabinoxylan abundant in dietary fiber, enhances the production of anti-inflammatory, antioxidant, and anti-diabetic phenolic compounds and bile acid species. These metabolic effects are accompanied by coordinated transcriptional remodeling in the colon and spleen that improve circadian rhythm regulation, lipid metabolism, and immune defense. Importantly, these beneficial effects are preserved in conventionally raised mice with established high fat diet-induced obesity, where BI and inWAX improves glucose tolerance along with an increased production of neuroactive compounds. Our findings uncover a mechanistic framework linking B. intestinalis-mediated fiber fermentation to gut–liver–brain crosstalk and establish a rational foundation for precision synbiotic design.

overall_design: RNA-seq profiling DSS_cellulose_Spleen, DSS_InWax_Spleen, Water_cellulose_DC, Water_InWax_DC, DSS_cellulose_MC, and DSS_InWax_MC


title: Distinct phenotypes and repertoires of bronchoalveolar and airway mucosal T cells in health and allergic asthma

city: Charlestown

first: Neal

middle: Patrick

last: Smith

address: 149 13th Street

institute: Massachusetts General Hospital

summary: T cells play a central role in host protection against respiratory pathogens, but a maladaptive T cell response can lead to pulmonary diseases. Defining the biology of protective versus pathogenic T cell responses in the lungs of humans will be critical to nominate novel approaches to improve respiratory health. Previous studies have examined T cells from the lungs captured via bronchoalveolar lavage (BAL), endobronchial brushings, or biopsies. However, whether these different approaches are capturing distinct T cell phenotypes and/or clonotypes remains unclear. We aimed to evaluate and compare the transcriptional signatures of T cells isolated via BAL versus endobronchial brushings in healthy controls (HCs) and allergic asthmatics (AAs). The most significant difference in T cell subsets abundance between AAs and HCs was the enrichment of CD4 T helper type 2 (Th2) cells when comparing endobronchial brush samples (OR=26.2, P=0.002), but not when examining BAL (OR=1.7, P=0.46), indicating differences in the T cell subsets captured from the BAL versus airway mucosa specimen processing. TCR repertoire analysis revealed that brush T cells contained dramatically expanded TCR clones. Expanded T cell clones from the brush expressed high levels of resident-memory markers, suggesting the airway mucosa is enriched for TRM cells with unique TCR specificity.

overall_design:
Flexible bronchoscopy was performed to obtain BAL and endobronchial brushings from 3 HC and 3 AA subjects. CD3+ T cells were sorted and single cell RNA- and T cell receptor (TCR)-sequencing was performed using the 10X Chromium platform. Unbiased clustering, differential gene expression analysis and TCR repertoire analysis was performed.

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Raw files will be uploaded to dbGaP due to patient privacy concerns.
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first: Rod

last: Rahimi

middle: D

last: Luster

first: Alexandra-Chloe

last: Villani


title: Spatial transcriptomic profiling reveals body site-specific inflammatory differences in psoriasis lesions

city: Aarhus

first: Morten

middle: Muhlig

last: Nielsen

address: Palle Juul-Jensens Bouleward 99

department: Department of Molecular Medicine

country: Denmark

institute: Aarhus University

summary: Psoriasis is a common chronic inflammatory skin disease. Treatments lead to substantial improvement of most psoriasis plaques. However, it can be challenging to reach disease resolution in certain hard to treat areas such as scalp, and lower extremity. Here we map histologic and spatial transcriptomic differences between psoriasis lesions across different anatomical locations, to understand if differences can be linked to plaque-site specific treatment resistance. Quantitative immunohistochemical analysis and transcriptomic digital spatial profiling were performed on skin punch biopsies obtained from unaffected areas on the trunk, lesional (LS) areas of the scalp, upper extremity and lower extremity of 12 patients with psoriasis. Histological analysis showed no significant differences in epidermal thickness among LS skin from different body locations. Immunohistochemical markers (CD3, CD4, CD8, CD103, CD207, IL-12RB1, IL-17A, IL-23R, RORγt, FOXP3, and MPO) did not differ significantly between LS sites. Whole transcriptome spatial RNA profiling identified several differentially expressed genes that revealed site-specific transcriptomic differences. Notably, IL-23 signaling was significantly enriched in the lower extremity epidermis, and IL-17 signaling was more pronounced in the epidermis of LS samples. These findings highlight minimal histological and immunohistochemical variation, yet significant transcriptomic and pathway differences between psoriasis body locations, suggesting potential targets for site-specific therapeutic strategies.

first: Thomas

last: Emmanuel

first: Hakim

last: Abdallah

first: Claus

last: Johansen


city: Chicago

first: Weiguo

last: Cui

address: 303 E Chicago Ave

department: Pathology

institute: Northwestern University

overall_design: KLF2 CUT&Tag assay on P14 cells isolated from naïve mice or LCMV Armstrong infected mice on day 8 post-infection.

first: Kexin

last: Gai


title: Single-nucleus RNA sequencing of colon tissue from Pink1 knockout and wild-type mice

status: Public on Mar 09 2026

city: Suwon

first: Eun

middle: Jeong

last: Lee

state: Gyeonggi-do

address: 206 World cup-ro, Yeongtong-gu

department: Department of Brain Science

country: South Korea

institute: Ajou University

summary: Mutations in PTEN-induced kinase 1 (Pink1), have been associated to mitochondrial dysfunction and gastrointestinal abnormalities. We generated single-nucleus RNA sequencing (snRNA-seq) profiles from colon tissues of wild-type (WT) and Pink1 knockout (KO) mice to characterize cell-type specific transcriptional changes associated with loss of Pink1.

overall_design: Colon tissue was collected from 15-week-old male Pink1 knockout (KO) mice (C57BL/6) and age and sex-matched wild-type (WT) littermates as controls. The colon was detached from the mesenteric tissues, and nuclei were isolated by detergent-based lysis. Sorted nuclei were pooled and loaded onto 10x Genomics Chromium single-cell 3′ library preparation followed by Illumina sequencing. Obtained raw reads were processed with standard snRNA-seq pipline to generate the gene and barcode UMI count metrics.

first: Muhammad

last: Junaid

first: Soo Jung

last: Park

first: Yiseul

last: Bae

first: Eun Jeong

first: Su Bin

last: Lim


title: Single-cell RNA sequencing of bone marrow celld from patients with paroxysmal nocturnal hemoglobinuria.

city: Bethesda

first: Shouguo

last: Gao

state: MD

address: 9000 Rockville Pike

department: NHLBI

institute: National Institutes of Health

summary: We performed single cell RNA sequencing of bone marrow samples (sorted Lineage+ cells, and sorted Lin-CD34+ HSPCs) from 8 patients with paroxysmal nocturnal hemoglobinuria (PNH) to understand PNH pathophysiology at high multi-dimensional resolution.

overall_design: RNA profiles of single bone marrow hematopoietic cells of 8 PNH patients and 5 healthy donors were generated by deep sequencing using Illumina NovaSeq.

first: Hiroki

last: Mizumaki


title: Silencing of PARN in NCI-H520 cells induces changes in the miRNome

city: Trento

first: Michela

middle: A.

last: Denti

address: Via Sommarive 9

department: Department of Cellular, Computational and Integrative Biology

country: Italy

institute: University of Trento

summary: To understand the role of PARN  we have employed miRNAs microarray expression profiling as a discovery platform to identify miRNAs whose expression is regulated by PARN

overall_design: NCI-H520 cells were silenced with shRNAs against PARN or control shRNAs, in six replicas, as previously described (Maragozidis, P., Papanastasi, E., Scutelnic, D., Totomi, A., Kokkori, I., Zarogiannis, S.G., Kerenidi, T., Gourgoulianis, K.I., and Balatsos, N.A. (2015). Poly(A)-specific ribonuclease and Nocturnin in squamous cell lung cancer: prognostic value and impact on gene expression. Mol Cancer 14, 187. PMID: 26541675).  RNA was collected 72 hours after transfection and knock-down of PARN mRNA was validated by RT-PCR on each independent replicate sample.

first: Nikolaos

last: Balatsos


title: CD47 promotes MAPK and epithelial-to-mesenchymal transition molecular programs to drive pro-metastatic phenotypes in non-small cell lung cancer

city: Toronto

first: Kelsie

last: Thu

state: ON

address: 209 Victoria Street

country: Canada

institute: Keenan Research Centre for Biomedical Science

summary: CD47 is best known for its role in tumor immune evasion; however, studies in diverse cell models indicate that it also has cell-autonomous, tumor-promoting functions which are cell type- and context-specific. Motivated by the prognostic and therapeutic significance of CD47 and the limited knowledge regarding its roles beyond immune evasion in non-small cell lung cancer (NSCLC), we sought to define the cellular and molecular processes driven by intrinsic CD47 signaling in NSCLC. Transcriptome profiling of CD47 wildtype and knockout NSCLC cells implicated its regulation of genes enriched for signatures of MAPK signaling and epithelial-to-mesenchymal transition (EMT). A significant positive association between CD47 and MAPK/EMT expression signatures was also evident in large cohorts of NSCLC cell lines and tumor tissues. Functional studies indicated that CD47 does not regulate cell proliferation in NSCLC cells like it does in other cancer types. Instead, CD47 regulates cell adhesion and migration through an ERK and EMT axis, validating our transcriptomic findings. Moreover, CD47 loss-of-function significantly diminished the ability of NSCLC cells to metastasize in vivo, demonstrating the physiological relevance of cell-intrinsic CD47 signaling in lung cancer cells. Our data reveal a novel role for CD47 in relaying signals through ERK to promote EMT expression programs and pro-metastatic phenotypes in NSCLC. Although additional mechanistic studies are needed to further decipher the CD47-ERK-EMT signaling pathway, our findings reinforce the therapeutic potential of CD47, rationalizing further research to develop CD47 blockade as a multimodal therapy for NSCLC.

overall_design: RNA-seq profiling of clonal wild-type and CRISPR-mediated CD47 knockout Lewis Lung Carcinoma cells (LLC) collected in vitro.

first: Asa

last: Lau

first: Lilian

last: G Zhai

first: Ryunosuke

last: Hoshi

first: Zackary

last: Rousseau

first: Abraam

last: Zakhary

first: Yin Fang

last: Wu

first: Rola

last: Saleeb

first: Heyu

last: Ni


title: Integrated metabolome and transcriptome profiling demonstrates dynamic regulatory roles of hormones in direct-seeding rice

status: Public on Mar 06 2026

city: Shanghai

first: Yang

last: Hang

address: 1000 Jinqi Road, Fengxian District

institute: Shanghai Academy of Agricultural Sciences

summary: Direct-seeding rice faces the prominent challenge of low seedling emergence vigor, particularly under deep-sowing mechanical resistance and hypoxic conditions. Although some physiological traits are known, the systemic molecular networks determining superior emergence remain elusive. Here, we integrated metabolomic and transcriptomic analyses to compare the elite direct-seeding variety ChongShang2022 (CS2022) with the control Huxiangruan450 (HXR450). Weighted gene co-expression network analysis (WGCNA) identified germination-associated metabolic modules. Hub metabolite analysis revealed that the accelerated germination of CS2022 correlates with a higher accumulation of cytokinins (zeatin and cis-zeatin-9-N-glucoside), known for antagonizing abscisic acid (ABA)-induced dormancy, alongside key amino acids (e.g., L-lysine) and structural sphingolipids. Physiological validation confirmed the functional significance of these hubs, demonstrating that exogenous trans-zeatin and L-lysine significantly promoted seed germination in a dose-dependent manner. Notably, CS2022 exhibited heightened sensitivity, achieving maximal promotion at concentrations approximately 10-fold lower than HXR450. Targeted LC-MS/MS assays further demonstrated that CS2022 maintains a significantly higher GA20/ABA ratio during germination by accumulating the key precursor GA20 and deactivating free ABA into ABA-glucosyl ester. This hormonal homeostasis couples with elevated α-amylase activity, accelerating energy mobilization. At the seedling stage, multi-omics integration suggests an optimized growth-defense trade-off in CS2022. Auxin signaling supports rapid elongation, while the upregulation of jasmonic acid (JA) precursor transcripts contrasts with restricted accumulation of bioactive signals (e.g., JA-Ile). This potential signal buffering mechanism likely mitigates growth arrest. Additionally, lipid remodeling involving sphingolipids and waxes may contribute to hypoxia tolerance. Altogether, this study delineates a correlative regulatory network where dynamic hormone buffering, redirected metabolic flux, and adaptive lipid remodeling synergistically maximize direct-seeding rice emergence vigor, providing mechanistic insights and candidate modules for breeding.

overall_design: We performed transcriptome sequencing on 5 days after sowing seedlings following direct seeding of both varieties and conducted a multi-omics integrated analysis.

first: Hang

last: Yang

first: Zejun

last: Hu

first: Ying

last: Yan


title: CCAAT‐enhancer binding protein delta functions as a tumor suppressor gene in acute myeloid leukemia

status: Public on Mar 07 2026

city: Charlottesville

first: Subhash

last: Prajapati

address: 1340 Jefferson Park Avenue

department: Biochemistry and Molecular Genetics

institute: University of Virginia

summary: There is a continued need for identification of novel disease drivers of acute myeloid leukemia (AML) as many patients experience relapse and have poor clinical outcomes. Using genomic analyses of a study dataset of paired diagnosis and relapse specimens (n = 59), we identified recurrent downregulation of CCAAT-enhancer binding protein delta (CEBPD) expression at relapse and inferred CEBPD as one of the key regulators of gene transcription in a subset of relapse patients. Three independent public datasets validated downregulation of CEBPD expression at relapse and predicted it as a candidate tumor suppressor gene in AML. To evaluate CEBPD’s tumor suppressor function, we performed complementary loss- and gain-of-function experiments in human AML cell lines OCI-AML2 and OCI-AML5. Consistent with the prediction, knockdown of CEBPD expression led to activation of MAPK signaling and upregulation of downstream effectors cyclin D1 and TNFα expression with concomitant increase in leukemic growth, while CEBPD overexpression resulted in induction of myeloid differentiation marker CD14 expression in the cell lines. Consistent with prior reports, our integrative genomic analyses and azacytidine treatment experiments further suggest a role for DNA methylation in downregulation of CEBPD expression during AML progression. Collectively, our results provide direct functional evidence for a tumor suppressor function of CEBPD in human cell lines and support prior studies implicating its epigenetic silencing in human AML.

overall_design: RNA-Seq of CRISPR-mediated CEBPD knockdown and control OCI-AML5 samples

first: Francine

last: Garrett-Bakelman


title: Fibro-Adipogenic Progenitor cells from murine SMA muscles are intrinsically adipogenic

status: Public on Mar 05 2026

city: Gainesville

first: Yangyi

middle: Edward

last: Luo

state: FL

address: 1864 Stadium Road

institute: University of Florida

summary: Spinal muscular atrophy is a neurodegenerative disorder caused by mutations in the SMN1 gene. Although classically viewed as a neurogenic disease, SMA patients exhibit poor skeletal muscle regeneration and increased fatty-fibrotic infiltration. Fibro-Adipogenic progenitors are mesenchymal precursor cells that contribute to muscle remodeling and underly fat and fibrosis formation. Because FAPs transiently express Smn1 during regeneration, FAPs were examined in muscles from adult  SMA and control mice to determine if reduced Smn activity altered their properties. We performed a non-biased screen of FAPs following BaCl2-induced injury using an in-situ cell surface proteomic strategy that probed the cellular membrane and environment of FAPs in early regeneration. Proteomic profiling revealed early adipogenic priming in SMA tissues, with increased levels of perilipin-4 and adipocyte lipid-binding proteins. Significantly more adipocytes accumulated in  SMA muscles after glycerol injection versus controls. Further, SMA FAPs produced more fat than control FAPs when transplanted into glycerol injured muscles lacking FAPs. RNA sequencing of FAPs isolated after BaCl2 or glycerol injury identified transcriptional enrichment of lipid biosynthesis and dysregulated lipid metabolism in SMA FAPs. Primary FAPs isolated from SMA muscles mirrored heightened adipocyte formation, which was normalized by increasing Smn activity with Risdiplam. Conversely, adipogenesis of primary FAPs from control muscles was enhanced when subjected to siRNA Smn1 knockdown. Together, these findings demonstrate that reduced Smn activity potentiates intrinsic adipogenic bias in FAPs that may contribute to pathological fat deposition in SMA muscle.

overall_design: Primary FAPs isolated using MACS at 3dpi after either BaCl2 or Glycerol injury

first: Yangyi E.

first: Elisabeth R.

last: Barton


title: Macrophage activation and invasion by Porphyromonas gingivalis is modulated by PPAD and accessory fimbriae subunits

city: Louisville

first: Jan

last: Potempa

state: Kentucky

address: ULSD, 501 S. Preston St.

institute: University of Louisville

summary: Background: Porphyromonas gingivalis is a master manipulator of host immune responses in periodontium. Peptidyl arginine deiminase (PPAD), a recently described virulence factor of P. gingivalis, responsible for both host- and bacterium-derived proteins and peptides citrullination,  also plays an important role in hijacking immune responses. While PPAD’s modification of fimbrial subunits (FimCDE) affects TLR2 signaling in fibroblasts, its impact on immune cells remains unclear. Methods: Human monocyte-derived macrophages (MDMs) were stimulated with wild-type or mutant P. gingivalis strains and isolated fimbriae. Inflammatory responses were assessed by measuring cytokine expression and secretion, transcriptional changes using RNA-seq and Pi3K/Akt pathway activation, while bacterial invasion through flow cytometry, fluorescent  microscopy and intracellular survival assay. Results: PPAD-modified fimbriae enhanced MDM proinflammatory responses, such as PGE2- related gene expression as well as cytokines secretion, while fimbriae from accessory subunit mutants failed to induce inflammation. PPAD modification of accessory fimbrial subunits was found to protect P. gingivalis from killing by macrophages. PPAD and accessory fimbriae subunits were involved in complex immune evasion strategies, upregulating genes associated with viral infections or interactions with T cells. Conclusions: These findings highlight the importance of protein citrullination in TLR2-dependent signaling and provide insight on how P. gingivalis subverts host immune responses.

overall_design: Comparative gene expression profiling analysis of RNA-seq data for MDMs that  were infected with  various strains of P. gingivalis ( ATCC 33277 WT and  ATCC 33277-derived mutants of PPAD, FimA, FimC and FimE as well as W83 WT strain) at MOI 20 for 24 h.

first: Aleksandra

last: Wielento

first: Dominika

last: Drapała

first: Marina

last: Terekhova

first: Anna

last: Jacuła

first: Maxim

middle: N

last: Artyomov

first: Jakub

last: Kochan

first: Yoshiaki

last: Hasegawa

first: Danuta

last: Mizgalska

first: Juhi

last: Bagaitkar

first: Aleksander

last: Grabiec


title: Defining the chromatin-associated protein landscapes on Trypanosoma brucei repetitive elements using synthetic TALE proteins

city: Edinburgh

first: Robin

last: Allshire

address: Max Born Crescent,

country: United Kingdom

institute: Edinburgh university

summary: Kinetoplastids, such as Trypansoma brucei, are eukaryotes that likely separated from the main lineage at an exceptionally early point in evolution. Consequently, many aspects of kinetoplastid biology differ significantly from other eukaryotic model systems, including yeasts, plants, worms, flies and mammals. As in many eukaryotes the T. brucei genome contains repetitive elements at various chromosomal locations including centromere- and telomereassociated repeats and interspersed retrotransposon elements. T. brucei also contains intermediate-sized and mini- chromosomes that harbor abundant 177 bp repeat arrays, and 70 bp repeat elements implicated in Variable Surface Glycoprotein (VSG) gene switching. In many eukaryotes repetitive elements are assembled in specialised chromatin such as heterochromatin, however, apart from centromere- and telomere-associated repeats, little is known about chromatin-associated proteins that decorate these and other repetitive elements in kinetoplastids. Here we utilize affinity selection of synthetic TALE DNA binding proteins designed to target specific repeat elements to identify enriched proteins by proteomics. Validating the approach, a telomere repeat binding TelR-TALE identifies many proteins previously implicated in telomere function. Furthermore, the 70R-TALE designed to bind 70 bp repeats indicates that proteins involved in DNA repair are enriched on these elements that reside adjacent to VSG genes. Interestingly, the 177 bp repeat binding 177R-TALE enriches for many kinetochore proteins suggesting that intermediate-sized and mini- chromosomes assemble kinetochores related in composition to those located on the main megabase chromosomes. This provides a first insight into the chromatin landscape of repetitive regions of the trypanosome genome with relevance for their mechanisms of chromosome integrity, immune evasion and cell replication.

first: Roberta

last: Carloni

first: Tadhg

last: Devlin

first: Pin

last: Tong

first: Tania

last: Auchynnikava

first: Christos

middle: R

last: Spanos

first: Juri

last: Rappsilber

first: Keith

last: Matthews


title: Inflammatory arthritis immune related adverse events represent a unique autoimmune disease entity primarily driven by T cells, but likely not autoantibodies

city: Rochester

first: Hu

last: Zeng

state: MN

address: 209 Third Ave SW

department: Rheumatology

institute: Mayo Clinic

summary: Immune checkpoint inhibitor (ICI)-induced inflammatory arthritis (IA) is an increasingly recognized immune-related adverse event (irAE), yet its underlying immunopathogenesis remains poorly understood. Unlike rheumatoid arthritis (RA), where autoantibodies and B cell dysfunction are central features, the contribution of humoral immunity to IA irAE is unclear. Here, we performed in-depth immunophenotyping of peripheral blood from patients with IA irAE, and compared them with seronegative RA patients, ICI-treated patients without irAE, and healthy controls. IA irAE was marked by a distinct T cell-dominated profile, with CD4+ T cells exhibiting reduced CXCR3 and CCR6 expression, and both CD4+ and CD8+ T cells showing increased cytotoxic molecule expression and metabolic activation. In contrast to seronegative RA, IA irAE patients displayed no significant elevation in autoantibody levels or atypical CD11c+CD21- B cells. IA irAE was further characterized by a proinflammatory cytokine milieu, with elevated levels of IL-6, IL-12, and type I IFN, which correlated with the observed T cell activation phenotypes. Altogether, our findings define IA irAE as an immunologically distinct entity from RA, representing a naturally occurring model of antibody-independent systemic autoimmunity in humans. These results suggest that pathogenic T cell responses, potentiated by specific inflammatory cytokines, may be sufficient to drive arthritis in the absence of humoral autoimmunity, offering new insights into immune tolerance breakdown and therapeutic targeting in irAEs.

overall_design: 4 groups of patients were recruited for this study, IA irAE (irAE) patients are cancer patients on PD-1 or PD-L1 inhibitors (pembrolizumab, nivolumab, cemiplimab, atezolimumab, durvalumab, or avelumab) therapy without pre-existing rheumatic diseases, who develop physician confirmed inflammatory arthritis; ICI-control (ICI) patients are cancer patients on PD-1 or PD-L1 inhibitors therapy without pre-existing rheumatic diseases, who have not developed any irAE; RA-control (RAC) patients are non-cancer patients with rheumatoid arthritis that match those with de novo rheumatic irAE; and heathy control (HC) are the sex- and age-matched healthy individuals.

first: Xingxing

last: Zhu

first: Yue

last: Yu

first: Yanfeng

last: Li

first: Panwen

last: Wang

first: Ying

first: Chantal

last: McCabe

first: Shiju

last: Chen

first: Hannah

last: E. Langenfeld

first: Andrew

last: C Hanson

first: Brenna

last: E. Sharp

first: Amber

last: Woltzen

first: Cynthia

last: S. Crowson

first: Svetomir

last: N. Markovic

first: John

last: M. Davis III

first: Haidong

last: Dong

first: Uma

last: Thanarajasingam


title: Evolutionary expansion of the corticospinal system is linked to dexterity in Peromyscus mice

city: Cambridge, MA

first: KT

last: Tyssowski

state: Massachusetts

address: 16 Divinity Ave

institute: Harvard University

summary: While the central nervous system is perpetually reshaped by evolution, the principles governing how such changes promote ecologically relevant behaviors without breaking established functions are poorly understood. The expansion of neuron number is a potential mechanism by which the nervous system evolves to support changes in behavior without disrupting existing circuit function. Corticospinal neurons (CSNs) are a classic example: an expansion in the corticospinal system in the primate lineage has been hypothesized to underlie their exceptional dexterity. However, the role of CSN number in behavior has been difficult to assess due to the lack of a tractable model system. We compared two closely related subspecies of deer mice (Peromyscus maniculatus): forest mice, which evolved the ability to adeptly climb, presumably to support a semi-arboreal lifestyle, and prairie mice, which are less proficient climbers. We find that forest mice have about two-fold larger corticospinal tracts (CSTs) driven by an increase in CSN number in secondary motor and sensory cortical areas (M2 and S2). Furthermore, forest mice display greater manual dexterity than their prairie counterparts in a reach-to-grasp task, consistent with the idea that an increase in CSN number supports more dexterous behavior. High-throughput neural recordings during this task revealed a difference in the timing of neural activity between forest and prairie mice, specifically in M2: in forest mice, the peak of activity was shifted towards the grasping phase of the behavior. Forest mice also outperform their prairie counterparts on an ecologically relevant climbing task, where they spend more time upright crossing a thin rod, move faster, and right themselves more quickly when they fall, suggesting a general difference in motor dexterity not restricted to hand use. Finally, we use F2 hybrid animals to show that CST size is correlated with climbing dexterity, providing support for the long-standing hypothesis that corticospinal system expansion supports the evolution of dexterity. Together, our work establishes the forest-prairie deer mouse system as a model to investigate the role of neuron number expansion, and CSNs in particular, in dexterous movement.

sample_organism:
Peromyscus maniculatus bairdii
Peromyscus maniculatus nubiterrae

overall_design: We used the frontal cortex of five animals of each subspecies (P.maniculatus bairdii, BW; P.maniculatus nubitarrae, NB). The anterior half of the cortex was extracted from both hemispheres for each animal (this includes all of sensorimotor cortex, as well as other areas) and flash-frozen in liquid nitrogen.

first: Kelsey


title: Rectal RNA-seq of mice treated with a multistrain Lactobacillus/Bifidobacterium-derived postbiotic (IBM)

city: Akabanedai

first: Takumi

last: Iwasawa

state: KIta

department: Institute of Life Innovation Studies

country: Japan

institute: Toyo University

summary: This dataset provides rectal transcriptomic profiles of mice after 7-day oral IBM administration, enabling pathway-level analyses of epithelial and mucosal responses to a multistrain postbiotic preparation.

overall_design: Male C57BL/6NJ mice (8 weeks old) were randomly assigned to receive oral IBM or vehicle twice daily for 7 consecutive days. IBM is a cell-free fermented soybean extract produced by co-culturing 31 Lactobacillus/Bifidobacterium-related strains. At day 7, rectal tissues were collected and total RNA was extracted for bulk RNA sequencing. The primary objective of this experiment was to identify DSS-independent transcriptional programs associated with IBM administration, with emphasis on epithelial barrier- and circadian-related pathways.


title: BLIMP1 shapes germinal center B-cell clonal diversity by gating chromatin accessibility during light-to-dark zone transition

city: Pittsburgh

first: Harinder

last: Singh

address: 5051 Centre Avenue

department: Center for Systems Immunology and Department of Immunology

institute: University of Pittsburgh

summary:
Extensive studies have delineated signaling systems and transcription factors (TFs) that positively regulate GC B cell responses. In the LZ, T follicular helper (Tfh) derived CD40L and ICOS along with B cell receptor (BCR) signals license B cell clones to pass through the G1-S checkpoint; the cells then re-enter the DZ for clonal expansion and AID mediated somatic hypermutation (SHM). Among TFs that promote GC initiation, selection, and output, BCL6 programs GC identity. MYC licenses positively selected LZ cells for re-entry and proliferation in the DZ, whereas FOXO1 controls the program underlying rapid cell divisions. PU.1 and SPIB via interactions with IRF8 help maintain GC identity and selection, acting on ETS–IRF composite elements (EICE). BATF supports robust GC responses and class switching. The POU TF module comprised of OCT1/POU2F1, OCT2/POU2F2, and their co-activator OBF1/POU2AF1 maintains BCR-dependent transcription required for GC expansion. Canonical and alternative NF-κB components c-Rel and p52/RelB also promote GC maintenance. A p52–ETS1 complex has been recently shown to induce OCT1 and OBF1, thereby generating a feedforward regulatory loop.

In contrast, few signaling-induced negative regulators of the GC response that restrict clonal dominance have been identified, notably Nr4a1 (NUR77). We posited that BLIMP1 which promotes exit of GC B cells into the plasma cell (PC) pathway, could also act as a signaling-induced transient feedback gate to restrain the GC B cell response, thereby reducing clonal dominance. In keeping with this hypothesis, low and heterogenous expression of BLIMP1 has been reported in GC B cells and its loss has been shown to result in larger GCs. Furthermore, Conter et al. recently demonstrated using bone marrow chimeras that B-cell-intrinsic BLIMP1 loss results in more exuberant GC responses associated with enhanced proliferation of antigen-specific GC B cells. We note that in addition to the feedback gating model for BLIMP1 action in the GC considered by us, two other models could account for the GC phenotype: (i) increased GC seeding due to impaired plasmablast differentiation or (ii) failed GC exit due to blocked PC differentiation. We reasoned that integrated single cell (sc) transcriptional and chromatin analyses of GC B cells along with delineation of their clonal dynamics could distinguish among the three models. Furthermore, such high dimensional analyses of the perturbed and amplified GC response would yield insights into the underlying molecular mechanisms of BLIMP1 action.

Using sc transcriptome, V(D)J and chromatin profiling coupled with single nucleotide-resolution accessibility modeling of regulatory DNA sequences, we show that Prdm1-deficient B cells mount an exaggerated GC reaction characterized by larger clone sizes and enhanced affinity maturation culminating in greater clonal dominance. This phenotype is not attributable to increased GC seeding nor can it be merely accounted for by impaired exit of GC B cells into the PC pathway. Rather, the integrated genomic analyses reveal that BLIMP1 constrains expression of genes encoding components of the BCR-signaling cascade. Loss of this feedback, results in enhanced Syk, Lyn and Btk activity in GC B cells and augments chromatin engagement of signaling-inducible TFs at EICE, NF-κB and POU (OCT) motifs, promoting the G1–S transition during LZ selection and fueling DZ expansion.

overall_design: Eight to ten week old Prdm1fl/flCd19cre/+ (Prdm1 cKO) and Prdm1+/+ Cd19cre/+ (WT) mice were immunized intraperitoneally with 50 μg NP(23)-CGG (Biosearch Technologies) mixed with 50% (v/v) imject alum (Thermo Fisher Scientific) and 1 μg LPS (Sigma).

first: Godhev Kumar

last: Manakkat Vijay


title: M2 Macrophage-Derived Exosomes Ameliorate BPD by Inhibiting Ferroptosis via Suppression of the ZAKα-p38 Signaling Pathway

status: Public on Mar 04 2026

city: Wuxi

first: Yahui

last: Zhou

state: Jiangsu

address: No. 299-1 Qingyang Road, Liangxi District, Wuxi, Jiangsu, China

department: Department of Neonatology

institute: Affiliated Children’s Hospital of Jiangnan University

summary: Background: Bronchopulmonary dysplasia (BPD) is a common lung disease in premature infants. Hyperoxia-induced oxidative stress and ferroptosis are key pathological mech-anisms leading to alveolar epithelial (AT) cell injury and impaired alveolar development. M2 macrophage-derived exosomes (M2-Exo), as intercellular communication carriers, have potential protective effects in regulating oxidative stress-related diseases, but the molecular mechanism by which they exert effects by regulating ferroptosis in BPD re-mains unclear. Objective: To explore the protective effect of M2-Exo on hyperoxia or inflammation-induced BPD models and clarify its antioxidant mechanism. Method: In vitro AT cell injury models and in vivo BPD models were constructed by hyperoxia or LPS induction. M2-Exo were isolated, identified, and used to intervene in models. Oxidative stress and ferroptosis-related indicators (ROS, MDA, iron accumulation, GPX4), AT cell functional markers (AQP5, SPC), and ZAKα-p38 pathway activation contents were de-tected. ZAKα overexpression was used to verify pathway dependence. Results: M2-Exo intervention significantly enhanced AT cell viability, upregulated the expression of AQP5 and SPC, and reversed alveolar simplification. Concurrently, it effectively sup-pressed hyperoxia or LPS-induced oxidative stress and ferroptosis, as evidenced by re-duced contents of ROS and MDA, diminished iron accumulation, and GPX4 expression. Mechanistically, M2-Exo significantly inhibited the activation of the ZAKα-p38 pathway, and ZAKα overexpression could antagonize the antioxidant, anti-ferroptotic, and AT cell protective effects of M2-Exo. Conclusions: M2-Exo alleviate AT cell oxidative stress and ferroptosis by inhibiting the ZAKα-p38 pathway, thereby improving hyperoxia or in-flammation-induced BPD and providing a new strategy and molecular target for the antioxidant treatment of BPD.

overall_design: The experiment was carried out as follows: LPS-induced BPD model: Neonatal rats were randomly assigned to three groups: Con: Rats were raised in room air (21% O2) for seven days. LPS: Rats received daily intraperitoneal injections of LPS (500 μg/kg, 50 μL) under ambient air conditions. LPS + M2-Exo: Rats were treated with LPS (500 μg/kg) + M2-Exo (50 μg/kg) in a total volume of 50 μL daily. Hyperoxia-induced BPD model: Neonatal rats were randomly assigned to the following groups: Con: Rats were raised in room air (21% O2) for seven days. Hyperoxia (Hyp): Rats were exposed to 85% O2 in alternating cycles of 12 h hyperoxia and 12 h normoxia (21% O2). Hyp + M2-Exo: Rats received daily intra-peritoneal injections of M2-Exo (50 μg/kg, 50 μL) during exposure to hyperoxia. At the end of the experiment, rats were euthanized by cervical dislocation.

first: Yahan

last: Pu

first: Mingyue

last: Lv

first: Ru

last: Yan

first: Honglian

last: Zhang

first: Lihui

last: Yu

first: Weilai

last: Jin

first: Le

first: Zhiwei


title: Mettl8 programs Tcf1+CXCR5+ T cells in autoimmune disease and tumor by mediating Tcf1 mRNA m3C modification and Tcf1-bound chromatin loops

city: Houston

first: Jia

last: Li

state: Texas

address: 2121 W HOLCOMBE BLVD

department: CEDP

institute: Guangzhou Medical University

summary: In the tumor microenvironment (TME), the active tertiary lymphoid structure (TLS) plays a crucial role in fostering the reactivation of naïve or memory cells, leading to the expansion of effector cells. However, an excessive reinvigoration of T cells can result in autoimmune-like diseases, such as those observed in immune checkpoint blockade (ICB) therapy. Here, we have identified that the gene encoding RNA methyltransferase Mettl8 is highly expressed in inflammatory CD4+ CXCL13+ TFH cells of autoimmune patients. Surprisingly, the genetic deletion of Mettl8 in mice resulted in a reduced autoimmune phenotype in helper CD4 cells and slowed tumor growth through increased activation/effector response in CD8+ T cells. Mechanistically, Mettl8 is found to imprint m3C modification, stabilizing Tcf1 mRNA, and simultaneously interacts with Tcf1 protein to co-bind specific genome loops for genomic reorganization, as revealed by Hi-C analysis. These findings suggest that targeting Mettl8 promotes antitumor immunity while preventing the occurrence of autoimmune diseases. Notably, pharmacological inhibition of sumoylation-stabilizing Mettl8 protein has shown efficacy in compromising autoimmune CXCL13+ TFH specialization and function. In conclusion, these findings underscore the dual regulatory elements of the Mettl8-Tcf1 complex as a promising target for tumor immunotherapy, offering protection against autoimmune diseases.

overall_design: To investigate whether Mettl8 deficiency causes alterations in Tcf1 binding sites and chromatin accessiblity, we performed Mettl8 and Tcf1 CUT&Tag, and ATAC-seq in WT and Mettl8 KO CD8+ T cells.Given that Tcf1 regulates genomic organization to maintain CD8+ T cell identity, we next examined whether Mettl8 deficiency disrupts Tcf1-mediated 3D genome organization by HiC.To comprehensively understand the impact of Mettl8 deficiency on CD8+ T cells, we conducted RNA sequencing on sorted tumor-infiltrating CD8+ T cells. Considering the heterogeneous expression of these markers across T cell subsets, we further performed RNA sequencing on sorted Ly108+ Tim3− TPEX, Tim3+ CX3CR1+ Ly108− Int-TEX, and Tim3+ CX3CR1− Ly108− TEX subsets. To investigate the molecular mechanism of Mettl8 regulating TPEX cell transition, we conducted m3C-seq and Mettl8-RIP-seq using sorted tumor-infiltrating CD8+ T cells.


title: Synthetic lethality between RB-loss and E2F3 inhibition in small cell cancers targeted by pyrimidine synthesis blockade

city: Los Angeles

first: Evan

middle: Robert

last: Abt

state: CA

address: 650 Charles E. Young Drive, South

department: Molecular and Medical Pharmacology

institute: University of California Los Angeles

summary: Small cell carcinoma, often found with neuroendocrine features, is a lethal cancer variant, as seen for small cell lung cancer and treatment-resistant late-stage small cell neuroendocrine prostate cancer (SCPC). A genome-wide CRISPR dependency screen using SCPC models generated through human prostate cell transformation identifies a requirement for the transcription factor E2F3 in this cancer subtype. E2F3 dependency is linked to RB inactivation, an event that occurs nearly universally across small cell cancers. The requirement for E2F3 is shared by RB-deficient cells originating from the prostate, lung and adnexa (ovary and fallopian tube). In RB-deficient cancer cells, E2F3 inhibition restrains cell cycle progression, proliferation, and tumor growth in vivo. Inhibition of de novo pyrimidine synthesis limits E2F3 expression and suppresses small cell cancer proliferation in culture. Directly or indirectly targeting E2F3 to leverage a pan-cancer synthetic lethality resulting from RB inactivation represents a potential treatment strategy.

overall_design: Comparative sgRNA abundance profiling analysis of pooled CRISPR–Cas9 screening data in three PARCB cell lines transduced with the GeCKO sgRNA library, assessing sgRNA enrichment and depletion after 2 weeks of culture.

first: Owen

last: Witte

first: Thomas

middle: G

last: Graeber

first: Jack

last: Freeland

first: Liang

last: Wang


title: Dysregulated NK-cell gene expression defines the enduring symptoms of long COVID-19

city: Tubingen

first: Yogesh

address: Calwerstrasse 7

department: Institute of Medical Genetics and Applied Genomics

country: Germany

institute: Tubingen University

summary: Long-term COVID-19 syndrome (LTCS) or “long COVID” is a debilitating post-viral condition affecting approximately 2%–8% of individuals after SARS-CoV-2 infection. It manifests typically ≥3 months post-infection with symptoms persisting for at least 2 months, including fatigue, pulmonary dysfunction, and cognitive impairment, in the absence of alternative diagnoses. The biological mechanisms underlying LTCS remain poorly defined, yet emerging evidence implicates immune dysregulation.  We profiled plasma antibodies and cytokines from healthy controls (HC, N = 66), convalescents (CONV, N = 24), and LTCS patients (N = 94), followed by multiparametric 14-color flow cytometry of PBMCs from HC (N = 9), CONV (N = 6), and LTCS (N = 23) participants. To gain mechanistic insight, we performed single-cell transcriptomic profiling (scRNA-seq) on PBMCs from HC (N = 8), CONV (N = 6), and LTCS (N = 32) individuals. LTCS patients exhibited elevated anti-SARS-CoV-2 IgG (spike S1/RBD/N) titers compared to HC, but displayed significantly reduced systemic cytokine levels, including IFN-g, TNF-a, IL-6, and IL-10. Flow cytometry revealed marked depletion of CD56+CD16+ NK cells and CD56+CD3+ NKT cells, accompanied by altered T-cell activation states. scRNA-seq confirmed NK type I cell loss and uncovered broad transcriptional reprogramming with upregulation of PDCD4, CHD1, CXCR4, and SLC7A5 and downregulation of TGFBR3, RIPOR2, and MBNL1. Gene set enrichment analyses indicated activation of circadian and translational programs and suppression of olfactory receptor, neurotransmitter receptor, and GABA-gated ion-channel pathways. Functional assays validated reduced NK-cell inflammatory capacity in LTCS participants. LTCS is characterized by systemic cytokine attenuation and a quantitative and functional NK-cell deficit coupled to neurosensory pathway suppression. These findings identify NK cells as key sentinels of LTCS pathophysiology and highlight an NK-centric neuroimmune axis as a promising target for biomarker discovery and therapeutic intervention.

overall_design: The study design comprised a cross-sectional comparison of three participant groups: healthy controls with no history of SARS-CoV-2 infection or COVID-19 vaccination (HC; n=66), individuals who had recovered from mild–severe SARS-CoV-2 infection (convalescent, CONV; n=35), and participants with long-term COVID-19 syndrome (LTCS; n=114). Blood/PBMC samples were collected and profiled using complementary immune assays. Humoral immunity was assessed using a 3-plex SARS-CoV-2 antibody panel (HC n=66; CONV n=24; LTCS n=94), systemic inflammation was quantified using a 13-plex inflammation panel (HC n=66; CONV n=24; LTCS n=86), and cellular immune composition was characterized by 14-color immunophenotyping (HC n=9; CONV n=6; LTCS n=23). In a subset of participants, PBMCs were additionally analyzed by single-cell RNA sequencing using the Parse Biosciences Evercode combinatorial barcoding platform (HC n=8; CONV n=6; LTCS n=32) to resolve cell-type–specific transcriptional programs associated with convalescence and long-term COVID-19.

first: Urvi

last: Ray

first: Antje

last: Schulze Selting

first: Roshan

last: Priyarangana Perera

first: Zhiqi

last: Yang

first: Vladislav

last: Lysenkov

first: Siri

last: Göpel

first: Michael

last: Bitzer

first: Madhuri

last: Salker

first: Stephan

last: Ossowski

first: Olaf

last: Riess

first: Nicolas

last: Casadei


title: Connecting HTT intermediate alleles and microRNA dysregulation to enhanced tauopathy in Late-Onset Alzheimer's Disease

city: Oviedo

first: Sergio

middle: Pérez

last: Oliveira

state: Asturias

address: Avenida roma s/n

department: Investigación Clínica-Básica en Neurología

country: Spain

institute: Instituto de Investigación Sanitaria del Principado de Asturias (ISPA)

type: Non-coding RNA profiling by high throughput sequencing

summary:
Background: Late-onset Alzheimer´s disease (LOAD) is a heterogeneous disorder influenced by complex genetic factors. We previously described intermediate alleles (IAs; 27-35 CAG repeats) in the huntingtin (HTT) gene as potential modifiers in around 6% of AD population. The caudate nucleus, the most affected region in Huntington's disease, is highly sensitive to these HTT CAG repeats. We hypothesized that HTT IAs induce gene expression deregulation, including altered microRNA (miRNA) profiles, leading to altered disease progression.
Methods: We investigated the impact of HTT IAs on LOAD progression by genotyping HTT CAG repeats in a cohort of 323 LOAD patients and 335 healthy controls. Comprehensive histopathological and molecular analyses were performed on caudate nucleus samples from a matched subcohort (6 healthy controls, 14 LOAD non-HTT IA carriers, and 13 LOAD HTT IA carriers).
Results: HTT IAs carriers patients exhibited decreased survival after disease onset compared to non-carriers. Histopathologically, while LOAD patients showed increased soluble HTT levels and altered tau pathology compared to controls, these changes were consistently and markedly exacerbated in HTT IA carriers. This phenotype was characterized by heightened diffuse HTT immunoreactivity and an advanced maturation of tau pathology, specifically a pronounced increase in neuronal tau 3R burden and 3R tau-enriched ghost tangles. Interestingly, this pathological state was associated with alterations in key splicing factors, including decreased SRSF6 levels and increased nuclear FUS-SFPQ complex assembly. Analysis of microRNA (miRNA) profiling in the caudate nucleus revealed that the LOAD-associated miRNA dysregulation was significantly amplified in HTT IA carriers, identifying a signature of five miRNAs (miR-100-5p, miR-218-5p, miR-27b-3p, miR-487-3p, and miR-9-3p). In silico modeling and target validation demonstrated that these miRNAs target components of the nuclear spliceosome machinery, such as SRSF family, along with MAPT and HTT genes, suggesting a direct link to the observed tauopathy.
Conclusions: Our findings underscore that HTT IAs as critical modifiers in LOAD progression through an miRNA-mediated dysregulation of splicing and proteostasis. Thus, identifying HTT IAs through routine blood genetic screening offers a practical, non-invasive biomarker for patient stratification, taking a step forward to personalized therapeutic strategies in LOAD.

overall_design: miRNA-seq profiling of  33 human caudate tissue samples divided into three groups: 6 cognitively healthy controls, 14 LOAD patients without HTT intermediate alleles, and 13 LOAD patients with HTT intermediate alleles. The main variable is HTT genotype status within Alzheimer's disease. Control samples serve as a reference. No technical replicates are included.

last: Pérez-Oliveira

first: Juan

last: Castilla-Silgado

first: Paola

last: Pinto-Hernandez

first: Manuel

last: Fernandez-Sanjurjo

first: María Daniela

last: Corte-Torres

first: Olaya

last: Fernandez-Alvarez

first: Eduardo

last: Iglesias-Gutierrez

last: Menéndez-González

first: Cristina

last: Tomas-Zapico

first: Victoria

last: Álvarez


title: Gene expression microarrays of ONECUT2-overexpression in human pancratic islets

status: Public on Mar 03 2026

city: Malmö

first: Jones

middle: K

last: Ofori

address: Jan Waldenströms gata 35

department: Department of Clinical Sciences

country: Sweden

institute: Lund University

summary:
ONECUT2-overexpression impairs stimulus-secretion coupling in β-cells
To characterize the mechanisms underlying the dysfunction caused by ONECUT2-overexpression , we performed global transcriptomic analyses in human islets

overall_design: Total RNA was extracted from human islets after overexpression ONECUT2 in human islets (N=6 donors)

first: Ofori

last: Jones

first: Ling

last: Charlotte


title: Alu-mediated RNA duplexes are associated with widespread exon skipping across primate transcriptomes

city: Singapore

first: Yue

last: Wan

address: 60 Biopolis Street, Genome

country: Singapore

institute: Genome Institute of Singapore

summary: Alternative splicing patterns have diverged rapidly during vertebrate evolution, yet the mechanisms and functional consequences of species-dependent splice isoform differences are not well understood. Through an integrative analysis of genome-wide predictions of highly stable RNA duplexes, alternative splicing profiles, and proximity ligation-detection of RNA-RNA interactions in vivo, we observe evidence that the majority of long-range intronic RNA duplexes are mediated by inverted Alu-repeat elements, and that these structures are associated with widespread exon skipping in primates. Our results further reveal evidence that Alu-derived RNA duplexes have contributed to divergence in alternative splicing patterns during mammalian evolution.

overall_design: We applied SPLASH (Sequencing of Psoralen crosslinked, Ligated, and Selected Hybrids) to capture RNA secondary structures and RNA–RNA interactions in human nascent transcripts. Briefly, cultured human K562 cells were crosslinked in vivo at RNA base-paired regions. Following crosslinking, chromatin fractionation was performed to enrich chromatin-attached nascent RNA. Genomic DNA and ribosomal RNA were depleted to further enrich for the nascent RNA population. The crosslinked RNA base-paired regions were then biotin-labeled, and the RNA was fragmented before streptavidin affinity purification. The resulting double-stranded RNA molecules were proximity-ligated to form chimeric molecules, followed by reverse crosslinking. These molecules then underwent standard RNA-seq workflows, including reverse transcription, library preparation, and high-throughput sequencing.

first: Hyunbeen

last: Lee

first: Xinang

last: Cao

first: Guillermo

last: Parada

first: Ira

middle: A

last: Iosub

first: Jernej

last: Ule

first: Benjamin

middle: J

last: Blencowe


title: Centromeres are hotspots of DNA methylation epimutations that are transmitted and occur at high rates in a filamentous fungus

status: Public on Mar 02 2026

city: Colorado Springs

first: Andrew

middle: David

last: Klocko

state: Colorado

address: 278 Centennial Hall, 1420 Austin Bluffs Pkwy

department: Chemistry and Biochemistry

institute: University of Colorado Colorado Springs

summary: Epimutations are changes in chromatin modifications, such as DNA methylation or histone modifications. Some of these epigenetic changes can be inherited for several generations, and thus could contribute to evolutionary processes. Estimates of epimutation rates now exists in a few species, but epigenetic mechanism are not conserved across all life, and epigenetic marks funtion differently in different species. To understand the properties of epimutations in fungi, we performed a mutation accumulation experiment with the filamentous fungus Neurospora crassa and investigated spontaneous DNA methylation and trimethylation of lysine 9 on histone H3 (H3K9me3) changes in the mutation accumulation lines. We observed that centromeric regions are hotspots of spontaneous DNA methylation changes in N. crassa. In these hotspot regions, DNA methylation changes were transmitted across mitoses, but changes occurring in euchromatin were not maintained. The rate of DNA methylation changes was more than 10 000-fold faster than the genetic mutation rate. We did not observe spontaneous changes in H3K9me3 that were transmitted across mitoses. Our results show that while spontaneous epimutations occur in this species, they occur predominantly in gene poor heterochromatic regions, so their impact for evolutionary adaptation may be limited.

overall_design: Chromatin Immunoprecipitation-sequencing (ChIP-seq) of the trimethylation of lysine 9 on histone H3 (H3K9me3) of the filamentous fungus Neurospora crassa subject to a Mutant Accumulation experiment of single colony transfers followed by asexual growth

first: Mariana

last: Villalba de la Peña

first: Clayton

last: Hull-Crew

first: Taylor

last: Hutter

first: Cynthia

last: Vino

first: Peter

last: Sarkies

first: Maria

last: Colomé-Tatché

first: Frank

last: Johannes

first: Ilkka

last: Kronholm


title: Female iPSC X-chromosome inactivation (XCI) erosion and its transcriptomic effects during CRISPR gene editing and neural differentiation

city: Evanston

first: Christina

last: Thapa

state: Illinois

address: 1001 University Place

department: Center for Psychiatric Genetics (CPG)

institute: Endeavor Health

summary: Human induced pluripotent stem cells (hiPSC) and iPSC-differentiated neural cells, in combination with CRISPR editing, are commonly used for studying neurodevelopmental and other brain disorders. Female iPSCs undergo random X-chromosome inactivation (XCI) via epigenetic silencing by noncoding X inactive specific transcript (XIST). It is known that female iPSCs may lose XIST expression, leading to XCI erosion that affects both X-linked and autosomal gene expression. However, the effects of CRSIPR editing and neural differentiation on XCI erosion in iPSC-derived neurons and how this may confound a real-world transcriptomic analysis of differentially expressed genes (DEGs) are poorly understood. Here, leveraging bulk RNA-seq of hundreds of CRISPR-edited female iPSC lines from four donor lines for 66 genes and single-cell RNA-seq of iPSC-derived neurons of a subset of 42 edited genes, we investigated the effects of XCI erosion during CRISPR editing and in iPSC-derived neurons. We found that XCI erosion was variable in CRISPR-edited female iPSCs and largely preserved in iPSC-derived neurons. Like in iPSCs, XIST in neurons predominately influenced the expression of X-linked genes; however, its effect on autosomal genes was more pronounced in single neurons. Mechanistically, XIST epigenetically causes allelic imbalance of both X-linked and autosomal genes, with the former showing stronger allele-specific expression (ASE) bias. Notably, XIST-induced ASE bias exhibited a conserved positional pattern at loci affecting neurodevelopmental genes across different female lines and cell types. Finally, we demonstrated a confounding effect of XCI erosion on DEG analyses in iPSC-derived neurons. These results have significant implications in hiPSC modeling of neurodevelopmental and other brain disorders.

overall_design: As part of the SSPsyGene Consortium, our Assay and Data Generation Center (ADGC) for the Model of iPSC-derived Neurons for neurodevelopmental and psychiatric disorders (NPD) (MiNND) aims to generate isogenic hiPSC lines carrying (Loss-of-function) LoF alleles for about 150-200 NPD genes on multiple donor genetic backgrounds. Here, we generated 297 iPSC lines from 6 donor lines (4 females and 2 males) for 66 LoF genes across multiple batches. Transcriptional effect of LoF was assayed using bulk RNA-seq.

first: Jubao

last: Duan

first: Zhiping

last: Pang

first: Hanwen

last: Zhang


title: scRNAseq analysis of hepatic stellate cells in CCl4-induced liver fibrosis with eliminating p16high hepatocytes

city: Minato City, Tokyo

first: Teh-Wei

last: Wang

address: 4 Chome-6-1 Shirokanedai

institute: IMSUT

summary: Using scRNA-seq, we investigated the mechanism by which the removal of p16-high hepatocytes leads to the amelioration of CCl₄-induced liver fibrosis. Because liver fibrosis is primarily driven by hepatic stellate cells, we utilized a cell isolation protocol optimized for the efficient recovery of stellate cells.

overall_design: In this experiment, we obtained liver from p16-CreERT2/ Alb-DreERT2/ R26-CAG-LSL-RSR-tdTomato-2A-DTR (p16-Alb-LRTD) and p16-CreERT2/ R26-CAG-LSL-RSR-tdTomato-2A-DTR (p16-LRTD) mice following 4 weeks of CCl4, tamoxifen, and diphtheria toxin treatments. After perfusion, stellate cells were dissociated into single-cell suspensions using the pronase/ collagenase solution. Hepatic stellate cells were isolated by density gradient separation using Nycodenz solution and subsequent transcriptomic analysis.

first: Koji

last: Nishikawa

first: Makoto

last: Nakanishi


title: Shen-yuan-dan capsule inhibits METTL3-mediated m6A methylation to restore autophagy homeostasis and attenuate post-myocardial infarction heart failure

city: Beijing

first: Shuaijie

last: Guo

state: None Selected

address: 23 Art Museum Back Street, Dongcheng District, Beijing, China

institute: Beijing Hospital of Traditional Chinese Medicine

summary: Heart failure (HF) after myocardial infarction (MI) is a serious health issue. This study investigates the therapeutic effects of Shen-Yuan-Dan Capsule (SYD) on post-MI HF and explores its mechanisms, particularly involving m6A modification and autophagy. Using network pharmacology and MeRIP-seq, we identified potential epitranscriptomic targets. In vitro, H9c2 cardiomyocytes were treated with Phenylephrine (PE) and SYD. MeRIP-seq analysis identified differential m6A peak distribution among control, PE-induced, and SYD-treated groups, revealing that SYD alleviates HF by regulating the mTOR/TFEB autophagy pathway through inhibition of METTL3-mediated m6A modification.

overall_design: To investigate the m6A epitranscriptomic changes and identify potential targets of Shen-Yuan-Dan (SYD) capsule, we performed m6A Methylated RNA Immunoprecipitation Sequencing (MeRIP-seq). H9c2 cardiomyocytes were divided into three experimental groups: Control group (no intervention), Model group (induced with 50 µM Phenylephrine for 24 h to induce hypertrophy), and SYD group (treated with 1 mg/mL SYD and 50 µM Phenylephrine for 24 h). Total RNA was extracted, fragmented, and subjected to immunoprecipitation using an m6A-specific antibody. RNA libraries for both the immunoprecipitated (IP) and Input (total RNA) samples were constructed and sequenced.

first: Siqi

last: Chen

first: Changxu

last: Xie

first: Sinai

last: Li

first: Hongxu

last: Liu

first: Lei

first: Weihong

first: Mingxue

last: Zhou


title: Multi-tissue, multi-time-point transcriptomic atlas of aging in mice and rats [mouse]

city: Tarrytown

first: Kun

last: Xiong

state: NY

address: 777 Old Saw Mill River Road

department: Molecular Profiling and Data Science

institute: Regeneron Pharmaceuticals

summary: In order to get a greater understanding as to the genes and signaling pathways which are up- or down-regulated in a consistent manner throughout the rodent lifespan, we generated a high N age-related gene expression atlas in mice and rats, by profiling 28 tissues in male and female C57BL/6J mice, and 32 tissues in male Sprague Dawley rats (> 5000 samples) over multiple time points. We identified age-related genes and pathways that change either early in life, at mid-age, late in life, or linearly. Linear genes dominated many but not all tissues, and certain tissues (e.g. gut tissues) were relatively spared from age-related changes. We identified tissues that showed a strong sex bias or species bias. Given the expanse of our transcriptomic dataset, we hope this study will serve as a useful resource for understanding the timing, the tissue-specificity, the gender-specificity, and the species-specificity of age-related gene and pathway changes in male and female mice and male rats.

overall_design: Bulk RNAseq of 28 tissues of male and female mice at 6 age groups. Samples of diaphragm, soleus, gastrocnemius, and tibialis anterior were previously submitted to GEO under GSE226117, and were reprocessed by using the same pipeline as other tissues.

first: Tea

last: Shavlakadze

first: Romain

last: Donne

first: Corissa

last: McEwen

first: Abhilash

last: Gadi

first: Matthew

last: Wakai

first: Hunter

last: Salmon

first: Jacob

last: Treinish

first: Elias

last: Pavlopoulos

first: Larry

last: Proctor

first: Shuo

first: Nicole

last: Negron

first: Min

last: Ni

first: Yi

last: Wei

first: Yu

last: Bai

first: David

last: Glass


title: Multi-tissue, multi-time-point transcriptomic atlas of aging in mice and rats [rat]

overall_design: Bulk RNAseq of 32 tissues of male rats at 7 age groups. Samples of diaphragm, soleus, gastrocnemius, and tibialis anterior were previously submitted to GEO under GSE226118, and were reprocessed here by using the same pipeline as other tissues.

last: Li


title: Cellular Reprogramming of H3K27M Pediatric High-Grade Glioma to Neuron-like State

city: Montréal

first: Jacek

last: Majewski

state: QC

address: 740 Av. du Docteur-Penfield

department: Human Genetics

institute: McGill University

summary: This study explores the cell fate reprogrammability of H3K27M-mutant pediatric high-grade gliomas (pHGG) using neuronal transdifferentiation as a potential targeted therapy. We treated the BT245 patient-derived glioma cell line with pharmacological combinations targeting neuronal differentiation pathways and performed bulk RNA sequencing to characterize gene expression patterns driving cell fate transitions. Our findings reveal that the drug combinations induce transcriptomic changes consistent with differentiation towards mature neuronal phenotypes, including the upregulation of synaptic and dendritic signaling genes and the downregulation of malignant signatures. In comparison, astrocytic differentiation media (DM) and H3K27M knockout (KO) promote residual astrocytic or stem-like phenotypes, suggesting neuronal transdifferentiation as a more effective strategy for mitigating tumor aggressiveness and progression. Differentially expressed genes such as GRIK1, GRIN1, NRXN3, NRXN1, CALB2, SCGN, SLC32A1, SLC1A2, KCNC3, and neurodevelopmental regulators including WNT7A, DLX6, ERBB4, ARX, BCL11B, SEMA3C, and FGFBP3 were identified as key markers regulating the neuron-like lineage transition. This study demonstrates that pHGGs can be phenotypically redirected toward stable, less invasive neuronal identities through modulating cell fate differentiation programs. These findings advance the concept of 'transition therapy' as a promising intervention to reduce phenotypic plasticity and malignancy in pHGG ecosystems. While these are early in vitro findings, the ability to steer and control glioma cells toward stable, less malignant fates offers promising translational potential for patient-centered targeted therapies.

overall_design: This study aimed to reprogram H3K27M-mutant pediatric glioma cells (BT245) into less malignant neuron-like states using pharmacological differentiation therapies. Two drug combinations—FID (Forskolin, ISX9, DAPT, Laduviglusib, IBET151) and FTT (Fasudil, Tranilast, Temozolomide)—were used to induce neuronal trans-differentiation. Controls included BT245 cells in standard stem cell media or media with diluted BrainPhys, with equivalent volumes of DMSO administered across all conditions. RNA sequencing was performed to assess transcriptomic changes and infer cell identity transitions via bioinformatic analyses.

first: Abicumaran

last: Uthamacumaran

first: Cynthia

last: Horth

first: Eric

last: Bareke


title: Electromagnetic exposure changes human Schwann cells motility and transcriptomic profile of hearing-loss related genes

city: Orbassano

first: Giulio

last: Ferrero

state: TO

address: Regione Gonzole, 10

department: Dept. Clinical and Biological Sciences

institute: University of Turin

summary: Schwann cells (SCs) are glial cells of the peripheral nervous system with functional plasticity in physio-pathological conditions, as injury, and oncotransformation. Interestingly, human SCs seem to develop, mature, and respond differently to other species to environmental challenges. Recently, concerns raised about the expansion of environmental electromagnetic fields (EMF) and the increasing incidence of vestibular schwannoma (VS). We previously demonstrated that SCs respond to EMF by acquiring a state prone to oncotransformation. However, the biodependence of such transformation on the species (rodents versus human) deserves clarification. Here, we obtained and characterized human SCs, showing that EMF affects proliferation, migration, and transcriptomic profile. The expression of motility proteins increased, while those of cell-to-cell adhesion proteins decreased. The functional clustering of genes differentially expressed matched with those involved in hearing loss. In summary, we provide insights into the effects of chronic EMF on human SCs, highlighting its potential role in VS onset.

overall_design: RNA-Seq was performed on hSCs exposed to EMF or control cells, which were not exposed to EMF. For each condition, experiments were done in triplicate to performstatistics for differential expression studies

first: Tasnim

last: Mohamed

first: Alessandra

last: Colciago

first: Alessandro

last: Faroni

first: Adam

last: Reid

first: Valerio

last: Magnaghi


title: Transcriptomic Profiling of the Hypothalamic PVN in a Rat Model of Hypertension

status: Public on Mar 01 2026

city: São Paulo

first: Victor

middle: Jardim

last: Duque

state: SP

address: Rua da Contagem, 273, Porta Madeira

country: Brazil

institute: Federal University of Sao Paulo

summary: In this study, we investigated the transcriptomic profile of the Paraventricular Nucleus (PVN) in hypertensive strains and across sexes, aiming to identify novel sex-specific molecular pathways involved in the regulation of blood pressure.

overall_design: Comparative gene expression profiling analysis of RNA-seq data from the Paraventricular Nucleus (PVN) across sexes in Wistar rats and Spontaneously Hypertensive Rats (SHR)

last: Murphy

first: Nina

last: Japundžić

first: Andre

last: Mecawi


title: Cell type diversification and phenotype convergence underlying white fin-ornamentation of cyprinid fishes

city: Charlottesville

first: Delai

last: Huang

state: VA

address: 2071 Winterfield Circle

institute: University of Virginia

summary: White fin ornamentation in teleosts provides a striking model to study pigment cell diversity, differentiation, and patterning. In zebrafish (Danio rerio), white melanoleucophores (ML) and xantholeucophores (XL) produce white and yellowish-white fin patterns, respectively, arising from melanophore and xanthophore lineages. Here, we investigated white fin-pattern cells in zebrafish and a closely related cyprinid, the white cloud minnow (Tanichthys albonubes), which diverged 32–52 million years ago. We identified three distinct leucophore phenotypes in cyprinids: ML, XL, and Tanichthys leucophores, the latter containing white material but lacking substantial carotenoid pigmentation. Transmission electron microscopy revealed that XL and Tanichthys leucophores contain large pterinosome-like organelles, distinct from melanoleucophores and iridophores, suggesting different physicochemical bases for these white phenotypes. Fate-mapping in zebrafish demonstrated that XL arise directly from xanthophore-like progenitors, a process dependent on gap-junction-mediated communication via Gja5b and Cx39.4. Bulk mRNA sequencing of XL versus progenitor cells revealed upregulation of pteridine biosynthesis genes, notably sepiapterin reductase (spra), whose disruption via CRISPR/Cas9 abrogated white pigment formation in both zebrafish XL and Tanichthys leucophores. Chemical analyses confirmed enrichment of colorless pteridines, including biopterin and pterin, in tissues containing these cells. Together, our findings demonstrate that convergent white fin patterns in zebrafish and white cloud minnow rely on pteridine-based leucophores, arising via lineage-specific differentiation programs, and underscore the diversity of cellular and molecular strategies underlying white pigmentation in cyprinids.

overall_design: We collected tissue from yellow and white regions of the anal fins of Tg(aox5:palmEGFP) zebrafish at ~14 mm standard length. For each of five biological replicates, tissue from 20 fish was dissociated into a single-cell suspension, and healthy EGFP⁺ cells were isolated by fluorescence-activated cell sorting. Total mRNA was then extracted and used to generate sequencing libraries.

first: Tiffany

last: Liu

first: Yipeng

last: Liang

first: Pietro

last: H. de Mello

first: Leah

last: P. Shriverb

first: Gary

last: J. Patti

last: M. Parichy


title: Acute depletion of Cited2 in embryonic stem cells disrupts gene networks controlling self-renewal, homeostasis, and early cell fate commitment

city: Faro

first: Rui Sotero

last: Rodrigues Machado

address: Campus de Gambelas

country: Portugal

institute: Universidade do Algarve

summary: Cited2 is a transcriptional regulator essential for embryonic development and cellular homeostasis. Studies in vertebrate models highlight its critical roles in heart, placental, neural tube, and hematopoietic development. In humans, CITED2 variants are associated to congenital heart disease. Functionally, Cited2 interacts with the transcriptional co-regulators p300/CBP and modulates the activity of multiple transcription factors. In embryonic stem cells (ESC), Cited2 supports pluripotency, self-renewal, and differentiation potential. Here, we performed comparative transcriptomic analysis after acute Cited2 depletion in mouse ESC to define its role in maintaining self-renewal, lineage competence, and cell survival. Loss of Cited2 rapidly destabilized the pluripotency network and induced aberrant activation of developmental gene programs. Nodal/Activin pathway targets, including key regulators of mesoderm, cardiac, and neural development, were markedly downregulated, consistent with Cited2-null embryonic phenotypes. Cited2 depletion also altered the expression of genes involved in DNA damage response, immune signaling, and apoptosis, correlating with the increased γH2AX accumulation and p53-dependent viability loss observed. Comparison with p300- and CBP-depletion datasets revealed minimal overlap, supporting a largely p300/CBP-independent role for Cited2 in ESC. These results position Cited2 as a core regulator preserving ESC identity, genomic stability, and proper lineage engagement during early differentiation.

overall_design: 12 samples analyzed, 4 conditions with 3 replicates each. Used as reference sample is condition Day_0_ETOH_treated.

first: Leonardo

last: Mendes-Silva

first: Sara

last: Brigida

first: Marlene

last: Trindade

first: João

middle: M

last: Santos

first: Lucas

last: Rougier

first: Rui

middle: S

last: Machado

first: Ana

middle: L

last: Escapa

first: Agapios

last: Sachinidis

first: Jessica

last: MacDonald

first: José

last: Bragança


title: scRNA-seq analysis of liver nonparenchymal cells from the mouse model of CCl4-induced liver fibrosis

city: Suita

first: Seiya

last: Kato

state: Osaka

address: 2-2, Yamadaoka

department: Gastroenterology and Hepatology

institute: Osaka University

summary: We performed scRNA-seq analysis on livers from the mouse model of CCl4-induced liver fibrosis. The scRNA-seq analysis showed that CTGF expression was increased only in zone 2 LSECs, and that YAP was not activated in any cluster of LSECs.

overall_design: After liver perfusion with pronase and collagenase, hepatocytes were removed via low-speed centrifugation, and dead cells and erythrocytes were removed via density gradient centrifugation.

first: Hayato

last: Hikita

first: Tetsuo

last: Takehara


title: scRNA-seq analysis of the livers from the mice treated with a pan-integrin αV inhibitor after pIVCL

summary: We performed scRNA-seq analysis on the livers from the mice treated with a pan-integrin αV inhibitor, CWHM-12, after partial inferior vena cava ligation (pIVCL), a mouse model of congestive hepatopathy. The scRNA-seq analysis showed that integrin αV inhibition decreased the expression of YAP/TAZ target genes in pericentral LSECs and collagen expression in HSCs, caused by hepatic congestion.


title: Intrinsically Disordered Regions Form Nucleoli and Cajal Bodies While Fostering RNA Modification

city: Gosselies

first: Denis

middle: LJ

last: Lafontaine

state: Hainaut

address: Av Profs Jeneer & Brachet, 12

country: Belgium

institute: Universite libre de Bruxelles

summary: One of the densest compartments in the cell is the dense fibrillar component (DFC) of the nucleolus, consisting mainly of nascent ribosomal RNA (rRNA), small nucleolar ribonucleoproteins (snoRNPs) and their chaperone Nopp140. How this biomolecular condensate is formed and what underlies its structure is poorly understood like that of most liquid-liquid phase separated condensates. Although we established that Nopp140 is important for the cohesiveness of the DFC and for rRNA modification, it is not known how this is achieved. Here we demonstrate that Nopp140 concentrates intrinsically disordered and nuclear localization signal (NLS)-rich protein regions (IDRs), including a newly identified RNA polymerase I C-terminal domain (CTD) of the RNA polymerase I associated factor PAF49. Altogether, this network forms the DFC, a liquid-liquid phase separated biomolecular condensate that fosters rRNA modification. This mechanism ensures near 100 percent modification efficiency at some 200 nucleotides in every one of the 10 million or so rRNAs per cell.

overall_design: RiboMethSeq sequencing data from PAF49, PAF49-GFP, PAF49delta1/2IDR-GFP, and PAF49deltaIDR-GFP samples used to make the Fig.4J

first: Koceila

last: Meznad

first: Manisha

last: Deogharia

first: Ludivine

last: Wacheul

first: Christiane

last: Zorbas

first: Thomas

last: Meier


title: Gene expression microarrays of ADCY9-deficient human pancratic islets

first: Jones

last: Ofori

summary:
Adcy9-deficiency impairs stimulus-secretion coupling in β-cells
To characterize the mechanisms underlying the dysfunction caused by ADCY9-deficiency, we performed global transcriptomic analyses in human islets

overall_design: Total RNA was extracted from human islets after silencing ADCY9 using siADCY9 from human islets(N=5 donors)

first: Ofori

last: Jones

first: Ling

last: Charlotte