title: Transcriptome-wide Profiling between Cystic and Solid Vestibular Schwannoma Patients Reveal Candidate Long noncoding RNA molecular signatures

city: Jammu

first: Santhilal

last: Subhash

state: Jammu and Kashmir

address: Jagti, NH-44, PO Nagrota

department: Biosciences and Bioengineering

country: India

institute: Indian Institite of Technology Jammu

summary: Vestibular Schwannoma (VS) is a benign tumor that arises from the Schwann cells of the VIII vestibulocochlear nerve. They contribute to 6-8% of the brain tumors and 80% of tumors originate from the cerebellopontine angle. Cystic vestibular schwannoma (cVS) represents 10% of vestibular schwannomas and are associated with an unpredictable growth behavior and poor surgical outcomes compared with solid vestibular schwannoma (sVS). Long non-coding RNAs (lncRNAs) belong to the class of non-coding RNAs and are known to regulate gene transcription and involved in chromatin remodeling via various mechanism. Despite accumulating evidence demonstrating the crucial roles of lncRNAs in multiple cancers, their comprehensive identification in cVS disease remains unknown. The objective of the current study was to identify lncRNAs associated with cVS using patient cohorts. Applying next generation sequencing, we performed whole transcriptome sequencing (RNA-seq) analysis and identified lncRNAs differentially expressed between cVS and sVS.

overall_design: We have compared Cystic vestibular schwannoma (CVS) and Solid vestibular schwannoma (SVS) patient samples to find regulatory long noncoding RNAs (lncRNAs).

first: Nele

last: Teichmann

first: Mario

last: Giordano

first: Robert

last: Geffers

first: Madjid

last: Samii

first: Chandrasekhar

last: Kanduri

first: Amir

first: Souvik

last: Kar


title: JNKinhibitors for the treatment of inflammation and endometriosis [stroma]

status: Public on Jul 31 2026

city: Houston

first: FEI

last: YUAN

state: TX

address: 1 Baylor Plaza

department: Pathology & Immunology

country: USA

institute: Baylor College of Medicine

type: Expression profiling by high throughput sequencing

summary: Endometriosis is a prevalent gynecological disease that impact ~10% of women of reproductive age. In addition to causing chronic pain, and inflammation, women with endometriosis experience high rates of infertility, migraine, inflammatory bowel disease and autoimmune conditions. In this study, the efficacy of newly developed inhibitors of the c-Jun N-terminal kinases (JNK) were tested as therapeutics for endometriosis. Using state-of-the-art DNA encoded library screens, JNK inhibitors CDD-2728 and CDD-3013, with high specificity and efficacy were identified and tested in in vitro models of endometriosis. The ability of the inhibitors to decrease inflammation-related gene expression were evaluated in immortalized cell models of endometriosis, 12Z cells, and in primary derived endometriotic stromal cells from patients with the disease. Transcriptomic profiling was performed, as well as endpoints related to cell viability, cytotoxicity, and apoptosis. These studies identified that CDD-2728 and CDD-3013 were potent suppressors of IL1beta-induced inflammation, decreasing the expression of classical markers of inflammation, such as IL6, IL8, IL18, and PTGS2.

overall_design: RNAseq analysis of endometriotic stromal cells from endometriomas treated with IL1beta (10ng/ml) in the presence of absence of JNK inhibitor CDD-2728 (1µM) for 6 hours.

first: Diana

last: Monsivais

first: Stephen

last: Palmer


title: Gene expression profie at single cell level of immune cells from the deep cervical lymph nodes (dCLNs), superficial cervical lymph nodes (sCLNs), and inguinal lymph nodes (iLNs) of wild-type (WT) and Alzheimer's disease (AD) transgenic animals (5xFAD)

city: Rehovot

first: Michal

last: Schwartz

address: Herzl 234

country: Israel

institute: Weizmann Institute of Science

summary: The dCLNs are lymph nodes specialized in draining cerebrospinal fluid (CSF). We used single cell RNA sequencing (scRNA-seq) to characterize the immune cell populations in the dCLNs compared to other draining lymph nodes. We compared the immune landscape of the dCLNs between healthy WT mice and 5xFAD mice to investigate the role of dCLNs immunity in AD progression. Additionaly, we sequenced the TCR and BCR transcripts to analyze the clonal distribution of T-cells and B-cells in each lymph node.

overall_design: Cells were isolated from the dCLNs, sCLNs, and iLNs of 10-11-month-old WT and 5xFAD mice. Cells were hashed using anti-mouse Totalseq-C 001,002,003 or 004  hashtags. Gene expression (GEX), V(D)J (TCR and BCR) and Cell Surface Protein library from the same samples were then constructed using the Chromium Next GEM Single Cell 5' Reagent Kit v2 (Dual Index) with Feature Barcode technology for Cell Surface Protein and Immune Receptor Mapping.

first: Castellani

last: Giulia


title: Distinct DNA methylation landscape of IgA, IgG, and IgM ASC [ASC.RRBS]

status: Public on Jul 30 2026

city: Atlanta

first: Chris

last: Scharer

state: GA

address: 1510 Clifton Rd, Suite 3086A

department: Microbiology and Immunology

institute: Emory University

type: Methylation profiling by high throughput sequencing

summary: Antibody-secreting cells (ASCs) are critical effectors of humoral immunity, wherein their distinct isotypes play specialized roles in pathogen defense.  Despite studies defining the transcriptional programs of selected ASC isotypes, specific mechanisms underlying isotype specific gene regulation are largely unaddressed.  Here, we performed Reduced Representation Bisulfite Sequencing (RRBS) on surface-sorted IgM, IgG, and IgA ASCs isolated from the spleens and mediastinal lymph nodes of mice following influenza infection.  We observed isotype-specific DNA methylation patterns that indicate distinct functions underpin ASC of each isotype.

overall_design: 3 replicates of each of IgM, IgG, and IgA ASC were profiled by Reduced Representation Bisulfite Sequencing following influenza infection.

first: Christopher

middle: D


title: Distinct chromatin accessibility landscape of IgA, IgG, and IgM ASC [ASC.ATACseq]

type: Genome binding/occupancy profiling by high throughput sequencing

summary: Antibody-secreting cells (ASCs) are critical effectors of humoral immunity, wherein their distinct isotypes play specialized roles in pathogen defense.  Despite studies defining the transcriptional programs of selected ASC isotypes, specific mechanisms underlying isotype specific gene regulation are largely unaddressed.  Here, we performed ATAC-seq on surface-sorted IgM, IgG, and IgA ASCs isolated from the spleens and mediastinal lymph nodes of mice following influenza infection.  We observed isotype-specific chromatin accessibility patterns that indicate distinct functions underpin ASC of each isotype.

overall_design: 3 replicates of each of IgM, IgG, and IgA ASC were profiled by ATAC-seq following influenza infection.


title: Synovial transcriptomic response to intra-articular 2.5% polyacrylamide hydrogel in equine experimental osteoarthritis

city: Fort Collins

first: Steven

last: Dow

state: CO

address: 300 W Drake Rd

department: Clinical Sciences

institute: Colorado State University

summary: Background - Osteoarthritis (OA) represents one of the most common conditions treated by equine practitioners. Despite this high prevalence, no approved pharmacological intervention, biological therapy, or procedure prevents or reverses progressive destruction of degenerative joints. Intra-articular injectable polyacrylamide hydrogels (iPAAG), which consist of biocompatible non-degradable synthetic polymers, have been introduced with reported clinical efficacy. However, their potential mechanisms of action have not been fully investigated. Objectives – To determine differential gene expression in synovial tissues following intra-articular injection of 2.5% iPAAG in experimentally induced equine OA.

overall_design: Prospective randomized placebo-controlled longitudinal cohort study.

first: Lynn

last: Pezzanite

first: Lyndah

last: Chow


title: Distinct transcriptional landscape of IgA, IgG, and IgM ASC [RNA-Seq]

summary: Antibody-secreting cells (ASCs) are critical effectors of humoral immunity, wherein their distinct isotypes play specialized roles in pathogen defense.  Despite studies defining the transcriptional programs of selected ASC isotypes, specific mechanisms underlying isotype specific gene regulation are largely unaddressed.  Here, we performed RNA-seq on surface-sorted IgM, IgG, and IgA ASCs isolated from the spleens and mediastinal lymph nodes of mice following influenza infection.  We observed isotype-specific expression patterns that indicate distinct functions underpin ASC of each isotype.

overall_design: 3 replicates of each of IgM, IgG, and IgA ASC were profiled by RNA-seq following influenza infection.


title: Nup153 regulates neuronal responsiveness through HDAC1-mediated epigenetic modulation [ChIP-seq]

city: Dresden

first: Abhinav

last: Soni

state: Saxony

address: Tatzberg 41

department: Nuclear architecture in neural plasticity and aging

country: Germany

institute: German Center for Neurodegenerative Diseases, Dresden

summary: Neural activity-dependent gene regulation is central to the development of neural networks and neuronal plasticity. Induction of activity-dependent gene programs is equally important as repression of these programs, and both need to be balanced carefully. However, little is known about how repressive mechanisms modulate neuronal responsiveness across the genome before stimulation. Here, we identify nucleoporin-dependent regulation of neuronal responsiveness in which Nup153 represses neuronal genes including activity-regulated genes (ARGs) in the basal state. By characterizing the genome-wide landscape of chromatin accessibility, histone modifications and Nup153 chromatin binding, we show that Nup153 directly influences their target genes and associated chromatin states through both basal activity-dependent and -independent mechanisms. Mechanistically, Nup153 recruits HDAC1 to regulate histone acetylation and repress target chromatin regions. We propose that Nup153 acts as a structural platform to recruit epigenetic repressor to maintain activity-dependent programs in the poised state, thus maintaining neuronal responsiveness as a gatekeeper.

overall_design: 1) To investigate roles of Nup153 in regulating global histone acetylation levels in mature neurons we performed CHIP-seq for histone acetylation marker H3K27ac after Nup153 knockdown. Nup153 knockdown was performed by using shNup153-2 and shControl was used as a control shRNA. Primary cortical neurons (PCNs) at the basal state were infected for five days from DIV8 to DIV 13 before being processed for CHIP experiments. 2) To investigate genome-wide binding of histone deactylate-1 (HDAC1) we performed CHIP-Seq for HDAC1 at DIV13 basal state primary cortical neurons (PCNs).

first: Tomohisa

last: Toda


title: Nup153 regulates neuronal responsiveness through HDAC1-mediated epigenetic modulation [ATAC-seq]

overall_design: To investigate roles of Nup153 in regulating chromatin accessibility in mature neurons, we performed ATAC-seq after Nup153 knockdown. Nup153 knockdown was performed by using shNup153-2 and shControl was used as a control shRNA. Primary cortical neurons (PCNs) were infected for five days from DIV8 to DIV 13. PCNs were kept at the basal state or pre-silenced with TTX-AP5 before cell lysis and tagmentation.


title: Alterations of the tumor microenvironment (TME) in recurrent glioblastoma following apatinib in combination with temozolomide

city: Beijing

first: Junping

last: Zhang

state: Beijing

address: No. 50, Yikesong Road, District Haidian, Beijing

country: China

institute: Sanbo Brain Hospital Capital Medical University

summary: Apatinib in combination with temozolomide (TMZ) has achieved reasonable clinical efficacy in the treatment of recurrent glioblastoma (rGBM), however, there are currently no clear biomarkers related to clinical efficacy or prognosis. Our retrospective study was to investigate tumor microenvironment (TME) features at the gene expression level that are associated with response and long survival benefit of rGBM treated with apatinib and TMZ. We enrolled 22 rGBMs treated with apatinib in combination with TMZ and collected their tissue samples for RNA transcriptome analysis by the Nanostring nCounter platform.

overall_design: RNA was extracted from FFPE samples of (rGBM n=22)

first: Jing-Jing

last: Ge

first: Cheng

last: Li

first: Feng-Jun

last: Xue

first: Chi

last: Zhao

first: Chen-Chen

last: Kong

first: Shao-Pei

last: Qi

first: Qian-Qian

last: Duan

first: Qin

first: Yong-Zhi

last: Ju

first: Xia

last: You

first: Jun-Ping


title: Characteriration of mitochondrial stress response in Luhmes-derived dopaminergic neurons. Identification of open chromatin regions in stress and control conditions using ATACseq

city: Paris

first: Philippe

last: Ravassard

address: ICM 47 bd de l'hopital

country: France

institute: Paris Brain Institute

summary: Responsiveness of 6 days old differentiated Luhmes cells to mitochondrial stress induced by 8 hours treatment with Antimycin-A and Oligomycin analyzed by ATACseq. Enrichment analyses performed on genes associated with stress responsive ATACseq promoter regions validated the activation of transcriptional programs upon mitochondrial stress, in particular the engagement in the apoptotic pathway in response to ER stress as well as the alteration of neuronal identity

overall_design: 4 independent batches of differentaited Luhmes cells were treated for 8 hours with a combination of Antimycin A (25µM) and Oligomycin (10µM) and 3 independent batches of differentaited Luhmes cells  treated with vehicle (DMSO) were analyzed usqing ATACseq

first: Jana

last: Heneine

first: Hélène

last: Cheval


title: Bulk RNA-seq of alveolar type II epithelial cells from wild-type and Cry1/2 double-knockout mice with or without Nobiletin treatment.

first: Tingting

last: Mills

state: Texas

address: 6431 Fannin

institute: The University of Texas Health Science Center at Houston

summary: Chronic obstructive pulmonary disease (COPD) is a progressive inflammatory lung disease characterized by alveolar destruction and impaired tissue repair. While circadian disruption has been linked to COPD pathogenesis, the specific molecular mechanisms remain unclear. Here, we isolated primary alveolar epithelial transcriptional profiles in WT, Cry1/2-deficient epithelial cells, as well as in epithelial cells from Cry1/2-deficient mice fed Nobiletin chow. These studies will help identify key mediators of CRY1/2 as critical circadian regulators that maintain lung structure.

overall_design: Cry1 and Cry2 double knockout (Cry1/2 dKO) mice were fed with standard chow alone or standard chow supplemented with 0.1% Nobiletin (NOB) (10 mg/kg b.w.) beginning at weaning (postnatal day 25) and continued for 20 weeks.

first: Chorong

last: Han

first: Ji Ye

last: Lim

first: Sun Young

last: Kim

first: Nobuya

last: Koike

first: Zheng

last: Chen

first: Seung-hee

last: Yoo


title: RNA-seq of bronchoalveolar lavage cells from wild-type mice reconstituted with wild-type or Cry1/2 double-knockout bone marrow.

summary: Chronic obstructive pulmonary disease (COPD) is a progressive inflammatory lung disease characterized by alveolar destruction and impaired tissue repair. Although circadian disruption has been implicated in COPD pathogenesis, the underlying molecular mechanisms remain poorly understood. To examine the hematopoietic contribution of CRY1/2 to lung homeostasis, we generated bone-marrow–chimeric mice by retro-orbitally injecting 3.5 × 10⁶ bone marrow (BM) cells from Cry1/2 double-knockout (dKO) or age- and sex-matched wild-type (WT) donors into lethally irradiated CD45.1 recipient mice. Eight weeks after transplantation, bronchoalveolar lavage (BAL) cells were collected, and RNA-seq was performed to profile transcriptional changes driven by loss of Cry1/2 in the hematopoietic compartment.

overall_design: Bone-marrow–chimeric mice were generated by retro-orbitally injecting 3.5 × 10⁶ bone marrow (BM) cells from Cry1/2 double-knockout (dKO) or age- and sex-matched wild-type (WT) donors into lethally irradiated CD45.1 recipient mice.


title: Oncofetal RNA-binding proteins IGF2BP suppress innate immune signaling pathways in leukemia stem cells [ATAC-seq]

city: Hershey

first: Irina

last: Elcheva

state: PA

address: 500 University Drive

department: Department of Pediatrics

institute: Penn State College of Medicine

summary: Activation of innate inflammatory signaling and tumor-specific antigen presentation in cancer cells provides a foundation for anti-cancer immunotherapies. Here, we show that Insulin-like Growth Factor 2 mRNA-Binding Proteins (IGF2BP1, IGF2BP2, and IGF2BP3), which are upregulated across various human malignancies, including acute myeloid leukemia (AML), suppress the activity of RNA-sensing pattern recognition receptors and downstream ISRE- and NF-κB-driven transcription. IGF2BPs exert a strong inhibitory effect on RIG-I signaling. This suppression is most pronounced when all three paralogs are co-expressed, particularly in embryonic-like hematoendothelial and leukemia stem cells and is at least partly mediated through IGF2BP-dependent regulation of negative regulators of immune signaling. Genetic and pharmacological inhibition of IGF2BPs activates innate immune signaling and induces MHC class I gene expression in AML, highlighting a promising strategy for RIG-I- and TLR-based cancer immunotherapies.

overall_design: ATAC-seq and subcellular RNA-seq profiling of HEK293T cells with IGF2BP1, 2, and 3 gene knokout comparing to CRISPR/Cas9 non-targeting control. IGF2BP1, 2, 3 can be marked as IMP1, 2, 3=interchangeable gene names.

first: Karamveer

last: Karamveer

first: Yasin

last: Uzun

first: Alexis

last: Morrissey

first: Shaun

last: Mahony


title: Oncofetal RNA-binding proteins IGF2BP suppress innate immune signaling pathways in leukemia stem cells [RNA-seq]

overall_design: ATAC-seq and subcellular RNA-seq profiling of HEK293T cells with IGF2BP1, 2, and 3 gene knokout comparing to CRISPR/Cas9 non-targeting control.  IGF2BP1, 2, 3 can be marked as IMP1, 2, 3=interchangeable gene names.


title: Maternal obesity imprints methylation marks in oocytes to drive intergenerational metabolic dysfunction

city: Nanjing

first: Jiashuo

last: Li

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

institute: Nanjing Medical University

summary: Maternal obesity predisposes offspring to metabolic disease, yet how oocytes transmit this risk remains unclear. In the present study, genome-wide profiling revealed that maternal obesity induces locus-specific DNA methylation changes in oocytes. Of them, a subset of metabolic genes, particularly Hnf1α, Thra, and Pdk4, exhibited persistent transcriptional dysregulation across two successive generations. Notably, aberrant methylation at these loci was erased during embryogenesis but re-established postnatally in both germline and somatic tissues, supporting the concept of “methylation memory”. At single-CpG resolution, we identified methylation landmarks at three metabolic loci that strongly correlated with gene expression. Furthermore, by employing methylation-edited mouse model, we demonstrated that targeted oocyte hypermethylation at Hnf1α enhanced hepatic gluconeogenesis in the offspring, whereas Pdk4 hypermethylation impaired muscle glucose tolerance, both in a female-specific manner. Similarly, the elevated methylation of HNF1A and THRA was observed in oocytes from obese women. In sum, our findings provide direct causal evidence that germline methylation at defined loci can drive metabolic reprogramming across generations, highlighting the pre-conceptional period as a critical window for potential intervention in humans.

sample_organism:
Homo sapiens
Mus musculus

platform_organism:
Homo sapiens
Mus musculus

overall_design: Methylation profiling by high throughput sequencing

first: Longsen

first: Yiqiu

last: Wu


title: Combinatorial targeting of the miR-379/miR-410 cluster normalizes glucose and lipid homeostasis in male models of diabetes and obesity

city: Neuherberg

first: Stephan

last: Herzig

state: Bayern

address: Ingolstädter Landstraße 1

department: Institute for Diabetes and Cancer

institute: Helmholtz Munich

summary:
The miR-379/miR-410 cluster, belonging to the Dlk1-Dio3 locus, is the largest cluster of miRNAs in mammals. Most of its components are predicted to regulate insulin signaling, and we found consistent upregulation of the cluster in the livers of obese subjects as well as of different experimental models of insulin resistance. We have engineered a tool, a TuD, able to target two microRNAs from the cluster in a liver-specific manner. As a result, the cluster is repressed, which activates insulin signaling in the liver and leads to enhanced hepatic insulin sensitivity and reduced hepatic glucose output.
This dataset includes transcriptomics data from liver tissue of young male mice carrying hepatic-specific expression of a TuD inhibitor able to repress the miR-379/miR-410 cluster (n=6) or a negative control sequence (n=5).

overall_design: Bulk RNA-seq profiling of liver samples from C57BL/6J mice on regular chow that had received rAAVs expressing a tough decoy inhibitor (TuD) against the miRNAs miR-379 and miR-541, or a negative control sequence (NC), in a hepatocyte-specific manner. The TuD is an RNA molecule with a hairpin structure, which confers resistance to degradation, and carries two binding sites for miRNAs (in our particular case it binds the sequence of miR-379 on one of the sites and the sequence of miR-541 on the other). As a result of this manipulation the expression of the miR-379/miR-410 cluster is repressed.

first: Manuel

last: Gil-Lozano

first: Estefania

last: Simoes

first: Moya

first: Tobias

last: Wiedemann

first: Yun

last: Kwon

first: Revathi

last: Sekar

first: Pauline

last: Morigny

first: Maria

last: Troullinaki

first: Juliane

last: Merl-Pham

first: Michael

last: Buettner

first: Anette

last: Feuchtinger

first: Celine

last: Jouffe

first: Adriano

last: Maida

first: Daniela

last: Hass

first: Daniel

last: Samaga

first: Juliano

last: Machado

first: Maude

last: Giroud

first: Katarina

last: Klepac

first: Carolyn L

last: Cummins

first: Marcos

last: Rios-Garcia

first: Peter

last: Weber

first: Anja

last: Zeigerer

first: Nina H.

last: Uhlenhaut

first: Julia

last: Szendrödi

first: Matthias

last: Blüher


title: Single-Nucleus Transcriptomics Reveals Cell Type-Specific Remodeling and Epilepsy Associated Microglia

city: Los Angeles

first: Victoria

last: Ho

state: CA

address: 710 Westwood Plz

institute: University of California, Los Angeles

summary: In acquired epilepsy, an inciting injury is believed to trigger epileptogenesis, leading to dysfunctional networks that have both a propensity to give rise to seizures as well as impair normal cogntition. We have performed single nucleus sequencing on hippocampal tissue from a mouse model of temporal lobe epilepsy. The tissue was collected during time-points at which seizures and memory deficts are just begining to emerge. We anticipate this dataset will allow for the identification of key changes underlying epileptogenesis and provide candidates for therapeautic intervention.

overall_design: Status epilepticus (SE) was induced in wild-type mice using systemic pilocarpine to model temporal lobe epilepsy. Littermates were used as control. Dorsal hippocampi were collected at 3- and 6-week post-SE and processed for single-nucleus RNA sequencing.

middle: M

first: Peyman

last: Golshani


title: RNA-seq profiling of SEM B-ALL cells silenced for KMT2A::AFF1 fusion circular RNA.

city: Segrate

first: Ingrid

last: Cifola

state: Milan

address: Via F.lli Cervi, 93

department: Institute for Biomedical Technologies (ITB)

country: Italy

institute: National Research Councill (CNR)

summary: The t(4;11) translocation, resulting in the KMT2A::AFF1 fusion gene, is associated with a poor prognosis in pediatric and adult B-cell Acute Lymphoblastic Leukemia (B-ALL). Recently, KMT2A::AFF1 fusion circular RNAs (f-circRNAs) were identified by bioinformatics in B-ALL; however, their contribution to leukemia has not been explored. In this context, we identified a novel recurrent back-splicing junction joining the AFF1 exon 8 to KMT2A exon 2 (AK_8_2), which was recurrent in t(4;11)-positive B-ALL cell lines as well as in pediatric and adult B-ALL patients. To investigate its functional role, we performed the total RNA-seq profiling of SEM B-ALL cells harboring the t(4;11) translocation and knocked-down for AK_8_2 f-circRNA, thus identifying a set of up-regulated genes potentially relevant for cell metabolism and leukemogenesis.

overall_design: We performed the total-RNAseq profiling of three independent replicates of SEM cells silenced and not for AK_8_2 f-circRNA.

first: Marco

last: Severgnini

first: Clelia Tiziana

last: Storlazzi

first: Grazia

last: Fazio

first: Giovanni

last: Cazzaniga


title: Unravelling the immune signalling pathways in dual and triple Toll-like Receptor (TLR) agonists combination in chickens

city: Bareilly

first: Saravanan

last: Ramakrishnan

state: Uttar Pradesh

address: Izatnagar

department: Immunology Section

institute: Indian Veterinary Research Instittue

summary: Toll-like receptors (TLRs) are innate receptors playing key role in innate immunity and further shaping the adaptive immunity. Simultaneous activation of different TLRs results in cross-talk and can lead to either synergistic or antagonistic effects on the immune responses. Toll-like receptor (TLR) agonists are used as immunomodulatory agents and as vaccine adjuvants in human and chickens. Combinations of different TLR agonists are being explored to alleviate systemic toxicity and achieve long-lasting desirable immune responses. Dual (R-848/TLR7 and CpG-ODN/TLR21) and Triple (LPS/TLR4; R-848/TLR7 and CpG-ODN/TLR21) TLR agonists induced immune response in chicken were analysed through spleenic transcriptome. Our data, helps to understand the mechanistic basis and key molecules behind the dual/triple-TLR signalling in chicken, which can be tailored to achieve desired immune response and improve efficacy of therapeutic formulations.

overall_design: Four week old specific pathogen free white leghorn birds (three biological replicates per group) were injected intramuscularly with dual (R-848 and CpG-ODN) and triple (LPS, R-848 and CpG-ODN) TLR agonists combination keeping PBS injected control group. 24 hour post-stimulation, spleen samples were harvested from all birds of control and treated groups for RNA profiling.

first: Abinaya

last: Kaliappan

first: Khushboo

last: Panwar

first: Prasad

last: Thomas

first: Naveen

last: Dumala

first: Surya

middle: K

last: Varma

first: Mithilesh

last: Singh

first: Sohini

last: Dey

first: Madhan

last: Chellappa


title: DNMT3B drives neuroendocrine lineage plasticity and aggressive progression in prostate cancer

city: Durham

first: Jung Wook

last: Park

state: NC

address: 905 South Lasalle St.

department: Pathology

institute: Duke University

summary: Neuroendocrine prostate cancer (NEPC) is an aggressive, treatment-resistant subtype of prostate cancer characterized by poor prognosis and limited therapeutic options. In this study, we identify de novo DNA methyltransferase 3B (DNMT3B) as a critical driver of NEPC growth and neuroendocrine differentiation. We demonstrate that DNMT3B expression is significantly upregulated during prostate cancer progression and is essential for NEPC cell proliferation, as its genetic inhibition via CRISPR-Cas9 and inducible shRNA systems impairs tumor growth and promotes apoptosis both in vitro and in vivo. Transcriptomic profiling reveals that DNMT3B loss disrupts cell cycle regulation and suppresses neuroendocrine lineage programs by downregulating key transcription factors such as FOXA2, NEUROD1, SOX2, and INSM1. Moreover, DNMT3B is required for both the initiation and maintenance of NEPC in a human genetically engineered prostate cancer model. Pharmacological inhibition of DNMT3B with Nanaomycin A selectively suppresses NEPC tumor growth and attenuates neuroendocrine marker expression without causing systemic toxicity. These findings establish DNMT3B as a central regulator of NEPC and support its potential as a therapeutic target for this lethal cancer subtype

overall_design: NEPC cell lines transduced by lentiviruses expressing sgSCR or sgDNMT3B

first: JungWook

first: Yunsol

last: Jo

first: David

last: Lee

first: Brandon

last: Tsai

first: Andrew

last: Tran

first: Issac

last: Jung

first: Yuzhuo

last: Wang

first: Ziqin

first: Sanjeevram

last: Dhandapani

first: Jiaoti

last: Huang


title: SPEN is an androgen receptor dependent tumor suppressor and mediates hormonal therapy resistance in prostate cancer

city: Seattle

first: Sonali

last: Arora

state: WA

address: 1100 Fairview Ave N,

institute: FHCRC

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

overall_design: Refer to individual Series


title: Pdgfrα deficiency in islet b-cells up-regulates apoptosis 1 of beta-cells and disturbs 2 glucose metabolism in B6 mice

city: New Haven

first: Li

last: Wen

address: 300 Cedar Street

institute: Yale Univeristy

summary: We generated β-cell-specific Pdgfrα-deficient C57BL/6 mice (Pdgfrafl/fl Pdx1-cre+) and assessed their metabolic function on both a normal and a high fat diet. We found that the Pdgfrα-deficient mice gained significantly more body weight, with more body fat, poorer glucose metabolism, and the β-cells were more apoptotic and had lower insulin content. Our further mechanistic investigations showed that Pdgfrα deletion suppressed Atf5 by down regulation of PI3K, leading to enhanced β-cell apoptosis. Atf5 regulates Gadd45b, Bcl2 and aminoacyl-tRNA synthetase expression and alters insulin biosynthesis and glucose metabolism. Targeting these β-cell apoptotic factors may provide an opportunity for improving preventive and/or therapeutic strategies for diabetes and beyond.

first: Luyao

last: Zhang

first: Yanpeng

last: Xing

first: Pai


title: SARS-CoV-2 variants divergently infect and damage cardiomyocytes in vitro and in vivo

city: Hong Kong

first: Maxwell

last: Kwok

address: The Chinese University of Hong Kong, Shatin

country: Hong Kong

institute: The Chinese University of Hong Kong

summary: SARS-CoV-2 variants are known to exhibit different tropism and pathogenicity in respiratory cells, but their effect on cardiomyocytes (CMs) is unclear. Cardiac infection and damage induced by SARS-CoV-2 variants were examined using human induced pluripotent stem cell-derived (hiPSC-) CMs. Different variants exhibited distinct tropism, mechanism of viral entry and pathology in the heart. Omicron BA.2 efficiently infected CMs in vitro and in vivo, induced the most severe phenotype, and exhibited transcriptomic changes indicative of increased cardiac dysfunction, compared to other variants tested. Bioinformatics analysis identified transcription factors predicted to regulate the unique transcriptome induced by Omicron BA.2. Increased infectivity of Omicron BA.2 is attributed to its ability to infect independently of TMPRSS2, which is absent in CMs. Here we reveal previously unknown differences in how different SARS-CoV-2 variants infect and damage CMs.  Omicron BA.2, which is generally considered mild, is capable of inducing severe CM damage in vitro and in vivo. Our study highlights the need for further investigations to define the pathogenesis of cardiac complications arising from different SARS-CoV-2 variants.

overall_design: Comparative gene expression profiling analysis of RNA-seq data for hiPSC-CM infected with different variants of SARS-CoV-2

first: Bobo

middle: W

last: Mok

first: Hung

middle: S

last: Li

first: Ellen

middle: N

last: Poon


title: CRISPR data for prostate cancer cell line(LNCaP) from Day0 , treated with either DMSO, Enzalutamide or synthetic androgen (R1881)

summary: Prolonged use of androgen deprivation therapy (ADT) inevitably renders all hormone sensitive prostate cancer into castration-resistant prostate cancer (CRPC). Improved androgen receptor (AR) targeting therapies, such as enzalutamide, have led to advances for the treatment of CRPC, however, the disease undergoes remodeling of the phenotypic landscape leading to direct AR resistance and transdifferentiation. To identify novel regulators of enzalutamide resistance, we performed a genome-wide CRISPR-Cas9 knockout screen in a hormone sensitive prostate cancer cell line grown in enzalutamide. We discovered that loss of the AR cofactor SPEN (also known as SHARP) results in dramatic resistance to enzalutamide but no growth advantage in control conditions. This finding is supported by a large whole exome sequencing patient data set showing SPEN is one of the most commonly mutatedgenes in advanced prostate cancer with clonal variants enriched in metastases. SPEN is a large protein with numerous functions including steroid receptor binding, transcriptional repression through its interaction with NCOR/SMRT, and as an RNA binding protein (RBP). Interestingly, RNA-Seq in enzalutamide treated SPEN KO cells showed up-regulation of gastrointestinal (GI) lineage genes as well as steroid hormone metabolism genes. Given its function as an RBP, we tested if enzalutamide resistant SPEN knockout prostate cancer cells resulted in changes in translation. We observed a rapid increase in translation suggesting this process plays a role in therapy resistance. Polysome profiling also showed increased RNA abundance on polysomes. Moreover, polysome RNA-seq showed up-regulation of transcripts involved in GI-associated and steroid hormone metabolism pathways. To test for a functional role of the SPEN domain in driving castration-resistance by selectively targeting this repressor complex to a subset of pro-oncogenic genes, we have generated a DNA integrase landing pad at the AAVS safe harbor locus which permits doxycycline inducible rescue of each SPEN domain deleted construct. These studies will form the basis for further mechanistic studies and development of new therapeutics for CRPC patients.

first: Steven

last: Blinka

middle: C

last: Hsieh


title: Single-cell transcriptomic profiling of splenic cells under chronic anemia in mice

city: Singapore

first: Rui

last: Yokomori

address: 14 Medical Drive

country: Singapore

institute: Cancer Science Institute of Singapore, National University of Singapore

summary: Single cell RNA-seq analysis for spleen tissue isolated from mice subjected to chronic phenohydrazine (PHZ) and bleeding (BLD) treatment respectively.

overall_design: C57BL/6 mice were subjected to PHZ injection or bleeding every 3 days for one month to induce chronic anemia. Live cells were isolated from spleens under each condition. Single-cell suspensions were prepared and processed using the 10x Genomics Chromium platform.

first: Chong

last: Yang

first: Toshio

last: Suda


title: Polysome seq of treated with Enzalutamide and untreated (DMSO)prostate cancer cell line with SPEN wt and SPEN KO

first: Andrew


title: Decoding Lymphangioleiomyomatosis (LAM) Niche Environment via Integrative Analysis of Single Cell Multiomics and Spatial Transcriptomics

city: Cincinnati

first: Yan

last: Xu

state: OH

address: 3333 Burnet Ave

institute: Cincinnati Children's Hospital Medical Center

summary: Lymphangioleiomyomatosis (LAM) is a rare, progressive lung disease characterized by cystic destruction and metastatic growth of smooth muscle-like cells. Despite advances in understanding its genetic basis, the cellular heterogeneity, regulatory mechanisms, and microenvironmental interactions driving LAM progression remain poorly defined. We identified two spatially and functionally distinct LAM subtypes: LAMCORE1 and LAMCORE2. LAMCORE1 cells exhibited a uterine smooth muscle-like phenotype, expressing associated markers (ACTA2, MYH11) and were enriched in MTORC1 signaling and myogenic pathways, supporting a uterine origin. In contrast, LAMCORE2 cells displayed fibroblast-like features, with upregulated extracellular matrix (ECM) remodeling genes (COL1A1, MMP11) and epithelial-to-mesenchymal transition (EMT) pathways, suggesting a role in niche formation. Pseudotime and regulon analyses revealed dynamic transitions between these subtypes, driven by distinct transcriptional networks (e.g., HOX/PBX in LAMCORE1, TWIST/ZEB in LAMCORE2). The presence of the two distinct LAM subtypes was further validated by RNAscope and immunofluorescence microscopy.

overall_design:
Employed an integrative multi-omics approach combining single-cell RNA sequencing (scRNA-seq), single-nucleus ATAC sequencing (snATAC-seq), and high-resolution spatial transcriptomics (Visium, Visium HD, and Xenium) to decode the LAM niche in its native environment. We identified two spatially and functionally distinct LAM subtypes: LAMCORE1 and LAMCORE2.

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Raw files for human/patient samples are being made available in dbGaP (https://www.ncbi.nlm.nih.gov/gap/) for controlled access to the personally identifiable sequence data.
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first: Ken

last: Chen

first: Shuyang

last: Zhao

first: Minzhe

last: Guo

first: Hasan

last: Reza

last: Wagner

first: Adnan Cihan

last: Cakar

first: Cheng

last: Jiang

first: Erik

first: Jenna

last: Green

first: Emily

last: Martin

first: Kathryn

last: Wikenheiser-Brokamp

first: Anne

last: Perl

first: Debora

last: Sinner

first: Jane

last: Yu


title: Single nucleus RNA-sequencing atlas of pediatric solid tumors

city: Memphis

first: Michael

last: Dyer

state: TN

address: 262 Danny Thomas Pl MS 324

department: Developmental Neurobiology

institute: St. Jude Children's Research Hospital

summary: single-nuclei RNA-sequencing on a large cohort of patient tumors and O-PDXs. This research proposal will fill a fundamental gap in our knowledge of the transcriptome heterogeneity across pediatric solid tumor clones and of the normal cells found in the tumor microenvironment.

first: Jackie L

last: Norrie

first: Anand G

last: Patel

first: Michael A


title: Identification of plasma exosomal miRNAs as predictive biomarkers for therapeutic efficacy of programmed cell death 1 (PD-1) blockade plus chemotherapy in gastric cancer patients

city: Baotou

first: yunqi

last: hua

address: 18 Tuanjie Street, Qingshan District, Baotou City, Inner Mongolia Autonomous Region

department: 1.Medical oncology 2.Department of Public Health

institute: 1.Baotou Cancer Hospital2.International College, Krirk University

type: Non-coding RNA profiling by high throughput sequencing

summary: Background: The response of gastric cancer (GC) patients to first-line programmed cell death 1 (PD-1) blockade plus SOX chemotherapy varies considerably, and the underlying mechanisms remain elusive. Exosomal microRNAs (miRNAs) have emerged as potential biomarkers for efficacy prediction due to their roles in GC biology and stable expression in serum. Here, we aimed to explore biomarkers that may predict response to anti-PD-1 therapy and further elucidate the potential mechanism. Methods: Serum exosomes were extracted from 11 GC patients (5 in primary cohort and 6 in the validation cohort) treated with SOX and camrelizumab (a PD-1 inhibitor). High-throughput sequencing identified miRNA expression profiles, followed by hierarchical clustering and differential expression analysis. Functional enrichment analysis of target genes for significantly upregulated miRNAs was performed using Gene ontology (GO) and Kyoto encyclopedia of genes and genomes (KEGG) databases. Validation of candidate miRNAs was carried out using quantitative polymerase chain reaction (qPCR) in an independent cohort.   Results: MiRNA sequencing identified 3083 miRNAs, with 74 differentially expressed between responders and non-responders (42 upregulated and 32 downregulated). GO and KEGG pathway analysis of the top 20 upregulated miRNAs indicated significant involvement of target genes in transcription regulation, cytoplasmic processes, and protein binding, with key pathways including PI3K-AKT, MAPK, RAP1, and RAS signaling. QPCR validation demonstrated significant differences in the expression levels of miRNA451a and miRNA142-5p between responders and non-responders, consistent with sequencing findings. Conclusion: Our study identifies specific plasma exosomal miRNAs that differentiate between responders and non-responders to PD-1 monoclonal antibody therapy combined with chemotherapy in GC patients. These miRNAs hold potential as predictive biomarkers, paving the way for precision medicine and personalized therapy in GC treatment.

overall_design: We observed variations in the clinical efficacy of PD-1 monoclonal antibody combined with chemotherapy in the treatment of advanced gastric cancer. We analyzed the differential expression of miRNA in the serum exosomes of patients with good and poor efficacy and investigated their roles.


title: Depletion of lamin-associated polypeptide 2 alpha leads to chromatin reorganization and redistribution of A-type lamins to open genomic regions [ATAC-seq]

city: Vienna

first: Roland

last: Foisner

address: Dr.-Bohr-Gasse 9

country: Austria

institute: Max Perutz Labs, Medical University of Vienna

summary:
Background: Lamins are major regulators of the spatial and functional organization of chromatin. Lamins at the nuclear periphery form the lamina that anchors heterochromatin to the nuclear envelope. A subpool of A-type lamins localizes in the nuclear interior, where they also bind to euchromatic genomic regions. A-type lamin properties and chromatin association are regulated by lamin-associated polypeptide 2alpha (LAP2α). Here we systematically analyze, how LAP2α depletion affects chromatin organization, accessibility and gene expression on a genome-wide level.
Results: LAP2α depletion in mouse dermal fibroblasts positively and negatively affects chromatin accessibility and gene expression throughout the genome, which correlates with changes in chromatin association of A-type lamins and the nucleosomal remodeler proteins BRG1 and CHD4. In particular, A-type lamins translocate to open chromatin regions closer to BRG1 and CHD4 binding sites and deregulated genes, but do not directly accumulate on genes and BRG1 and CHD4-enriched sites. Unsupervised clustering of the datasets on LAP2α-bound genomic regions confirms spreading of A-type lamins to active chromatin regions containing deregulated genes, and an enrichment of chromatin remodelers on a subset of these genomic regions.
Conclusions: LAP2α depletion in fibroblasts leads to a gross rearrangement of chromatin. Genome-wide chromatin reorganization is linked to spreading of A-type lamins to active chromatin regions and accompanied by a restriction of chromatin remodelers to a subset of active genomic regions. These changes correlate with changes in chromatin accessibility and gene expression throughout the genome and particularly in regions, where lamin binding is gained in LAP2α knockout versus wildtype cells.

This research was funded in whole or in part by the Austrian Science Fund (FWF) [P32512-B and P36503-B] to Roland Foisner, and a doctorate program funded by the Austrian Science Fund (FWF) [W1261-B28]. Daria Filipczak is recipient of a DOC Fellowship of the Austrian Academy of Sciences  (ÖAW DOC 25912); This work is also supported by a Marie Jahoda fellowship of the University of Vienna to Nana Naetar.

overall_design: The assay for transposase-accessible chromatin with sequencing (ATAC-Seq) of wildtype and Lap2alpha KO mouse dermal fibroblast.

first: Daria

last: Filipczak

first: Fatih

last: Sarigol

first: Daniel

last: Malzl

first: Nana

last: Naetar


title: Impact of iPSC EVs on Immune Cells from Mouse Lymph Nodes

first: Xia

last: Yang

address: 610 Charles E. Young Drive East

summary: Extracellular vesicles (EVs) secreted by adult stem cells, particularly mesenchymal stem cells (MSCs), have garnered significant attention for their regenerative potential across various pathological conditions. However, despite this promise, the clinical translation of MSC EVs remains limited due to challenges such as donor variability and the finite proliferative capacity of MSCs, which pose significant obstacles to their therapeutic application. In contrast, pluripotent stem cells (PSCs), including induced pluripotent stem cells (iPSCs), exhibit unlimited expansion potential when cultured under optimized conditions. This exceptional proliferative capacity enables the large-scale production of both PSCs and their EVs, making them highly attractive for therapeutic development. Additionally, embryos can achieve immune tolerance, yet the underlying mechanisms remain incompletely understood. We hypothesized that PSC EVs are enriched with a unique set of immunoregulatory molecules capable of modulating immune cells and promoting tolerance. To further explore the effects of iPSC EVs on immune cells within the lymph nodes, we performed single-cell RNA sequencing (scRNA-seq) using the 10x Genomics platform.

overall_design: Wildtype C57BL/6 mice were treated with a total of 100 µg of iPSC EVs via subcutaneous injection. After 5 days, draining lymph nodes were harvested and dissociated into single-cell suspensions. Immune cells from lymph nodes were harvested from experimental and control animals and single cell suspensions were isolated and ran using the 10x 3′ single-cell RNA-seq V3.1 protocol.

first: Graciel

last: Diamante

first: Jana

last: Zarubova

first: Mohammad Mahdi

last: Hasani-Sadrabadi

first: Song

last: Li


title: Depletion of lamin-associated polypeptide 2 alpha leads to chromatin reorganization and redistribution of A-type lamins to open genomic regions [ChIP-seq]

overall_design: Chromatin immunoprecipitation DNA-sequencing (ChIP-seq) for BRG1, CHD4, Lamin A/C and Lap2alpha in wildtype and Lap2alpha KO mouse dermal fibroblast sonicated for 16 and 20 cycles.


title: Targeting phosphodiesterase 8A (PDE8A) and adipogenesis to promote hair regeneration

city: Xiamen

first: Lingjuan

last: Zhang

address: Xiangan South Street

institute: Xiamen University

summary: To maximally capture adipocytes and hair follicle keratinocytes, which are largely lost through enzymatic digestion in scRNA-seq, we performed single-nuclei RNA sequencing (Sn-RNAseq) of the developing mouse skin samples. The aim of this analysis was to identify key cell-cell interactions between adipocytes and hair follicle keratinocytes. Briefly, dorsal skin biopsies were collected from the developing C57BL/6 pups (at postnatal day 2) and 10x Genomics Sn-RNAseq was applied to identify distinct cell populations. After low quality nuclei and outliers were discarded, ～16481 nuclei were used for downstream bioinformatic analyses, including Unsupervised clustering, marker gene expression, and Cell-Chat signaling network analyses. Overall, our results reveal that adipocytes secrete growth factor to support hair follicle growth.

overall_design: To isolate single-nuclei, fresh P2 skin tissues were preserved by snap freezing in liquid nitrogen, transferred to a dounce homogenizer, grinded into a homogenate in lysis buffer. Nuclei were extracted by repeated washes with nuclear resuspension buffer and sucrose cushion buffer, then isolated nuclei were further purified by DAPI staining and sorting. Single nuclei were loaded on a 10x Genomics GemCode Single-cell instrument that generates single-cell Gel Bead-In-EMlusion (GEMs). single-nuclei libraries were prepared using Chromium Next GEM Single Cell 3’ Reagent Kits v3.1. cDNA libraries were sequenced on an Illumina Novaseq6000 platform (Illumina). After low quality nuclei and outliers were discarded, ～16481 nuclei were used for downstream bioinformatic analyses. Unsupervised clustering and gene expression were visualized with the Seurat on R studio, and assignment of cell clusters was based on expression of validated marker genes. The R package CellChat version 1.3.0 was applied to study the cell-cell interactions between adipocytes and hair follicle keratinocytes.

first: Ling-juan


title: MAOA+ CAFs enforce immune exclusion in pancreatic cancer by restraining serotonin-dependent histone H3Q5 serotonylation

status: Public on Jul 29 2026

city: Xi'an

first: dengxu

last: Tan

address: Changlexilu

department: Laboratory Animal Center

institute: Fourth Military Medical  University

summary: Pancreatic ductal adenocarcinoma (PDAC) is characterized by dense desmoplasia and profound T-cell exclusion, yet the stromal metabolic programs that sustain this immune-refractory microenvironment remain poorly understood. Monoamine oxidase A (MAOA) is a mitochondrial enzyme that catalyzes serotonin degradation, but whether this metabolic pathway is co-opted by cancer-associated fibroblasts (CAFs) to regulate antitumor immunity remains unknown.

overall_design: Here, we identify MAOA-expressing CAFs as a previously unrecognized serotonin-catabolic stromal population that establishes an immune-excluding niche in PDAC. Integrative analyses of patient specimens, single-cell transcriptomics, genetically engineered mouse models, humanized mice, and patient-derived organoid coculture systems demonstrated that MAOA was selectively enriched in FAP+ CAFs, with approximately 75% of FAP+ CAFs expressing MAOA. High stromal MAOA expression was associated with reduced CD8+ T-cell infiltration and poor patient survival. Genetic ablation or pharmacological inhibition of CAF-intrinsic MAOA reprogrammed immune-excluding CAFs into a chemokine-competent state, enhanced CD8+ T-cell recruitment, suppressed tumor growth, and improved the therapeutic efficacy of PD-1 blockade. Mechanistically, MAOA inhibition induced intracellular serotonin accumulation, increased H3Q5 serotonylation and H3K4me3 enrichment at the MSK1 promoter, promoted phosphorylation-dependent MSK1 activation, and subsequently enhanced NF-κB/p65-mediated CCL5 transcription. Neutralization of CCL5 or depletion of CD8+ T cells abolished the antitumor effects of MAOA inhibition, demonstrating that stromal MAOA promotes immune evasion by reprogramming CAFs rather than through direct tumor cell cytotoxicity. Collectively, these findings establish CAF-derived MAOA as a stromal monoamine-catabolic checkpoint that enforces immune exclusion through serotonin-dependent epigenetic regulation of CCL5 and identify MAOA inhibition as a therapeutic strategy to enhance the efficacy of PD-1 blockade in PDAC.

first: Dengxu


title: Interrogating DNA methylation associated with Lewy body pathology in a cross brain-region and multi-cohort study

city: Exeter

first: Joshua

last: Harvey

state: Devon

address: RILD Building, RD&E, Barrack Road

department: Clinical and Biomedical Sciences

country: United Kingdom

institute: University of Exeter

type: Methylation profiling by genome tiling array

summary: In this study we investigated DNA methylation association with Lewy body pathology, profiled genome wide using this Illumina EPIC bead chip array in a set of brain samples sourced from the UK Brain Bank Network from centres at Newcastle, Imperial College London, University College London and Oxford. Data was generated from 779 samples, sourced from 406 unique donors (n = 387 Anterior Cingulate Cortex (ACC), n = 392 Prefrontal Cortex (PFC)). Following quality control, linear modelling approaches were used to assess DNA methylation loci association with Lewy body pathology as measured by the Braak staging criteria. This data was meta analysed alongside two prior established cohorts (Netherlands Brain Bank and Brains for Dementia Research).

overall_design: Brain tissue was ground over liquid nitrogen and underwent DNA extraction using the Qiagen AllPrep DNA/RNA/miRNA Universal kit according to the manufacturer’s instructions and stored at 4°C. 500ng of DNA from each sample was bisulfite treated using the Zymo EZ-96 DNA methylation Gold kit. Methylomic profiling was completed after sample randomization using the Illumina Infinium MethylationEPIC v1.0 BeadChip. Data processing was performed using R, using the minfi and wateRmelon packages.

first: Jennifer

last: Imm

first: Katie

last: Lunnon

first: Ehsan

last: Pishva


title: RNA-seq on in vitro 3D structure of Klf5-KO biliary epithelial cells

city: Mishima

first: Hajime

last: Okada

state: Shizuoka

address: Yata 1111

country: Japan

institute: National Institute of Genetics

summary: In Klf5 knockout mice, the ductular reaction upon cholestatic liver injury is severely suppressed. We developed an in vitro 3D branching system that mimics the ductular reaction. In this system, the biliary cells were detached from the branching structure when Klf5 was lost. In order to unravel the roles of Klf5 and identify its target molecules that function to prevent the cells from detaching, we conducted RNA-seq analysis on the biliary cells from 3D in vitro branching structure.

overall_design: Single-end RNA-seq of total RNAs extracted from biliary structures in vivo after the loss of Klf5 (12 hours and 24 hours)

first: Minami

last: Yamada


title: Distinct activation programs in naïve and memory CD8 T cells govern progeny stemness and effector persistence (multiome, OT-I. Day 0 as control, Day 7 and Day 12)

city: Prague

first: Juraj

last: Michalik

address: Vídeňská 1083

country: Czech Republic

institute: Institute of Molecular Genetics of the Czech Academy of Sciences

summary: We longitudinally profiled gene expression in naive and central and effector memory CD8+ T cells across multiple models of acute cognate infection to reveal subset-specific activation programs. However, how prior antigen experience alters T-cell activation programs remains poorly understood. We longitudinally profiled gene expression in naive, central memory, and effector memory CD8+ T cells in response to cognate antigen across multiple models of acute infection. Naive T cells engaged TOX- and TCF7-centered programs and generated early stem-like central memory precursors. Their initially slow proliferation was followed by rapid expansion and the production of large numbers of effector cells. Central memory T cells rapidly triggered effector and proliferation programs while maintaining a smaller self-renewing population. Effector memory T cells expanded poorly and generated almost exclusively effector progeny. Effector progeny derived from both memory subsets survived contraction more efficiently than naive T-cell-derived progeny and established persistent effector memory populations. These data show that prior antigen experience does not simply accelerate CD8+ T-cell activation but redirects cell-intrinsic programs governing progeny fate and persistence. These distinct programs may reflect adaptation to different histories and anticipated patterns of antigen exposure.

overall_design: The analysis compares samples from OT-I mice infected by Lm-OVA and Tcm, Tem and Tn progeny (TM used as control at day 0).

first: Eva

last: Salyova

first: Darina

last: Paprckova

first: Veronika

last: Niederlova

first: Ondrej

last: Stepanek


title: Single-nucleus transcriptomic analysis of aging and hepatocyte-specific ADK reduction in mouse liver

city: College Station

first: Chaodong

last: Wu

state: TX

address: 373 Olsen Blvd

department: Nutrition

institute: Texas A&M University

summary: Aging is associated with extensive transcriptional and cellular changes in the liver, including the emergence of metabolically dysfunctional and stress-responsive hepatocyte states. Adenosine kinase (ADK) is a key regulator of intracellular and extracellular adenosine homeostasis; however, its contribution to age-associated liver remodeling remains incompletely understood. To characterize liver aging at single-nucleus resolution and investigate the role of hepatocyte ADK, we performed single-nucleus RNA sequencing of liver tissues from 3-month-old wild-type mice, 18-month-old wild-type mice, and 18-month-old mice carrying hepatocyte-specific ADK wild-type or heterozygous alleles. Comparative transcriptomic analyses were used to identify age-associated changes in hepatic cell populations, characterize distinct hepatocyte states, and determine how partial reduction of hepatocyte ADK influences aging-related transcriptional programs. This dataset provides a resource for investigating cellular heterogeneity, hepatocyte aging, and ADK-dependent regulation in the aged mouse liver.

overall_design: Single-nucleus RNA sequencing was performed on mouse liver tissues representing young, aged, and hepatocyte-specific ADK genotypes. The study included four experimental conditions: 3-month-old wild-type mice, 18-month-old wild-type mice, 18-month-old hepatocyte-specific ADK+/+ mice, and 18-month-old hepatocyte-specific ADK+/− mice. Nuclei were isolated from frozen liver tissues and processed using the 10x Genomics Chromium Single Cell Gene Expression Flex platform. The four samples were labeled with distinct sample-specific probe barcodes and pooled prior to library preparation and sequencing. The raw sequencing files therefore represent a multiplexed pool, while individual biological samples were distinguished computationally based on their corresponding probe barcode identities. Comparisons between 3-month-old and 18-month-old wild-type mice were used to identify age-associated changes in liver cell composition and gene expression. Comparisons between 18-month-old hepatocyte-specific ADK+/+ and ADK+/− mice were used to evaluate the effects of partial hepatocyte ADK reduction in the aged liver. Downstream analyses focused on liver cell-type heterogeneity, hepatocyte transcriptional states, aging-associated gene programs, lipid and metabolic pathways, and stress-responsive hepatocyte populations. The four samples were labeled with distinct sample-specific probe barcodes and pooled prior to library preparation and sequencing. The raw sequencing files therefore represent a multiplexed pool, while individual biological samples were distinguished computationally using their corresponding probe barcode identities.

first: Honggui

first: Xinlei

last: Guo

first: Xiaojing

first: Miaoyun

last: Chen


title: Distinct activation programs in naïve and memory CD8 T cells govern progeny stemness and effector persistence (mixed) [memory_scRNAseq_exp34]

overall_design: The analysis compares samples from OT-I, Vb5 and Endogenous mice infected with Lm-OVA at D3 (OT-I) or D7/D10 (Vb5) or with LCMV (Endogenous) of different progeny (Tn, Tcm, Tem).


title: Distinct activation programs in naïve and memory CD8 T cells govern progeny stemness and effector persistence (single cell experiment, OT-I mice, Lm-OVA infection, Day 6)

overall_design: Here we compared different cell types (Tem, Tcm and Tn) from multiple samples using single-cell analysis.


title: Multidimensional Evaluation of UC-MSCs: Comparative Therapeutic Efficacy of Intrathecal and Intravenous Administration in a Rat Traumatic SCI Model

city: TIANJIN

first: HAO

last: YU

address: Building B3, TianDa Science and Technology Park, No. 80 Fourth Avenue, TEDA,Tianjin，China

institute: Tianjin AmcellGene Engineering Co., Ltd.

summary: Spinal cord injury (SCI) is a disabling neurological disorder with very limited therapeutic strategies. Human umbilical cord derived mesenchymal stem cells (UC MSCs) have shown therapeutic potential for SCI, but the optimal administration route remains undetermined. This study compared the efficacy and mechanisms of GMP grade UC MSCs delivered via intrathecal (MSC i.t) and intravenous (MSC i.v) injection in a rat traumatic SCI model.

overall_design: Forty rats with Allen's method induced SCI were randomly assigned into four groups (n=10): sham, SCI, MSC i.v (3×10⁷ cells/kg), and MSC i.t groups (1×10⁷ cells/kg). Cells were administered twice at 72 hours and 7 days post injury, respectively. Outcome measures included BBB score, MRI, histopathology, ELISA, immunofluorescence, scRNA seq, and in vivo bioluminescence imaging.

first: Hao

last: Yu


title: Distinct activation programs in naïve and memory CD8 T cells govern progeny stemness and effector persistence (single cell experiment, OT-I mice, Lm-OVA infection,Week 12)

overall_design: Here we compared different cell types (Tn(Tem), Tn(Tcm), Tem, Tcm) from multiple samples using single-cell analysis.


title: Cellular context restricts IDR plasticity to a single essential effector interface for m6A-dependent mRNA turnover [Chan_RNA-seq_experiment 1]

city: London

first: Folkert

last: van Werven

address: 1 Midland Road

institute: Francis Crick Institute

summary: N6-methyladenosine (m6A) is a conserved mRNA modification that regulates transcript stability, yet how m6A reader proteins engage effectors remains poorly understood. Using yeast meiosis as a model, we investigated how the YTH-domain protein Pho92 promotes decay of m6A-modified transcripts through its intrinsically disordered region (IDR). In vitro, the Pho92 IDR makes multiple contacts with the Ccr4-NOT deadenylase complex and drives tethered reporter decay in the absence of any single subunit. Yet in meiosis, turnover of endogenous m6A-modified transcripts strictly depends on a single interface: direct binding of the Pho92 IDR to Caf40. A single hydrophobic residue substitution is sufficient to abolish Caf40 binding and halt transcript decay. Human YTHDF proteins can functionally substitute for Pho92, but require multiple hydrophobic patches within the IDR for decay activity. Thus, the cellular context of meiosis dictates which IDR-mediated contacts are functional for m6A turnover, adding a layer of specificity in post-transcriptional gene regulation.

overall_design: Depletion of 9 RNA regulatory factors during early meiosis in yeast.

first: Wei

last: Chan

first: Duncan

last: Berger

first: James

last: Booth


title: Cellular context restricts IDR plasticity to a single essential effector interface for m6A-dependent mRNA turnover [Chan_RNA-seq_experiment 3]

overall_design: CUP induced expression Pho92 IDR mutants


title: In vitro transcriptomics and molecular dynamics reveal palmatine as a topical candidate against psoriasis via targeting LCK to co-regulate NF-κB and Wnt signaling pathways

city: Harbin

first: Yuan-hong

last: Wang

address: 24 Heping Road

institute: First Hospital of Heilongjiang University of Chinese Medicine

summary: Psoriasis is a chronic inflammatory skin disorder characterised by immune dysregulation and aberrant keratinocyte hyperproliferation. Traditional Chinese medicine (TCM) formulae are widely used to alleviate psoriatic symptoms; however, their complex chemical compositions have long impeded the identification of core bioactive constituents. This study aimed to screen for anti‑psoriatic components from two representative TCM formulae using network pharmacology, and to further validate the therapeutic efficacy and molecular mechanism of palmatine—a major alkaloid derived from Phellodendron chinense—against psoriasis. Network pharmacology was employed to predict the potential targets of the primary constituents of P. chinense, which were then intersected with psoriasis‑associated genes retrieved from the OMIM (Online Mendelian Inheritance in Man) and GeneCards databases. An in vitro psoriasis‑like model was established by stimulating HaCaT cells with IL‑17A. Cell viability assay, cell cycle analysis, and Western blotting were performed to evaluate the pharmacological effects of palmatine. Transcriptomic profiling combined with bioinformatics analysis was used to identify key signalling pathways. Molecular docking and 100‑ns molecular dynamics (MD) simulations were conducted to screen and validate the core target proteins. Palmatine shared a substantial number of targets with psoriasis‑related genes and effectively reversed IL‑17A‑induced S‑phase arrest in HaCaT cells. A total of 736 differentially expressed genes were identified, with significant enrichment in the NF‑κB and Wnt signalling pathways. Molecular docking revealed that palmatine bound tightly to IKBKB, LYN, and LCK, and MD simulations further confirmed that the LCK–palmatine complex exhibited favourable structural stability throughout the 100‑ns trajectory. Palmatine exhibits considerable anti‑psoriatic activity in the in vitro setting, potentially through targeting LCK and modulating the NF‑κB and Wnt signalling pathway. This study provides a novel candidate compound and a precise molecular target for the research and development of anti‑psoriatic therapeutics.

overall_design: HaCaT human keratinocytes were cultured and stimulated with IL‑17 to establish an in vitro psoriasis‑like inflammatory model. Cells were then treated with palmatine to evaluate its transcriptional modulatory effects. Total RNA was extracted from each sample and subjected to high‑throughput RNA sequencing to profile global gene expression changes.

first: Yuan-Hong

first: Tong

first: Xiao-Xue

last: Zhang

first: Hui-Ge

first: Qian-Yue

last: Ni

first: Xuan

first: Hao-Ran


title: Transcriptomic profiling reveals IGF2BP1-mediated gene regulation and Helicobacter pylori-induced transcriptional reprogramming in gastric epithelial cells

city: Beijing

first: Jing

last: Ning

state: Not required for this country

address: 49 North Garden Rd.,Haidian District，

institute: Peking University Third Hospital

summary: Helicobacter pylori infection induces persistent transcriptional reprogramming in gastric epithelial cells. To identify downstream pathways regulated by IGF2BP1, RNA sequencing was performed in GES-1 cells with IGF2BP1 overexpression and H. pylori infection. Integrated analysis identified overlapping transcriptional programs associated with oxidative stress regulation and ferroptosis-related pathways.

overall_design: RNA-seq was performed in GES-1 gastric epithelial cells under two experimental conditions: IGF2BP1 overexpression and Helicobacter pylori infection. Differential expression analysis was performed to identify shared transcriptional responses associated with IGF2BP1 activation and bacterial infection.

first: Xin

last: Guan

first: Shigang

last: Ding


title: Expression profile of bone marrow mesenchymal stem cells cultured on poled and non-poled PVDF films

city: Derio

first: Ana

middle: Maria

last: Aransay

state: BIZKAIA

address: Parque tecnologico de Bizkaia, Building 801-A

department: Genome Analysis Platform

country: Spain

institute: CIC bioGUNE

summary: In the current study, we systematically analyzed the response of human bone marrow-derived mesenchymal stem cells to PVDF substrates with different permanent surface electric charges but equivalent roughness, ligand densities, wettability, and rigidity.

overall_design: Human bone Marrow-derived mesenchymal Stem cells (MSCs) were cultured on PVDF films with different surface electric potentials (nehagite, positive and net neutral) coated with equal amounts of collagen type I. At the given timepoints (24 hours and 4 days after seeding) RNA was extracted and the gene expressing signature analyzed.

first: Sara

last: Martín-Iglesias

first: Cristina

last: Eguizabal

first: Juan

last: Anguita

first: Unai

last: Silvan


title: Cardiac fibroblast deletion of PTBP1 modulates the profibrotic response by alternative splicing II

city: Chapel Hill

first: Shea

last: Ricketts

address: 111 Mason Farm Road

department: Pathology and Laboratory Medicine

institute: UNC Chapel Hill

summary: In this project we investigate the role of RNA binding protein PTBP1 in cardiac fibrosis through the conditional deletion of PTBP1 in mouse cardiac fibroblasts and discovered PTBP1 binds to downstream target Fgfr1. We probed FGFR1 in cardiac fibroblasts from C57BL/6 mice by either shRNA mediated global knockdown or overexpression of FGFR1 isoform constucts. We then stimulated cardiac fibroblasts with TGFb to perform deep RNA sequencing studies on the cardiac fibroblast to myofibroblast transformation.

overall_design: RNAseq profiling of FGFR1 depleted (shFgfr1) cardiac fibroblasts with wildtype controls (shNT) with and without profibrotic stimulation via TGFb. RNAseq profiling of FGFR1 isoform overexpression cardiac fibroblasts with wildtype controls (LacZ) with and without profibrotic stimulation via TGFb. RNA was isolated with Qiagen RNeasy Plus Mini Kit according manufacturers protocol. Three independent biological replicates were used for each experimental group and sequencing studies were performed to quantify transcript expression.

first: Li

last: Qian


title: Integrated Transcriptomic and Immune Analysis Reveals Distinct Mitochondrial and Immune Signature in COVID-19 ARDS Requiring Invasive Mechanical Ventilation

city: Houston

first: Deepa

middle: B.

last: Gotur

address: 6565 Fannin

department: Medicine

institute: Houston Methodist Hospital

summary: Patients requiring Invasive Mechanical Ventilation (IMV) compared to patients who are non-Invasive Mechanical Ventilation (non-IMV)demonstrated distinct transcriptomic and immune profiles associated with severe COVID-19. These findings identify candidate biomarkers and pathways associated with disease severity; however, the results are exploratory and require validation in larger cohorts and functional studies.

overall_design: Patients (n = 36) with SARS-CoV-2 infection requiring oxygen support were enrolled in this prospective study. Blood samples were collected at baseline, day 4, and day 8 from patients on IMV (n=11) and non-IMV (n=25). Transcriptomic profiles of peripheral blood mononuclear cells were assessed using RNA-sequencing, followed by gene ontology and KEGG pathway enrichment. Plasma cytokines and chemokines were measured using multiplex immunoassays, peripheral immune cell endotypes were characterized by mass cytometry, and neutrophil extracellular trap (NET) formation was evaluated by kinetic live-cell imaging.

middle: B


title: Tailored FcγR blockade enhances immune checkpoint therapy and overcomes resistance

city: Lund

first: Björn

last: Frendeus

state: Skane

address: Ideongatan 1

country: Sweden

institute: BioInvent International

summary: We conducted single-cell RNA sequencing using the 10x Genomics Chromium Next-GEM Flex protocol to investigate the mechanism of action behind the improved therapeutic efficacy of anti-CTLA4 seen when combined with FcgrII blockade. Our goal was to understand the mechanism of action of the combination of anti-CTLA4 and anti-FcgrII in comparison to anti-CTLA4 single treatment. These studies provide new insights and role of FcgrII blockade as therapeutic target in cancer.

overall_design: Humanized CTLA-4 mice (B-hCTLA-4, Biocytogen) were inoculated subcutaneously with 0.5 million MC38 cells. Mice were treated intraperitoneally with anti-human CTLA-4 (ipilimumab, human IgG1, 10 mg/kg Apoteket), anti-mouse FcgRII (AT130-2 mIgG1-N297A 20 mg/kg, in house), a combination of anti-human CTLA-4 and anti-mouse FcgRII or isotype control (hIgG1, 10 mg/kg, in-house) when the tumors reached a size of approximately 100 mm3. Day 8 after start of treatment, CD45+ cells were isolated from the tumors (after 3 treatments) using Fluorescence-activated cell sorting (FACS) and analyzed using scRNA-seq.

first: Niyaz

last: Yoosuf

first: Petra

last: Holmkvist

first: Linda

last: Mårtensson

first: Monika

last: Semmrich

first: Ingrid

last: Teige


title: Effect on flg22 treatment on Col-0, hir2-2, and hir2-5 seedlings

city: Tübingen

first: Hannah

middle: Lena

last: Weber

state: Baden-Württemberg

address: Auf der Morgenstelle 32

department: Biochemistry

institute: ZMBP Tübingen

summary: We here analyze the response of Col-0, hir2-2, and hir2-5 seedlings to flg22. HIR2 was shown to interact with PAMP-involved receptor-like kinases and signalling proteins. Furthermore, hir2 mutants are alterred in their ROS response upon PAMP treatment.

overall_design: RNA-seq profiling of wildtype Col-0 and hir2 mutant seedlings. For each sample, 7 seedlings grown for 10 days on ½ MS were treated with either water (mock) or 1 µM flg22 for 10 min and then frozen in liquid N2. The RNA was extracted using the RNeasy Plant Kit (Qiagen) and diluted to a concentration of 150 ng. The RNA quality was checked with a NanoDrop (Thermo Fisher) and its integrity with Bioanalyzer (Agilent RNA 6000 Pico). RNA sequencing was performed by Eurofins (NovaSeq 6000 S4 PE150 XP), and bioinformatic analysis was performed.

first: Birgit

last: Kemmerling


title: Regulation of Hematopoietic Inflammatory Signaling by MIRC11 and miR-146a

city: South Bend

first: Richard

last: Dahl

state: IN

address: Harper Hall 227, 1234 Notre Dame Ave.

department: Microbiology and Immunology

institute: Indiana University School of Medicine, South Bend

summary: Disruption of inflammatory pathways contributes to hematopoietic disorders such as leukemia, cytopenias, myelo-dysplastic syndromes (MDS), and myeloproliferative diseases (MPD). Although chronic inflammation impairs normal hematopoiesis, a low level of inflammatory signaling is essential for maintaining hematopoietic stem cell (HSC) homeostasis. Here, we report that mice lacking MiRNA Cluster 11 (Mirc11: encodes miR-23a, miR-24-2, and miR-27a) display reduced inflammatory signaling, including diminished IFN-α/β, IFN-γ, TNF, IL-6, and Toll-like receptor (TLR) pathway activity. Notably, this phenotype is opposite of that seen in miR146a-deficient mice, which exhibit hyperinflammation leading to bone marrow failure. These contrasting phenotypes suggest that Mirc11 miRNAs and miR-146a may function together to buffer inflammatory signaling and maintain immune homeostasis.

overall_design: Sequenced total RNA obtained from Lin-Sca1+cKit+ bone marrow cells obtained from cohorts of wildtype and Mirc11 deleted mice.

first: Dahl

last: Richard

first: Boucher

last: Austin

first: Rao

last: Sridhar


title: Predicting relevant microglia-associated cell-cell communication pathways in Alzheimer’s disease: a role for SPP1

city: Groningen

first: Bart

last: Eggen

state: Groningen

address: Antonius Deusinglaan 1

department: Department of Biomedical Sciences

country: Netherlands

institute: UMCG Groningen

summary: Microglia play a key role in the pathophysiology of Alzheimer’s Disease (AD) and their increased heterogeneity likely affects disease progression. We previously identified distinct microglial signatures that were enriched in AD donors and associated with amyloid and tau, respectively. Here we analyzed cell-cell communication pathways that might be relevant to AD pathophysiology. We generated a snRNAseq dataset from postmortem control and AD cases and analyzed alterations in cell-cell communications. One signaling pathway perturbed in AD cases involved SPP1, and while this pathway was also present in control samples, microglia-microglia SPP1 signaling was restricted to AD donors. Further analyses within microglia-microglia signaling predict AD-specific induction of GAS6-AXL signaling (from inflammatory and ribosomal microglia), and SPP1-ITGAV/ITGB5 signaling (from disease-associated and inflammatory microglia, among others). Together, these findings might in part explain the increased microglia phagocytic profile described in AD.

overall_design: Single-nucleus RNAseq transcriptomes were generated from fresh frozen occipitotemporal cortex brain samples. A total of ten samples were processed, five from donors with Alzheimer's disease, and five from non-neurological controls.

first: Janssen

last: Kotah

first: Marina

last: Trombetta-Lima

first: Esmée

last: Dragt

first: Asimenia

last: Voulgaroglou

first: Nieske

last: Brouwer

first: Inge

last: Holtman

first: Susanne

last: Kooistra


title: Pathophysiological insights into ACO2-related inherited disorders through combined functional and multi-omic analyses of ACO2 patient-derived fibroblasts

city: ANGERS CEDEX 01

first: Cléis

last: Beaulieu

address: 40 RUE DE RENNES

institute: UNIVERSITE D'ANGERS

summary: ACO2 encodes the mitochondrial aconitase, involved in the second step of the tricarboxylic acid cycle. ACO2 variants cause isolated dominant or recessive optic atrophy, characterized by the degeneration of the optic nerves and leading to vision loss with high clinical heterogeneity, which ranges from pauci-symptomatic to legally blind patients. ACO2 variants also cause rare severe syndromic presentations, like infantile cerebellar-retinal degeneration, characterized by developmental delay, truncal hypotonia, ataxia, seizures, optic atrophy and retinal degeneration.  As ACO2 pathophysiology still lacks proper characterization and no treatment is available for ACO2-related disorders, we combined a functional study with a multi-omic analysis of patient-derived fibroblasts carrying ACO2 variants. Here, we show that ACO2 variants decrease ACO2 protein levels, ACO2 and cytoplasmic ACO1 mRNA expression and mtDNA levels. Metabolomic analyses identified 14 discriminating metabolites involved in amino acid metabolism, TCA cycle, nucleotide and lipid metabolism. Transcriptomic analyses disclosed a down-regulation of immunity-related pathways and an up-regulation of cell cycle-related pathways. These results provide new insights into the cellular impact of ACO2 deficiency beyond its primary role in the TCA cycle, and identify citrate accumulation as a crucial determinant in ACO2 physiopathology.

overall_design: RNA-seq profiling of skin fibroblasts from patients with ACO2 variants exhibiting either isolated optic neuropathy (2 patients : Dominant Optic Atrophy, DOA; Recessive Optic Atrophy, ROA) or infantile cerebellar-retinal degeneration (2 patients : ICRD1, ICRD2). Differential gene expression was performed against 4 control cell lines from healthy individuals.

first: Aymane

last: Bouzidi

first: Cinzia

last: Bocca

first: Ismail

last: Gouiza

first: Naïg

last: Gueguen

first: Valérie

last: Desquiret-Dumas

first: Béatrice

last: Vary

first: Majida

last: Charif

first: Magalie

last: Barth

first: Morgane

last: Le Mao

first: Florence

last: Pascaretti-Grizon

first: Adélie

last: Mellinger

first: Nolwenn

last: Bounaix

first: Delphine

last: Prunier-Mirebeau

first: Salim

last: Khiati

first: Marco

last: Spinazzi

first: Arnaud

last: Chevrollier

first: Olivier

middle: R

last: Baris

first: Guy

last: Lenaers


title: Splenic B cells Accumulate and Adopt a Pro Inflammatory Phenotype to Accelerate Fibrosis in a CCl₄ Induced Liver Fibrosis Model

city: Xi’an, Shaanxi

first: Keping

last: Feng

address: No. 157, Xiwu Road

institute: The Second Affiliated Hospital of Xi'an Jiaotong University

summary: Introduction and Objectives: The spleen plays a significant role in hepatic fibrosis progression. B cells are the main splenic lymphocytes, but their specific contributions and underlying mechanisms remain unclear. Materials and Methods: Hepatic fibrosis was induced in mice by intraperitoneal administration of carbon tetrachloride (CCl₄). Splenectomy or sham operation was performed during the fibrotic process. Hepatic fibrosis severity and the proportion of splenic B cells were assessed. Splenic B cells isolated from fibrotic and control mice underwent mRNA sequencing. Protein expression levels of p38 MAPK and NF-κB pathway components (phosphorylated-p38 MAPK [p-p38 MAPK], total p38 MAPK, phosphorylated-NF-κB p65 [p-NF-κB p65], total NF-κB p65) were determined by Western blotting using total protein extracted from splenic B cells. Signal transduction pathways were investigated in isolated splenic B cells to elucidate mechanisms of phenotypic alteration. Results: CCl₄-induced hepatic fibrosis was associated with B-cell accumulation in both the liver and spleen. Compared with the splenectomized mice, sham-operated fibrotic mice exhibited a higher proportion of hepatic B cells and more severe liver fibrosis. Splenic B cells from fibrotic mice showed an expansion of the IL-6-producing subset and elevated expression of pro-inflammatory cytokines. Moreover, splenectomy reduced the proportion of B cells within the fibrotic liver. Splenic B cells from fibrotic mice displayed upregulated expression of p-p38 MAPK and p-NF-κB p65. Conclusions: In CCl₄-induced hepatic fibrosis, splenic B cells accumulate and adopt a pro-inflammatory phenotype. This shift, mediated through activation of the p38 MAPK/NF-κB signaling pathway, promotes hepatic fibrosis progression. These findings identify splenic B cells as potential therapeutic targets for managing liver disease.

overall_design: RNA-seq profiling of splenic B cells from wildtype and the fibrotic mice after 4 weeks of CCl₄ intraperitoneal injections


title: SETD8-mediated mono-methylation of YAP at K76 promotes K48-linked polyubiquitination and degradation to suppress colorectal cancer

city: Wuhan

first: Nie

last: Haihang

address: donghu road 169

institute: Zhongnan Hospital of Wuhan University

summary: Yes-associated protein (YAP), a key effector of the Hippo pathway, plays a well-established role in colorectal cancer (CRC). However, the functional relevance of site-specific post-translational modifications (PTMs) in YAP, particularly methylation, remains insufficiently explored. SET-domain-containing protein 8 (SETD8), the sole monomethyltransferase for histone 4 lysine 20 (H4K20), is implicated in various cancers, yet its biological function and underlying mechanisms in CRC are elusive. While SETD8 is primarily known for its histone methylation activity, its capacity to modify non-histone proteins, such as YAP, remains largely unexplored. This study aimed to demonstrate that SETD8 exerted a tumor-suppressive effect on CRC by inhibiting YAP protein expression. Mechanistically, SETD8 physically interacts with YAP to catalyze monomethylation at lysine 76 (K76me). This modification enhances the interaction between YAP and the E3 ubiquitin ligase RING finger protein 31 (RNF31), promoting YAP K48-linked polyubiquitination and subsequent proteasomal degradation. Clinically, patients with CRC and high SETD8 expression, including elevated YAP K76me levels, exhibited favorable pathological grading and improved prognosis. Collectively, our findings identify a novel SETD8-YAP K76me regulatory axis that restricts CRC progression, suggesting that targeting this axis may represent a promising therapeutic strategy.

overall_design: RNA-seq analysis of HCT116 cells transfected with empty vector plasmid or SETD8 overexpression plasmid.

first: Yali

last: Yu

first: Haihang

last: Nie

first: Hailin

last: Wang

first: Jiang

last: Wu

first: Fei

last: Xu

first: Mei

last: Ye


title: Paternal methionine supplementation alters DNA methylation patterns in preimplantation sheep embryos

city: Madison

first: Hasan

last: Khatib

state: Wisconsin

address: 1675 Observatory Drive

department: Animal and Dairy Sciences

institute: University of Wisconsin Madison

summary: Parental environmental factors can shape developmental outcomes through epigenetic mechanisms that regulate gene expression. While maternal dietary effects on offspring epigenetics have been well characterized, the impact of paternal diet on embryonic DNA methylation remains poorly understood. Here, we investigated the effect of paternal methionine supplementation on DNA methylation patterns in preimplantation embryos in Polypay sheep. Four prepubertal rams (two control and two methionine-supplemented) were bred to twelve ewes following estrus synchronization and superovulation. Embryos were collected after natural mating and analyzed using whole-genome bisulfite sequencing (WGBS). A total of 842 differentially methylated cytosines (DMCs) were identified in embryos derived from methionine-supplemented sires compared to controls, with 835 hypermethylated and 7 hypomethylated. The majority of DMCs were located in intergenic regions, with minimal representation in exonic regions. To assess overlap between parental dietary effects, DMCs identified in this study were compared with those previously reported in embryos derived from methionine-supplemented dams. Eight hypermethylated DMCs were shared between the two datasets, while no hypomethylated DMCs overlapped. To evaluate the functional relevance of differentially methylated genes, we performed siRNA-mediated knockdown of SSU72, a gene associated with multiple DMCs. Knockdown of SSU72 resulted in an average 18% decrease in blastocyst formation rate (p < 0.001). These results demonstrate that paternal methionine supplementation alters embryonic DNA methylation patterns and that affected genes may play critical roles in early embryonic development, contributing to fetal programming.

overall_design: Four prepubertal rams (two control-diet and two methionine-supplemented) were bred to twelve control-diet fed ewes following estrus synchronization and superovulation. Embryo pools were collected after natural mating and analyzed using whole-genome bisulfite sequencing (WGBS).

first: Jessica

last: Townsend

first: Zeynep

last: Kizilaslan

first: Mehmet

first: Todd

last: Taylor


title: Transcripts identified by RNAseq analysis that were deregulated in E12.5+18h cultures of murine ureters upon treatment with LiCl.

city: Hannover

first: Mark-Oliver

last: Trowe

address: Carl-Neuberg-Str. 1

department: Molekularbiologie

institute: Medizinische Hochschule Hannover

summary: Evaluation of the transcriptional changes in murine E12.5+18h ureters upon treatment with LiCl.

overall_design: Ureters of NMRI embryos (E12.5) were dissected and cultured for 18h in medium containing 15 mM LiCl or in medium without LiCl. Total RNA from these ureters was analyzed by RNAseq analysis.

first: Andreas

last: Kispert

first: Florian

last: Bergmann


title: Multi-tissue microphysiological system captures integrated responses to nutritional overload and metabolic therapy

city: St. Petersburg

first: Oscar

middle: E

last: Ospina

state: FL

address: 600 5th Street South

department: Health Informatics

institute: Johns Hopkins All Children's Hospital

summary: This study used a human six-tissue microphysiological system to examine how shared multi-tissue interaction, graded nutrient exposure, and pharmacologic perturbation shape tissue-specific transcriptional programs relevant to systemic glucose regulation. The MOTIVE-6 platform integrated hiPSC-derived midbrain organoids, intestinal epithelium, liver organoids, pancreatic islets, visceral adipocytes, and skeletal muscle in a shared circulating media environment. Bulk RNA-seq was performed on individual tissue compartments after four days of culture under Low, Mid, or High nutrient conditions, with additional High-nutrient conditions treated with metformin or semaglutide. Matched isolation cultures were used to distinguish transcriptional effects associated with multi-tissue interaction from those observed in independently cultured tissues. This dataset enables analysis of tissue-specific responses to inter-tissue signaling, nutrient state, and anti-diabetic drug exposure in a perfused human multi-tissue model.

overall_design: Human tissue compartments representing midbrain, intestine, liver, pancreatic islets, visceral adipose tissue, and skeletal muscle were cultured either together in the MOTIVE-6 six-tissue microphysiological system under shared perfusion or as matched isolation controls. Interaction cultures were exposed to Low nutrient media (6 mM glucose/0.5% lipid), Mid nutrient media (12 mM glucose/2% lipid), High nutrient media (18 mM glucose/4% lipid), High nutrient media plus metformin (1 μg/mL), or High nutrient media plus semaglutide (130 ng/mL). Drug-treated cultures received metformin or semaglutide on days 0 and 2 of the four-day experiment. After four days of culture, each tissue compartment was harvested separately for bulk RNA-seq. For multi-tissue interaction experiments, one fully assembled MOTIVE-6 vessel containing all six tissue compartments was treated as one biological replicate, with one RNA-seq sample generated from each harvested tissue compartment. For isolation experiments, one independently cultured matched tissue preparation under the corresponding media condition was treated as one biological replicate. The dataset supports comparisons between interaction and isolation culture, across graded nutrient conditions, and between untreated High nutrient exposure and High nutrient exposure with metformin or semaglutide treatment.

first: Martin

last: Trapecar

first: Marissa

last: McGilvrey


title: Gene expression profiling of ES2 cells with or without UAP1 knocked down (Control versus siUAP1)

city: Hong Kong

first: Michelle

middle: KY

last: Siu

address: Laboratory Block, FMB, 21 Sassoon Road, Pokfulam

department: O&G

institute: University of Hong Kong

summary: To determine the potential downstream pathways of UAP1 in ovarian cancer cells

overall_design: RNA-Seq analysis of ES2 cells with UAP1 knockdown by siUAP1 and corresponding control cells

first: Jiangnan

last: He

first: Michelle KY


title: CAMKV Kinase Signaling Is a Novel Therapeutic Avenue with Prognostic Relevance in Neuroblastoma

city: Washington

first: Yang

last: Yu

state: DC

address: 111 Michigan Ave NW

institute: Children's national hospital

summary: High-risk neuroblastoma (NB) remains a leading cause of childhood cancer mortality, with survival rates below 50% despite intensive multimodal therapy. Tumor progression is frequently driven by MYCN amplification or MYC overexpression, yet direct pharmacologic targeting of these oncogenic transcription factors has proven challenging. Here, we identify CaM kinase-like vesicle-associated protein (CAMKV), previously considered a pseudokinase, as a MYCN/MYC-regulated kinase that promotes NB tumor growth. Genetic depletion of CAMKV inhibited NB cell proliferation and suppressed tumor growth in vivo. Bioinformatic analyses and immunohistochemical staining of primary tumors revealed that elevated CAMKV expression correlates with poor patient survival. Integrated proteomic and transcriptomic profiling demonstrated that CAMKV regulates oncogenic signaling networks essential for NB pathogenesis. Notably, pharmacologic inhibition of CAMKV significantly impaired tumor progression in preclinical models. Together, these findings establish CAMKV as a unifying therapeutic vulnerability and highlight it as a druggable kinase candidate for translational development in high-risk NB.

overall_design: ChIP-seq analysis was performed using an anti-CREB antibody in the human neuroblastoma cell line NGP. Integrated analysis of the ChIP-seq data and shRNA-mediated knockdown results identified the direct transcriptional targets of the CAMKV-CREB signaling axis in neuroblastoma.

first: Jianhua

last: Yang


title: Microfibril denudation marks early aortic vulnerability in SMAD3 variant carriers: a multigenerational study

city: London

first: Paulina

last: Kowalewska

state: Ontario

address: 1151 Richmond Street

department: Robarts Research Institute

country: Canada

institute: The University of Western Ontario

summary:
Background: Individuals with Loeys-Dietz syndrome 3 (LDS3) are at risk for thoracic aortic dissection even if their aortas are not substantially dilated. A pathogenic variant of SMAD3 is a genetic trigger, but the cellular programs that underlie the heightened aortic risk remain poorly understood.
Methods: We ascertained the cardiovascular profile of 57 individuals in a four-generation family with a missense variant in SMAD3 (p.Arg287Gln). Aortic medial architectures were quantified from aortas harvested during thoracic aortic replacement surgery, with 2D and 3D profiling of the elastin-microfibril network. TGF-beta-dependent regulatory networks were investigated by whole-genome RNA sequencing of ascending aortic smooth muscle cells (SMCs) and bioinformatics-informed chromatin immunoprecipitation.
Results: Cardiovascular phenotypes of family members harboring the SMAD3 variant included thoracic aortopathy, peripheral artery aneurysms and tortuosity, cerebrovascular disease, coronary artery dissections, and mitral valve prolapse. The median age at the first aortic event was 36.5 years. Ascending aortas were less dilated than the aortic root, with relatively intact lamellar structure and SMC content. However, early pathology was evident, with SMCs separated from elastic lamellae by a thin layer of glycosaminoglycans. Confocal reconstructions revealed that elastic fibers were poorly decorated by microfibrils, with reduced fibrillin-1, fibrillin-2, microfibril associated glycoprotein-2, fibulin-1 and fibulin-2. RNA sequencing of LDS3 SMCs revealed reduced expression of microfibrils. Furthermore, Paired Related Homeobox 2 (PRRX2) was found to be down-regulated in LDS3 SMCs in culture and in situ, occupy gene promoter sites for all five microfibrils, and mediate their expression in SMCs. SMAD3 overexpression rescued both PRRX2 and microfibril expression.
Conclusions: These findings identify SMCs delaminating from unsheathed elastic fibers as an incipient pathological program in LDS3 aortas. They also uncover a SMAD3-PRRX2-microfibril axis that, being perturbed, could explain this disconnection phenomenon and contribute to risk.

overall_design: RNA paired-end sequencing was performed on RNA isolated from human ascending aortic smooth muscle cells (passage 1) of 3 control subjects and 3 LDS3 (test) subjects.

first: Hao

last: Yin

first: Mofei

last: Wang

first: Brittany

last: Balint

first: Sahar

last: Hoveyda

first: Usha

last: Manian

first: Pei Jun

last: Zhao

first: Joshua

last: Samsoondar

first: Kevin

last: Fan

first: Zengxuan

last: Nong

first: Caroline

last: O'Neil

first: Matthew

last: Hare

first: Julieta

last: Lazarte

first: Sharan

last: Goobie

first: Robert

last: Hegele

first: Michael

last: Chu

first: Geoffrey

last: Pickering


title: Asiatic acid from Centella asiatica alleviates renal fibrosis: coordinated modulation of the gut–kidney axis and retinol metabolism

city: Suzhou

first: liwei

last: zhu

state: Jiangsu

address: 77th, Changan South Street

institute: Zhangjiagang TCM Hospital Affiliated to Nanjing University ofChinese Medicine

summary: Chronic kidney disease (CKD) is a progressive condition characterized by renal fibrosis, with limited treatment options. Asiatic acid (AA), a triterpenoid derived from Centella asiatica, has shown renoprotective potential as a dietary supplement. This study integrated 16S rRNA sequencing, renal metabolomics, transcriptomics, and Metorigin analysis to investigate the renoprotective effects of AA in an adenine-induced CKD mouse model. AA significantly improved renal function, attenuated fibrosis, restored gut barrier integrity. Antibiotic depletion experiments demonstrated that an intact gut microbiota is required for the renoprotective effects of AA, supporting a functional link along the gut–kidney axis. AA modulated gut microbiota composition, notably enriching the beneficial genus Lachnospiraceae NK4A136 group. Multi-omics integration identified retinol metabolism as the key renal pathway rescued by AA, with metabolites including 9-cis-retinal and 4-hydroxyretinoic acid (4-OH-RA) showing strong negative correlations with renal injury markers.In vitro, 4-OH-RA suppressed fibrotic injury and oxidative stress in TGF-β1 stimulated tubular cells. These findings suggest that AA alleviates CKD in association with remodeling of the gut microbiota and reprogramming of renal retinol metabolism, highlighting its potential as a microbiota-targeting dietary supplement for renal protection., supporting its potential as a dietary supplement for countering renal fibrosis and supporting kidney health.

overall_design: Control (C, normal diet), CKD model (M, 0.25% adenine diet),  High-dose Asiatic acid (AA, adenine diet + 30 mg/kg AA).

first: Liwei

last: Zhu

first: Ziyun

last: Xu

first: Xiaoyan

last: Chang

first: Jingyi

last: Wu

first: Zhenfang

last: Du

first: Haiyong

last: Chen

first: Sheng

last: Qiang


title: Hepatic FoxO3 Supports Metabolic Resilience, Attenuates Age-Associated Obesity and Metabolic Dysfunction, and Mitigates Diet-Induced Steatohepatitis

city: Nagasaki

first: Toshimitsu

last: Komatsu

state: Nagasaki

address: 1-12-4 Sakamoto

department: Biomedical Research Support Center

institute: Nagasaki University School of Medicine

summary: Forkhead box O3 (FoxO3) is implicated in aging and metabolic regulation; however, its roles in the local and systemic control of aging remain incompletely understood. In this study, we characterized the effects of hepatocyte-specific Foxo3 deletion on hepatic metabolic and whole-body energy homeostasis during aging, and the susceptibility of mice to metabolic disease. Male hepatocyte-specific Foxo3 knockout (h-Foxo3-/-) mice developed moderate obesity and higher plasma insulin levels by middle age, despite no difference in food intake compared with wild-type mice. Indirect calorimetry revealed lower energy expenditure relative to body weight, a higher respiratory quotient, and less fatty acid oxidation, indicating a shift toward carbohydrate-dependent energy metabolism. Adipose tissue exhibited inflammatory cell infiltration and high expression of inflammatory and senescence markers, consistent with systemic insulin resistance. Although these findings suggested that hepatokine signaling regulates systemic metabolism, there was limited direct evidence for FoxO3-dependent hepatokine secretion. RNA-sequencing analysis suggested that fatty acid processing and xenobiotic and detoxification pathways were suppressed in h-Foxo3-/- liver and that gluconeogenic and proinflammatory programs were activated. h-Foxo3-/- mice exhibited hepatic steatosis and an increase in the oxidized glutathione concentration when consuming a regular diet, and those consuming a fat-, fructose-, and cholesterol-rich diet, which induces steatohepatitis, showed more severe fibrosis than controls. Collectively, these findings suggest that hepatic FoxO3 is a key regulator coordinating hepatic lipid processing, xenobiotic metabolism and detoxification, susceptibility to metabolic disorders, and systemic metabolic flexibility. Thus, hepatic FoxO3 contributes to the maintenance of metabolic resilience during aging.

overall_design: RNA sequencing (RNA-seq) was performed on liver tissues from floxed control and hepatocyte-specific Foxo3 knockout (KO) mice under fed and overnight-fasted conditions, with biological replicates (n = 3) for each group.

first: Seongjoon

last: Park

first: Sangeun

last: Kim

first: Hiroko

last: Hayashi

first: Isao

last: Shimokawa