title: Alkalinization of a Single Pair of Glial Cells Increases Lifespan, Health Span, and Stress Resistance in C. elegans

city: miami

first: Laura

last: Bianchi

state: FL

address: 1600 nw 10th ave

department: Physiology and Biophysics

institute: university of miami

summary: Aging depends on genetic and environmental factors, but the specific cell types and mechanisms that coordinate aging of the entire organism are not yet fully understood. Recent studies in C. elegans revealed that glial cells serve as upstream regulators of aging by conveying information about their stress status to other tissues. Glial cells regulate ionic homeostasis, which is essential for neuronal function and survival. Here we investigated the role of glial ion channel CLH-1, which is a glial pH regulator, in aging. We found that loss of clh-1 extends lifespan, improves stress resistance, reduces neuronal damage, and extends health span. These effects are linked to protective pathways, including those for oxidative stress and autophagy, and depend on pH regulation in glia.

overall_design: A single pool of approximately 2000 synchronized worms from wildtype(N2), clh-1, daf-16, daf-16;clh-1, and clh-1;Amsh clh-1 rescue strains was grown to Day 1 of adulthood. All samples were collected in three biological replicates. Pelleted worms were lysed using a pellet pestle motor (Kontes) in TRIzol reagent (Thermo Fisher, Waltham, MA). Total RNA was isolated with the Nucleospin RNA kit (Macherey-Nagel) following the manufacturer’s protocol. The quality of the mRNA was assessed using a NanoDrop 1000 v3.8 (Thermo Scientific), and samples containing 300 ng/µL of RNA with a volume of 20 µL were sent for next-generation RNA sequencing.

first: Lei

last: Wang

first: Enrique

last: Oliver

first: Dario

last: L D’Urso

first: Bianca

last: Graziano


title: Transcriptomic analysis of neuronal differentiation models of Kabuki Syndrome Type 1 [ChIP-Seq]

status: Public on Sep 11 2025

city: Manchester

first: Siddharth

last: Banka

address: Oxford Road

country: United Kingdom

institute: University of Manchester

type: Genome binding/occupancy profiling by high throughput sequencing

summary: Kabuki syndrome type 1 (KS1) is a neurodevelopmental disorder caused by loss-of-function variants in KMT2D which encodes a H3K4 methyltransferase. Here, we analysed transcriptomic differences across three stages of neuronal differentiation using patient-derived induced pluripotent stem cells (iPSCs). Overall, we identified hundreds of differentially expressed genes (DEGs) in iPSCs, NPs and CNs in KS1. We find that genes regulated by SUZ12, a subunit of Polycomb Repressive complex 2, are over-represented in KS1 DEGs at early stages of differentiation. We also identify loss of thousands of H3K4me1 peaks in iPSCs, neuronal progenitors (NPs) and early cortical neurons (CNs) in KS1. In conclusion, we present a disease-relevant human cellular model for KS1 that provides pathomechanistic insights of Kabuki Syndrome Type 1.

overall_design: RNASeq and H3K4me1 ChIPSeq profiling of iPSCs, Neuronal Progenitors and Cortical Neurons from Kabuki Syndrome Type 1 patients and controls.

first: Sara

last: Cuvertino

first: Evgenii

last: Martirosian

first: Peiwen

last: Cheng

first: Terence

last: Garner

first: Ian

middle: J

last: Donaldson

first: Adam

last: Jackson

last: Stevens

first: Andrew

middle: D

last: Sharrocks

first: Susan

last: Kimber


title: Transcriptomic and epigenomic analysis of neuronal differentiation models of Kabuki Syndrome Type 1 [RNA-Seq]

type: Expression profiling by high throughput sequencing


title: Gene expression profile of mouse diabetic kidney disease (DKD) injury

city: Wenzhou

first: shuxin

last: wang

state: Zhejiang

address: chashan

country: China

institute: wenzhou Medical University

summary: Diabetic kidney disease (DKD) is a significant clinical challenge, with an increasing prevalence. Our research identified that fibroblast growth factor 4 (FGF4) secreted by podocytes is a key factor in a mouse model of DKD. Given the importance of FGF4 in DKD-induced kidney injury, we performed gene expression analysis on kidney tissues. This analysis compared db/db model mice with those treated with recombinant FGF4 (rFGF4). The results showed that, compared to the db/db model group, db/db mice treated with long-term rFGF4 demonstrated significant improvements in renal function markers, such as serum urea nitrogen and urinary protein levels.Overall, our findings indicate that FGF4 is a critical regulatory factor in DKD-induced renal injury, providing evidence that it alleviates glomerular damage by inhibiting oxidative stress and apoptosis.

overall_design: To further investigate the role of FGF4 in kidney tissue, we established a diabetic kidney disease (DKD) model in db/db mice. The experiment was divided into two groups: the db/db model group and the rFGF4 treatment group. Subsequently, we performed gene expression profiling on the RNA-seq data from both groups.

first: Jie

last: Zhou

first: Shuxin


title: Single-cell RNA-sequencing of CD7 knockout CD8 T cells

city: Houston

first: William

last: Hudson

state: TX

address: 1 Baylor Plaza

department: Molecular and Cellular Biology

country: USA

institute: Baylor College of Medicine

summary: The goal of this study is to identify transcriptional changes in antigen-specific CD8 T cells caused by CD7 deletion.

overall_design: CD7-/- mice were crossed to CD45.1+ P14 mice, which have a transgenic TCR specific for gp33, an epitope of lymphocytic choriomeningitis virus (LCMV). CD7 knockout (KO) and littermate wildtype (WT) P14 cells were co-transferred to C57BL/6J mice, which were subsequently infected with 2e6 PFU of LCMV clone 13 following transient CD4 T cell depletion. >45 days after infection, WT and KO P14 cells were isolated from liver and spleens of infected animals, and naive P14 WT and KO cells were isolated from the blood of the donor mice. Individual cell types were labeled with hashing antibodies, pooled, and subjected to the 10x Genomics Chromium scRNA-seq workflow. Mouse hashing antibody sequences: Naive WT: Totalseq-C hash 1 (ACCCACCAGTAAGAC); Naive KO: Totalseq-C hash 2 (GGTCGAGAGCATTCA); Spleen WT P14s from infected mice: Totalseq-C hash 3 (CTTGCCGCATGTCAT); Spleen KO P14s from infected mice: Totalseq-C hash 4 (AAAGCATTCTTCACG); Liver WT P14s from infected mice: Totalseq-C hash 5 (CTTTGTCTTTGTGAG); Liver KO P14s from infected mice: Totalseq-C hash 6 (TATGCTGCCACGGTA)

first: Hudson

last: William

first: Hyslop

last: Sean


title: Bulk RNA-sequencing of CD7+ and CD7- CD8 T cells from chronic LCMV infection

summary: The goal of this study is to determine transcriptional differences between PD-1+ CD7 hi and PD-1+ CD7 low CD8 T cells during chronic viral infection.

overall_design: C57BL/6J mice were infected with 2e6 LCMV clone 13, delivered intravenously, after transient depletion of CD4 T cells with GK1.5 antibody. >45 days after infection, the indicated T cell populations were sorted from the spleens and livers of infected mice. Separately, naive CD8 T cells (CD44-CD62L+) were sorted from spleens of 3 uninfected mice. mRNA-sequencing libraries were made with the Takara SMART-seq mRNA kit.

first: Sean

last: Hyslop


title: Identification of epigenetic regulators of fibrotic transformation in cardiac fibroblasts through bulk and single-cell CRISPR screens

city: Salzburg

first: Wolfgang

last: Esser-Skala

address: Hellbrunner Strasse 34

country: Austria

institute: University of Salzburg

summary: Cardiac fibrosis is mediated by the persistent activity of myofibroblasts, which differentiate from resident cardiac fibroblasts in response to tissue damage and stress signals. The signaling pathways and transcription factors regulating fibrotic transformation have been thoroughly studied. By contrast, the roles of chromatin factors in fibroblast differentiation and their contribution to pathogenic cardiac fibrosis remain poorly understood. Here, we have combined bulk and single-cell CRISPR screens to characterize the roles of chromatin factors inex vivofibroblast differentiation. We uncover strong regulators of fibrotic states including Srcap and Tip60 chromatin remodelers, the NSL complex and the co-factors Hcfc1 and Wdr82. We confirm these factors are required for cellular processes underlying fibrosis including collagen synthesis and cell contractility. We use epigenetic profiling to demonstrate these chromatin factors facilitate the activity of pro-fibrotic transcription factors. Finally, using chemical perturbation in primary human cardiac fibroblasts we suggest Tip60 inhibition as a potential therapeutic approach for cardiac fibrosis.

overall_design:
Primary human cardiac fibroblasts were isolated from discarded tissue of two patients that underwent cardiac surgery and pre-treated with either Kat5 inhibitor or vehicle. Subsequently, their fibrotic responses after TGF-β stimulation were measured.

***************************************************************
Raw files for human/patient samples are being made available in EGA (https://www.ebi.ac.uk/ega/) for controlled access to the personally identifiable sequence data.
***************************************************************

first: Laura Pilar

last: Aguado-Alvaro

first: Nerea

last: Garitano

first: Judy

last: Sayers

first: Cynthia

last: del Valle

first: Daniel

last: Alameda-Serrano

first: Julen

last: Mendieta-Esteban

first: Maria Erendira

last: Calleja-Cervantes

first: Ainhoa

last: Goñi-Salaverri

first: Jon

last: Zazpe

first: Anna Rosaria

last: de Vito

first: Francesco

last: Marchese

first: Diego

last: Alignani

first: Juliana

last: Cudini

first: Torsten

last: Gross

first: Gregorio

last: Rábago

first: Nisha

last: Narayan

first: Laura

last: Martinez

first: Sonia

first: Brian

last: Huntly

first: Paul

last: Riley

first: Arantxa

last: Gonzalez-Miqueo

first: Jake P.

last: Taylor-King

first: Nikolaus

last: Fortelny

first: Beatriz

last: Pelacho

first: David

last: Lara-Astiaso


title: Effect of Early Diet on Gene Expression in Gastrointestinal Tract, Liver and Brain Regions of Neonatal Piglets

city: Davis, CA

first: Carolyn

middle: M.

last: Slupsky

address: One Shields Ave

department: Department of Nutrition, Department of food science and technology

institute: University of California, Davis

summary: We leveraged neonatal piglets as a preclinical model for human infants, with a system-level approach that integrates evidence from serum, urine, liver, brain and the gastrointestinal tract (GIT), with the bioactive function of α-lactalbumin, a rich source of tryptophan, in a formula feeding study. Complementing metabolomics data generated throughout the GIT during the early feeding period, we further integrated quantitative serum, liver, brain and urine metabolome data, as well as liver and brain transcriptome data to investigate the metabolic consequences behind the differential responses to diet. Transcriptional and metabolomics analysis revealed an individualized, divergent response to α-lactalbumin linked to either efficient utilization of tryptophan by the host, or production of indole-3-lactate by intestinal microbiota. This variability was further highlighted by differences in metabolic and immunological effects in a tissue-specific manner. Our work highlights the importance of considering the nutrition-microbiota-host metabolism axis to optimize the phenotypic response of a diet.

overall_design: 30 Piglets stayed with their sows for the first 5 days post-birth to consume colostrum. We conducted a feeding trial from postnatal day 6 to 16. On postnatal day 6, they were stratified by weight, sex, and litter and then randomly assigned to either continue with sow’s milk (SF reference group) or to start one of two piglet formulas: an α-lactalbumin enriched formula (ALAC group) or an formula cotaining α-lactalbumin reduced, whey protein isolate WPI formula (WPI group). We evaluated the gene expression profile of jejunum, ileum, colon, prefrontal cortex, striatum, hippocampus, hypothalamus and liver on postnatal day 16.

first: Xuan

last: He

first: Shannon

last: Shoff

middle: M


title: Impaired cAMP/CREB1 signaling drives mitochondrial dysfunction in skeletal muscle during cancer cachexia.

city: Novara

first: Francesco

last: Favero

state: NO

address: Corso Trieste 15/A

department: Translational Medicine - CAAD (Center for Translational Research on Autoimmune and Allergic Diseases)

country: Italy

institute: University of Eastern Piedmont

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

overall_design: Refer to individual Series


title: Impaired cAMP/CREB1 signaling drives mitochondrial dysfunction in skeletal muscle during cancer cachexia [ChIP-seq]

summary: Skeletal muscle wasting is a hallmark of cachexia, a cancer-associated syndrome that severely affects patients’ quality of life. Emerging evidence indicates that at early stages of cachexia a large transcriptional network of genes involved in mitochondrial biogenesis, dynamics, and function is down-regulated in skeletal muscle, thus leading to mitochondrial dysfunction and muscle wasting. Here, by exploiting in vivo and in vitro cachexia models, we report that i) tumor-induced impairment of cAMP/CREB1 signaling in skeletal muscle contributes to the downregulation of the transcriptional network sustaining mitochondrial function; ii) the cAMP-hydrolyzing phosphodiesterases 4D (PDE4D), whose transcript variants are deregulated in cachectic muscle, mediates tumor-induced cAMP signaling impairment in vitro. iii) boosting cAMP signaling by targeting PDE4 in vivo rescues mitochondrial-related gene expression, mitochondrial dysfunction, and mitigates muscle wasting. Collectively, we identified tumor-induced impairment of cAMP/CREB1 signaling as a driver of skeletal muscle mitochondrial dysfunction occurring during cancer cachexia.

overall_design: ChIP-seq profiling of phosphorylated CREB1 in gastrocnemius muscle from C26-injected and control mice.

first: Elia

last: Angelino

first: Lorenza

last: Bodo

first: Andrea

last: Lauria

first: Davide

last: Corà

first: Valentina

last: Proserpio

first: Giuseppina

last: Caretti

last: Graziani


title: Impaired cAMP/CREB1 signaling drives mitochondrial dysfunction in skeletal muscle during cancer cachexia [RNA-seq]

summary: 106 C26 murine adenocarcinoma cells in 100 μl of PBS were subcutaneously injected in the right flank of 2-month-old male Balb/c mice. Starting from day 4 post tumor inoculation, C26-bearing animals were injected intraperitoneally with rolipram (3 mg/kg) or vehicle (1,86% ethanol in saline). RNAseq was performed on gastrocnemius muscle from control (without tumor), C26 vehicle-treated, and rolipram-treated mice.

overall_design: Gene expression profile study of gastrocnemius muscle from mice injected with C26 adenocarcinoma cell line treated with vehicle (C26_veh) or rolipram (C26_rol), and healthy mice (ctr).


title: Cell-of-origin epigenome underlies SS18::SSX-mediated transformation [ChIP-seq]

city: Vancouver

first: Tully

middle: Michael

last: Underhill

state: British Columbia

address: 2222 Health Sciences Mall

department: Biomedical Research Centre

country: Canada

institute: University of British Columbia

summary: Synovial sarcoma is an aggressive soft-tissue malignancy that is characterized by a pathognomonic t(X;18)(p11.2;q11.2) translocation, which produces the fusion oncogene namedSS18::SSX. Despite recent advancements in our understanding of synovial sarcoma biology, the cell-of-origin remains undefined. A mesenchymal stromal cell (MSC) specific CreERT2 line was employed to expressSS18::SSXin fibroblasts and related cell types, resulting in 100% penetrant synovial sarcoma development in mice, with a median latency period of 16.2 ± 2.5 weeks. Murine tumours exhibited high concordance with human synovial sarcoma sub-types at the histological and molecular levels1. Genetic refinement of the cell-of-origin revealed that synovial sarcomas derive from a rareHic1+Pdgfra+Lgr5+fibroblastic population. Furthermore, longitudinal multi-omic profiling along the transformation continuum revealed the step-wise acquisition of a transformed phenotype initiated by the loss of a mature fibroblastic profile and subsequently, the gradual unmasking of an epigenetically embedded embryonic MSC program. Adult and embryonic MSCs exhibited overlapping H2AK119ub and H3K4me3/H3K27me3 (bivalent) histone marks, while SS18::SSX-mediated transformation culminated in the widespread loss of H3K27me3 at these genes and their consequent transcription. Collectively, these studies define a rare MSC context, conducive for SS18::SSX-mediated transformation, and demonstrate that SS tumorigenesis involves the induction and maintenance of an embryonic-like MSC phenotype.

overall_design: ChIP-Seq analysis using histone modifications H3K4me3, H3K27me3, H2AK119ub, H3K27ac, H3K4me3, H3K36me2, and H3K36me3 in adult (WT) and embryonic MSCs (E12.5) from Hic1;tdTom cells, and synovial sarcoma tongue tumor (tSRC) from Hic1;hSS2 cells.

first: Lesley

middle: A

last: Hill

first: R

middle: W

last: Scott

first: Lauren

last: Martin

first: Martin

last: Arostegui

first: George

last: Davenport

first: Marcos

last: Vemon

first: Jakob

last: Hofvander

first: Xue-Qi

last: Wang

first: Jinxiu

last: Li

first: Torsten

middle: O

last: Nielsen

first: Kevin

middle: B

last: Jones

last: Hirst

first: T


title: The fibroblast epigenome underlies SS18::SSX-mediated transformation in synovial sarcoma

summary: Synovial sarcoma (SyS) is an aggressive soft-tissue malignancy that is characterized by a pathognomonic t(X;18)(p11.2;q11.2) translocation, which produces the fusion oncogene named SS18::SSX. Despite recent advancements in our understanding of synovial sarcoma biology, the cell-of-origin remains undefined. Here we employ a mesenchymal stromal cell (MSC) specific CreERT2 line to express SS18::SSX in fibroblasts and related cell types, resulting in 100% penetrant synovial sarcoma development in mice, with a median latency period of 16.2 ± 2.8 weeks. Murine tumours exhibit high concordance with human synovial sarcoma subtypes at the histological and molecular levels1. Genetic refinement of the cell-of-origin reveal that synovial sarcomas derive from a rare Hic1+ Pdgfra+ Lgr5+ fibroblastic population. Furthermore, comparative transcriptomic analysis reveals the acquisition of a transformed phenotype initiated by the loss of a mature fibroblastic profile and subsequent unmasking of an epigenetically embedded embryonic MSC program. Adult and embryonic MSCs exhibite overlapping H2AK119ub and H3K4me3/H3K27me3 (bivalent) histone marks, while SS18::SSX-mediated transformation culminates in the widespread loss of H3K27me3 at these genes and their consequent transcription. Collectively, these studies define a rare MSC context, conducive for SS18::SSX-mediated transformation, and demonstrate that SyS tumorigenesis involves the induction and maintenance of an embryonic-like MSC phenotype.

overall_design: Control and synovial sarcoma cells collected from tongue, hindlimb muscle, stifle, and calvaria tissue were sequenced and analysed using scRNA-seq.

first: Xue Qi


overall_design: Control and synovial sarcoma cells collected from tongue, hindlimb muscle, and stifle tissue were sequenced and analysed using scATAC-seq.


title: Cellular responses during kidney normothermic machine perfusion reflect graft outcomes

status: Public on Sep 10 2025

city: Rotterdam

first: Hector

last: Tejeda Mora

address: Doctor Molewaterplein 40

department: Developmental Biology

country: Netherlands

institute: Erasmus MC

summary: There are currently no molecular tools that can reliably predict post-transplant outcome of kidney grafts during normothermic machine perfusion (NMP). In this study we investigated whether the cellular responses of donor kidneys during NMP can predict post-transplant outcome via transcriptomic analyses. Snap-frozen biopsies of 28 kidneys were taken before and after 2-hour NMP. 6 kidneys were included for single nucleus RNA sequencing (snRNA-seq) and 22 were for quantitative real-time PCR (qPCR). snRNA-seq analyses revealed a total of 38,451 cells distributed in 11 distinct cell types. NMP induced an upregulation of genes for ATP production-related proteins, heat shock proteins (HSP), transporter proteins and proteins that prevent protein misfolding. These findings were confirmed by the qPCR analyses. We observed no significant gene differences between the delayed graft function (DGF) and non-DGF kidneys. However, after NMP, the expression of HSP was above average in 3 kidneys with primary non-function (PNF) and kidneys that experienced acute rejection in the first month after transplantation compared to well-functioning kidneys. Overall, this study demonstrates that 2-hour NMP impacts gene expression profiles of the majority of cell types of the kidney. It suggests that NMP may serve to predict kidney function post-transplantation by triggering differential gene expression patterns.

overall_design: Snap-frozen biopsies from 6 kidneys taken before and after 2-hour NMP were subjected to snRNA-seq. Nuclei were isolated by nuclei isolation buffer (Nuclei EZ lysis buffer, N3408-200ML, Sigma-Aldrich). They were then loaded into the chromium controller (PN-120223, 10x Genomics) on a Chromium Next GEM Chip G (PN-2000177, 10x Genomics) and processed following the manufacturer’s original protocol. Data analysis was processed with Seurat (v4.2.0). Biopsies from another 22 kidneys taken at the same time points were included for qPCR to confirm the snRNA-seq data. Estimated glomerular filtration rates (eGFR) until 30 days post-transplant were used to determine post-transplant function.  2 discarded kidneys were collected as well for the control of "poor functional kidneys" .

first: Eric

last: Bindels

first: Shengbing


title: Benchmarking porcine pancreatic ductal organoids for drug screening applications

city: Oberschleissheim

first: Christos

last: Karampelias

address: Ingolstädter Landstraße 1

country: Germany

institute: Helmholtz Zentrum Munich

summary: Primary human pancreatic ductal organoids (HPDO) have emerged as a model to study pancreas biology and disease. Yet, donor material availability, and a lack of extensive benchmarking limits the range of applications. To address this gap, we established porcine pancreatic ductal organoids (PPDO) as a system from an easily obtainable source to model pancreatic ductal/progenitor biology. We benchmarked PPDO to HPDO and primary porcine pancreas using single-cell RNA sequencing (scRNA-Seq). We observed no overt phenotypic differences in PPDO derived from distinct developmental stages, with a WNT signaling enriched population characterizing PPDO. PPDO exhibited differentiation potential towards mature ductal cells and limited potential towards endocrine lineages. We used PPDO as a platform to assess the safety of FDA-approved drugs and showed conserved toxicity of statins and α-adrenergic receptor inhibitors between PPDO and HPDO cultures. Overall, our results highlight the PPDO as a model for mammalian duct/progenitor applications.

overall_design: The current repository contains all genomics datasets (bulk RNA-Seq and single-cell RNA-Seq) presented in the manuscript. Therefore here you can find a bulk RNA-Seq dataset from porcine pancreatic ductal organoids (PPDO) treated with an endocrine induction differentiation media and single-cell RNA sequencing datasets from two PPDO samples, one human pancreatic ductal organoid sample and two primary porcine pancreas datasets.  Raw fastq files have been uploaded to SRA database.

first: Kaiyuan

last: Yang

first: Falk

last: Farkas

first: Michael

last: Sterr

first: Mireia

middle: v

last: Den Bosch

first: Simone

last: Renner

first: Janina

last: Fuss

first: Christine

last: von Toerne

first: Soren

last: Franzenburg

first: Tatsuya

last: Kin

first: Eckhard

last: Wolf

first: Elisabeth

last: Kemter

first: Heiko

last: Lickert


title: Benchmarking porcine pancreatic ductal organoids for drug screening applications [bulkRNA-seq]


title: Benchmarking porcine pancreatic ductal organoids for drug screening applications [scRNA-seq]


title: Microglia-containing neural organoids as brain microphysiological systems for long-term culture

city: Baltimore

first: Lena

last: Smirnova

address: 615 N. Wolfe St

department: Environmental Health & Engineering

institute: Johns Hopkins University

summary: Microglia are cells essential for many aspects of brain development, homeostasis, and neuroinflammation that originate from the yolk sac during embryogenesis and migrate to the developing brain. Considering their developmental origin, many brain organoid models would naturally lack them and require a co-culture. We developed a microglia-integrated brain organoid model (immune-competent brain microphysiological system: µbMPS) using hiPSC-derived neural and microglia progenitors aggregated in U-bottom 96-well plates, enabling controlled and reproducible incorporation of microglia progenitors. We demonstrated that microglia integrated, matured, and survived long-term in the neural environment without costly exogenous microglia-specific growth factors and cytokines. We maintained microglia for over nine weeks, demonstrating functional activity, phagocytosis, and neuroinflammatory responses. µbMPS exhibited enhanced neuronal activity and maturity, offering a scalable, reproducible model for neurodevelopment, disease modeling, and neurotoxicology research.

overall_design: Human iPSC derived neuronal progenitor cells were combined with human iPSC derived immature microglia to form immune competent brain microphysiologic systems, that will mature to include functioning neurons, astrocytes, microglia and myelinating oligodendrocytes. Following two weeks of maturation the bMPS were collected for RNA sequencing to analyze expression of microglia related marker genes.

first: Alexandra

last: Rittenhouse

first: Caroline

last: Krall

first: Jesse

last: Plotkin

first: Dowlette-Mary

last: Alam El Din

first: Breanne

last: Kincaid

first: Jason

last: Laird


title: CTLA-4 Blockade Shifts the B Cell Repertoire Towards Autoimmunity

city: New Haven

first: Meng

last: Wang

state: CT

address: 300 George St

institute: Yale University

summary: Checkpoint inhibitors targeting CTLA-4 and PD-1 revolutionized the treatment of cancer patients but their use is limited by the emergence of immune-related adverse events (irAE). We assessed autoreactive B cell frequencies in the blood of cancer patients before and after treatment with checkpoint inhibitors by testing the reactivity of recombinant antibodies cloned from single B cells. We found that anti-PD-1 and anti-CTLA-4 combination therapy induced the emergence of autoreactive mature naïve B cells, whereas central B-cell tolerance remained functional. In contrast, anti-PD-1 alone did not alter autoreactive B cell counterselection. Anti-CTLA-4 injections in humanized mice also resulted in the production of autoreactive B cells, whereas anti-PD-1 did not. We conclude that CTLA-4 but not PD-1 is required for the removal of developing autoreactive mature naïve B cells and that CTLA-4 blockade broadens the peripheral B cell repertoire which likely contains clones that promote not only irAEs but also anti-tumor responses.

overall_design: Peripheral blood was collected from five melanoma patients at up to three time points: baseline (pre-treatment), ~6 weeks after two cycles of anti-CTLA-4 + anti-PD-1 combination therapy, and ~7 months while on anti-PD-1 monotherapy. From each draw, CD20⁺ B cells and CD4⁺ T cells were profiled using 10x Genomics Chromium 5′ single-cell gene expression and paired VDJ (BCR/TCR) libraries.

first: Elif

last: Çakan

first: Yile

last: Dai

first: Adrien

last: Mirouse

first: Delphine

last: Bouis

first: Joshua

last: Boeckers

first: Ruchi

last: Gera

first: Sally

last: Yraita

first: Leslie

last: Clapp

first: Ana Luisa

last: Perdigoto

first: Fabien

middle: R

last: Delmotte

first: Christopher

last: Massad

first: Antonietta

last: Bacchiocchi

first: Aaron

last: Ring

first: Yuval

last: Kluger

first: Harriet

first: Kevan

middle: C

last: Herold

first: Eric

last: Meffre


title: Divergent CNS–Peripheral Signaling Reflects Astrocyte Dysfunction and Contributes to Insulin Resistance in Early Aβ Pathology

city: Taichung City

first: Keng-Ying

last: Liao

address: No. 145, Xingda Rd., South Dist.,

department: Department of Veterinary Medicine

country: Taiwan

institute: National Chung Hsing University

summary: Alzheimer’s disease (AD) and type 2 diabetes mellitus (T2DM) are age-related disorders with similar pathological features, particularly insulin resistance and chronic inflammation. However, the primary drivers of insulin resistance in the AD brain remain debated. Although astrocytes and their metabolic functions have been increasingly implicated in AD, their specific role in brain insulin resistance is still unclear. In this study, we excluded peripheral metabolic confounders and focused on the alterations during a narrow time window surrounding amyloid-β (Aβ) plaque deposition in J20 mice. As Aβ pathology progressed, we observed a reduction in astrocyte numbers with increased morphological complexity. Furthermore, transcriptomic profiling demonstrated altered gene expression in synaptic, glial, and metabolic levels, along with a general suppression of insulin signaling pathways that indicated insulin resistance. Notably, we found a significant downregulation of serum and glucocorticoid-inducible kinase 1 (SGK1) and upregulation of insulin receptor substrate 2 (IRS2) expression, which diverged from the classic pattern observed in peripheral insulin resistance. We also detected a contradictory cytokine pattern in T-helper 17, where interleukin (IL)-6 and IL-17 levels were decreased in the hippocampus but elevated in the serum. This opposing trajectory suggest that astrocyte dysfunction and SGK1 downregulation have a critical role in immune signaling imbalance. Taken together, these findings highlight astrocyte depletion and/or dysfunction as key drivers of brain-specific insulin resistance and immune dysregulation in early AD, and that metabolic impairments in AD has a central nervous system-specific nature distinct from that in T2DM.

overall_design: RNA-seq profiling of the 15 weeks of age (pre-plaque stage) vurses 24 weeks of age (post-plaque) hAPP-J20 mice's hippocampus.

first: Yue-Loong

last: Hsin

first: Wei-Chi

last: Huang

first: Chun-Jung

last: Chen

first: Wen-Ying


title: Hepatocyte-specific MET deletion exacerbates acetaminophen-induced hepatotoxicity in mice

city: Pittsburgh

first: Shuchang

last: Liu

state: PA

address: 203 Lothrop Street

institute: University of Pittsburgh

summary: Despite the well-known role of MET in liver regeneration following partial-hepatectomy (PHx), its role in the clinically-relevant acetaminophen (APAP)-induced liver injury (AILI) model remains unexplored. AILI markedly differs from PHx because it is associated with massive liver necrosis. This study aims to delineate the role of MET specifically in AILI. Hepatocyte-specific MET-KO mice were given a toxic-dose of APAP and assessed for hepatotoxicity/regeneration parameters. MET deletion strikingly exacerbated initial hepatotoxicity and impaired subsequent proliferative response, culminating in significant mortality. Mechanistically, MET deletion enhanced JNK-activation and its mitochondrial translocation, resulting in excessive mitochondrial oxidative-damage, releasing cell-death inducer AIF into cytosol. Excess JNK-activation was attributed to reduced inhibitory activity of AKT on JNK in the absence of MET-signaling. Pharmacological activation of AKT reduced JNK-activation and hepatotoxicity in MET-KO mice. RNA-sequencing/immunoblotting not only showed repression of proliferative/survival signaling, but also activation of cell death/senescence pathways along with impaired unfolded-protein-response in MET-KO mice. Analysis of published single-nucleus RNA-sequencing data showed proliferation in livers from APAP-induced ALF patients was associated with strong activation of HGF/MET signaling in hepatocytes, with spatial-transcriptomics showing striking induction of HGF surrounding the necrotic-zones. Interestingly, 35% of the genes altered in human-ALF were regulated by MET in the mouse AILI-model. In conclusion, our study demonstrates that MET is crucial for restraining hepatotoxicity following APAP overdose via inhibiting mitochondrial cell-death signaling pathway.

overall_design: Wild-type and hepatocyte-specific MET knockout mice were given 300 mg/kg of Acetaminophen (APAP). Liver tissues were harvested at 0, 6, and 24hr post-APAP overdose.

first: Siddhi

last: Jain

first: Ranjan

last: Mukherjee

first: Gillian

last: Williams

first: Liu

last: Jia-Jun

first: Lanuza

last: Faccioli

first: Zhiping

last: Hu

first: Rodrigo

last: Florentino

first: Alejandro

last: Soto-Gutierrez

first: George

middle: K

last: Michalopoulos

first: Silvia

first: Joseph

last: Locker

first: Bharat

last: Bhushan


title: Neuronal-Activity Dependent Mechanisms of Small Cell Lung Cancer Pathogenesis

city: New York

first: Karan

last: Luthria

state: New York

address: 650 W 168th Street

department: Medicine

institute: Columbia University Vagelos College of Physicians and Surgeons

summary: Neural activity is increasingly recognized as a crucial regulator of cancer growth. In the brain, neuronal activity robustly influences glioma growth both through paracrine mechanisms and through electrochemical integration of malignant cells into neural circuitry via neuron-to-glioma synapses. Outside of the CNS, innervation of tumors such as prostate, breast, pancreatic and gastrointestinal cancers by peripheral nerves similarly regulates cancer progression. However, the extent to which the nervous system regulates small cell lung cancer progression, either in the lung or when growing within the brain, is less well understood. Small cell lung cancer (SCLC) is a lethal high-grade neuroendocrine tumor that exhibits a strong propensity to metastasize to the brain. Here we demonstrate that SCLC cells in the brain co-opt neuronal activity-regulated mechanisms to stimulate growth and progression. In the lung, vagus nerve transection markedly inhibits primary lung tumor formation and development, highlighting a critical role for innervation in SCLC growth. In the brain, glutamatergic and GABAergic cortical neuronal activity each drive proliferation of SCLC in the brain through both paracrine and synaptic neuron-cancer interactions. SCLC cells form bona fide neuron-to-SCLC synapses and exhibit depolarizing currents with consequent calcium transients in response to neuronal activity. SCLC cell membrane depolarization is sufficient to promote the growth of intracranial tumors. Taken together, these studies illustrate that neuronal activity plays a crucial role in dictating SCLC pathogenesis in both the lung and the brain.

overall_design:
A range of 1.0 – 1.4 × 10⁴ nuclei per reaction were loaded onto a Chromium Controller (10x Genomics) using Single Cell 5′ Reagent Kits v2 (10x Genomics Cat# 1000263). Nuclei were suspended in ST buffer without RNase inhibitor prior to loading. Following reverse transcription and bead cleanup, cDNA amplification was performed with one additional PCR cycle compared to the standard protocol to compensate for the reduced RNA content in nuclei relative to whole cells.

***************************************************************
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.
***************************************************************

first: Benjamin

last: Izar

first: Humsa

last: Venkatesh

first: Solomiia

last: Savchuk


title: RfaH is Essential for Virulence and Adaptive Responses in Yersinia pseudotuberculosis Infection

city: Umeå

first: Joram

last: Waititu

address: 67 umea

country: Sweden

institute: Umeå University

summary: We previously suggested that increased expression of the gene encoding transcriptional antiterminator RfaH during Yersinia pseudotuberculosis transcriptional reprogramming is necessary for adapting to persistent infection. In this study, we examined the role of RfaH in virulence and bacterial physiology under infection-relevant stress conditions, and identified genes differentially regulated in the absence of RfaH in Y. pseudotuberculosis. We employed a mouse infection model and phenotypic assays to test RfaH's role in virulence and physiology, as well as RNA sequencing, including O-antigen biosynthesis-deficient strains. Our findings demonstrate that loss of RfaH significantly attenuates virulence, reducing the capacity of Y. pseudotuberculosis to establish persistent infection. RfaH expression is increased during the stationary growth phase and under various stress conditions, such as high osmolarity and bile salts, which are known to induce envelope stress. Functional assays revealed that the ΔrfaH strain displayed defects in motility and increased clumping, indicating altered surface properties affecting motility. Moreover, transcriptomic profiling of the ΔrfaH strain revealed a specific RfaH-dependent gene set after filtering out genes affected by O-antigen-related mutations, thereby minimizing confounding effects from surface structure alterations. These results suggest that RfaH influences a broader set of virulence and adaptation pathways beyond O-antigen regulation.  Collectively, our findings suggest that RfaH is essential for the virulence and adaptive capacity of Y. pseudotuberculosis to colonize the host. This study provides insights into regulatory mechanisms that facilitate bacterial survival in hostile environments and highlights the importance of RfaH and its regulatory targets in the pathogenesis of Y. pseudotuberculosis.

overall_design:
We performed phenotypic assays to dissect RfaH-dependent changes during bacterial growth and establishment of persistent infection in the host.
We performed massive parallel sequencing of various mutants (ΔrfaH, m-ops, and ΔO-aB) and the wild-type (wt) strain at control (26°C) and temperature treatment (37°C) on the Illumina MiSeq sequencing platform to offer an in-depth transcriptome scenario of Y. pseudotuberculosis in response to environmental stress.
The transcriptome data obtained was then used to pinpoint common as well as specific mutation related genes and pathways that may shed more light on the potential molecular mechanisms of RfaH in Y. pseudotuberculosis persistent infection

first: Kristina

last: Nilsson

first: Gerald

last: Maumus

first: Tiago

last: Costa

first: Kemal

last: Avican


title: Circulating nucleic acids in plasma of individuals with human lymphatic filariasis

city: Bethesda

first: Sasisekhar

last: Bennuru

state: MD

address: 10 Center Dr, Bldg 10, Rm 11N208

department: LPD

institute: NIH/NIAID

summary: Circulating nucleic acids (RNA / DNA) found in body fluids have been shown to be good biomarkers for diagnosis of infections. The short half life of nucleic acids makes them ideal choice for detecting active infections and hence good targets for molecular testing.

overall_design: Plasma RNAseq was performed on total RNA extracted from plasma of W. bancrofti infected individuals from India and Cook Islands. Plasma of healthy un-infected blood bank volunteers were used as controls.


title: Gene expression data for keratinocyte grown on different substrates

city: Nedlands

first: Chee Wai

last: Wong

state: WA

address: Northern Entrance, Perth Children's Hospital, 15 Hospital Ave

country: Australia

institute: Telethon Kids Institute

summary: The study performed whole genome microarray gene expression profiling on primary human keratinoctyes cultured on collagen I, adult dermal fibroblast-derived ECM or foetal dermal fibroblast-derived ECM.  Our gene array data showed that primary human keratinocytes grown on foetal dermal ECM upregulated genes involved in cell cycle, whereas on adult dermal ECM, a mix of differentiation and cell cycle genes were upregulated.

overall_design: Primary human keratinocytes were cultured on collagen I, adult dermal fibroblast-derived ECM or foetal dermal fibroblast-derived ECM for RNA extraction and hybridization on Affymetrix microarrays.

first: Chee-Wai

first: Deirdre

last: Coombe


title: Transcriptome analysis of Streptococcus mutans biofilm cells deficient in the DpnII restriction-modification system

city: Toronto

first: Delphine

last: Dufour

state: Ontario

address: 124 Edward Street

institute: Faculty of Dentistry, University of Toronto

summary: Human pathogens use cell-cell communication systems, quorum sensing, to regulate virulence factors. Our recent work aiming at deciphering the quorum sensing regulon of Streptococcus mutans, a caries pathogen, revealed a locus encoding an atypical type II restriction-modification (R-M) system, DpnII, comprising two adenine methyltransferases. A recent survey of bacterial genomes demonstrated the widespread occurrence of methylated DNA, and the importance of DNA methylation was highlighted by the diverse processes in which they function. The present study aimed at deciphering the role of DNA methylation during S. mutans biofilm formation. A mutant strain, deficient in the DpnII R-M locus composed of the SMU.504 and SMU.505 genes encoding the two adenine methyltransferases and the SMU.506 gene encoding the DpnII restriction enzyme, was constructed in S. mutans wild-type (WT) strain. Transcriptome analysis was then performed to evaluate the differential biofilm gene expression between the WT cells and the DpnII R-M deficient cells.

overall_design: Biofilms were developped in BHI broth complemented with 1% (w/v) sucrose for 6 hours at 37°C in the presence of 5% CO2.  The gene expression profiling of the DpnII R-M biofilm mutant cells was compared to the one of the WT biofilm cells.

first: Haowei

last: Zhao

first: Celine

last: Levesque


title: The cancer-specific lncRNA LISR customizes ribosomes to suppress antitumour immunity

city: Leuven

first: Eleonora

last: Leucci

address: Herestraat 49, bus 818 room 06.423

department: Oncology

country: Belgium

institute: KU Leuven

summary: We report the changes in translatome of a  melanoma line upon knock down of LISR

overall_design: The ribosome-bound RNAs of a melanoma line transfected with siLISR or siControl were compared

first: Sonia

last: Cinque

first: Yvessa

last: Verheyden


title: The stroke risk gene Foxf2 maintains brain endothelial cell function via Tie2 signaling

city: Planegg-Martinsried

first: Filippo M.

last: Cernilogar

address: Grosshaderner Strasse 9

department: Biomedical Center

institute: LMU Munich

summary: Stroke is a leading cause of death and long-term disability. In up to 30% of cases the underlying etiology is cerebral small vessel disease (SVD), the mechanisms of which are insufficiently understood. Genome-wide association studies have identified FOXF2 as a major risk gene for SVD and stroke. Foxf2 encodes a transcription factor that in the brain is primarily expressed in endothelial cells (ECs) and pericytes but the mechanisms linking Foxf2 to cerebrovascular disease are unknown. Here we show that Foxf2 maintains EC function via Tie2 signaling and limits infarct size in mice after middle cerebral artery occlusion. EC-specific inactivation of Foxf2 in adult mice resulted in blood-brain barrier leakage, which was exacerbated after experimental stroke compared to controls. Proteomic analyses of brain ECs from Foxf2 deficient mice as well as human pluripotent stem cell (iPSC) derived ECs lacking FOXF2 revealed a downregulation of multiple proteins involved in Tie2 signaling. We further found that endothelial Foxf2 deficiency compromises functional hyperemia, reduces endothelial NO production, and increases the size of experimentally induced infarcts via Tie2 signaling. Pharmacological treatment with the Tie2 activator AKB-9778 rescued the effects of Foxf2 deficiency on key outcomes. Moreover, RNA sequencing in combination with chromatin immunoprecipitation and sequencing in ECs revealed that FOXF2 functions as a transcriptional activator of Tie2 and other endothelial lineage-specific genes. Collectively, our results highlight the role of endothelial dysfunction and of reduced Tie2 signaling in SVD and stroke, thus offering new perspectives for therapeutic interventions.

overall_design: Foxf2 ChIPseq in  endothelial  cells

first: Filippo

first: Judit

last: González-Gallego

first: Martin

last: Dichgans

first: Gunnar

last: Schotta


title: Cell-of-origin epigenome underlies SS18::SSX-mediated transformation [RNA-seq]

first: Tully

last: Underhill

overall_design: Transcriptome wide profiling of wt tongue samples, tongue tumors and sorted cells from embryonic age 12.5 mouse embryos (Hic1+ MSC population)

first: Lesley

last: Hill

first: R

last: Scott

first: Lauren

last: Martin

last: Arostegui

first: George

last: Davenport

first: Marcos

last: Vemon

first: Jakob

last: Hofvander

first: Xue-Qi

last: Wang

first: Jinxiu

last: Li

first: Torsten

last: Nielsen

first: Kevin

last: Jones

last: Hirst

first: T


title: Synapse-centered novel omics targets in Alzheimer’s disease - miRNA

city: El Paso

first: Enrique

middle: Ivan

last: Ramos

state: Texas

address: 5001 El Paso Dr.

department: Molecular and Translational Medicine

institute: Texas Tech University Health Sciences Center El Paso

type: Non-coding RNA profiling by high throughput sequencing

summary: Synapse dysfunction is an early event of Alzheimer’s disease (AD). It is caused by multiple cellular and pathological factors such as Amyloid beta, p-tau, inflammation, and aging. However, the exact molecular mechanism of synapse dysfunction in AD is largely unknown. Therefore, to understand the molecular basis of synapse dysfunction in AD, we conducted a high throughput multi-omics analysis of the synaptosome fraction in postmortem brain samples from AD patients and cognitively normal individuals. First, microRNA and mRNA HiSeq analysis were performed on the synaptosomes extracted from the postmortem brains of unaffected control (UC) individuals and AD patients. Next, we conducted the mass spectrometry analysis of synaptosomal proteins in the same sample group of HC and AD. The transcriptomic and proteomic profiling of synaptosome showed the significant deregulation of miRNA, mRNA and protein signatures in AD vs HC.  Further, we used an integrated transcriptomic and proteomic approach to understand the molecular interactions of deregulated synapse miRNAs, mRNAs, and proteins in the same samples of AD and HC. Multi-omics integration analysis of synapse miRNAs-mRNAs-proteins revealed the involvement of omics targets in several biological processes and molecular functions such as signal transduction, protein binding, GABAergic synapse, and synaptic vesicle cycle, etc. Our study unveiled synapse-centered novel omics candidates that could be potential therapeutic targets to restore synapse dysfunction in AD.

overall_design: We used postmortem brains from AD (n=42) and controls (n=14). Synaptosomes were isolated from AD and control brains. Further, total RNA were isolated from the synaptosome and subjected to miRNA and mRNA HiSeq analysis.

first: Axel

last: Hidalgo

first: Shrikanth

last: Gadad

first: Subodh

last: Kumar

first: Bhupender

last: Sharma

first: Daniela

last: Rodarte

first: Davin

last: Devara


title: Synthetic mimics of wound-induced carrot microRNAs affect lipid metabolism in cultured adipocytes

status: Public on Sep 09 2025

city: Monterrey

first: Edwin

last: Reza

state: Nuevo Leon

address: ve. Ignacio Morones Prieto 3000

department: Escuela de Medicina y Ciencias de la Salud

country: Mexico

institute: Tec de Monterrey

summary: Background/Objectives: Plant-derived microRNAs (miRNAs) have emerged as cross-kingdom regulatory molecules, but their capacity to influence mammalian metabolism is still poorly understood. This study aimed to investigate whether miRNAs induced in carrots (Daucus carota) by postharvest wounding stress can modulate adipocyte lipid accumulation. Methods: High-throughput small RNA sequencing was performed to identify stress-responsive miRNAs in wounded carrots. Bioinformatic analyses predicted potential mammalian targets, focusing on genes involved in adipogenesis and lipid regulation, including those in the insulin and FoxO signaling pathways. Selected miRNAs were functionally validated in 3T3-L1 adipocytes by assessing intracellular triglyceride levels and glycerol release. Results: Six stress-responsive carrot miRNAs were predicted to target mammalian lipid metabolism genes. Functional assays revealed that miR165a-3p, miR232a-5p, and miR1799 significantly decreased intracellular triglyceride accumulation and increased glycerol release, suggesting enhanced lipolysis. These effects support the potential regulation of adipocyte metabolism through plant miRNA mimics. Conclusions: Our findings provide experimental evidence for stress-induced carrot miRNAs mimics potentially modulate fat accumulation. This work expands current understanding of dietary plant miRNAs and highlights their potential role as functional food components for metabolic health improvement. Further research is needed to establish their gastrointestinal stability, uptake from dietary matrices, and in vivo effects.

overall_design: small RNA-seq profiling of Daucus carota at time 0, 24 and 48 hours (T0, T24 and T48) of wounding stress application and storage.

first: Reza-Zaldivar

last: Edwin E.

first: Jacobo-Velázquez

last: Daniel A.


title: Prediction and Characterization of Genetically-Regulated Expression of Asthma Tissues from African-Ancestry Populations

city: Aurora

first: Randi

last: Johnson

state: Colorado

address: 1890 N. Revere Court

institute: University of Colorado

summary:
Background: Genetic control of gene expression in asthma-related tissues is not well-characterized, particularly for African-ancestry populations, limiting advancement in our understanding of the increased prevalence and severity of asthma in those populations.
Objective: To create novel transcriptome prediction models for asthma tissues (nasal epithelium and CD4+ T cells) and apply them in transcriptome-wide association study to discover candidate asthma genes.
Methods: We developed and validated gene expression prediction databases for unstimulated CD4+ T cells and nasal epithelium using an elastic net framework. Combining these with existing prediction databases (N=51), we performed TWAS of 9,284 individuals of African-ancestry to identify tissue-specific and cross-tissue candidate genes for asthma.
Results: Novel databases for CD4+ T cells and nasal epithelial gene expression prediction contain 8,351 and 10,296 genes, respectively, including four asthma loci (SCGB1A1, MUC5AC, ZNF366, LTC4S) not predictable with existing public databases. Prediction performance was comparable to existing databases and was most accurate for populations sharing ancestry with the training set (e.g. African ancestry). From transcriptome-wide association study, we identified 17 candidate causal asthma genes (adjusted P<0.1), including genes with tissue-specific (IL33 in nasal epithelium) and cross-tissue (CCNC and FBXW7) effects.
Conclusions: Expression of IL33, CCNC, and FBXW7 may affect asthma risk in African ancestry populations by mediating inflammatory responses. The addition of CD4+ T cell and nasal epithelium prediction databases to the public sphere will improve ancestry representation and power to detect novel gene-trait associations from transcriptome-wide association study.

overall_design: RNA-Seq of homo sapiens: CD4+ T cells

first: Sarah

last: Slack

first: Erika

last: Esquinca

first: Christopher

middle: H

last: Arehart

first: Meher Preethi

last: Boorgula

first: Brooke

last: Szczesny

first: Alex

last: Romero

first: Monica

last: Campbell

first: Sameer

last: Chavan

first: Nicholas

last: Rafaels

first: Harold

last: Watson

first: R Clive

last: Landis

first: Nadia

middle: N

last: Hansel

first: Charles

last: Rotimi

last: Olopade

first: Camila

last: Figueiredo

first: Carole

last: Ober

first: Andrew

last: Liu

first: Eimear

middle: E

last: Kenny

first: Kai

last: Kammers

first: Ingo

last: Ruczinski

first: Margaret

last: Taub

first: Michelle

last: Daya

last: Gignoux

first: Katerina

last: Kechris

first: Kathleen

last: Barnes

first: Rasika

last: Mathias


title: Biomarkers of Immune Dysregulation and Post-Treatment Inflammation in Spinal Muscular Atrophy

city: Atlanta

first: Manoj

last: Bhasin

state: GA

address: 1750 Haygood Dr NE, N320

department: Aflac Cancer and Blood Disorders Center

institute: Children's Healthcare of Atlanta

summary: Spinal Muscular Atrophy (SMA) is a neurodegenerative disorder primarily affecting motor neurons, but immune dysfunction may contribute to disease progression and treatment response. While AAV9-delivered SMN1 gene therapy (e.g., Zolgensma) improves survival, long-term motor outcomes remain variable. This study integrates bulk and single-cell RNA sequencing (scRNA-seq) to define immune dysregulation in SMA. We analyzed peripheral blood from infants with SMA (n = 7 for bulk RNA-seq; n = 4 for scRNA-seq, <25 mo of age) along with age-matched healthy controls (n = 4 for bulk RNA-seq; n = 6 for scRNA-seq). We profiled differentially expressed genes, immune pathways, cell–cell interactions, and gene regulatory networks.  SMA samples showed distinct transcriptomic signatures and elevated immune activation compared to controls. NECTIN1 was identified as a transcriptomic biomarker of disease progression, while HSPA7 was validated from prior reports. A 6- to 7-mo inflection point marked a transition from metabolic regulation to immune activation in SMA infants. NF-κB–related inflammatory gene expression was significantly elevated post–gene therapy relative to both pretreatment and healthy controls, with IL1B and RNF19B emerging as key transcriptomic mediators. scRNA-seq revealed early dysfunction and G1-phase arrest in CD4+ T-cells, along with a switch to RELB-mediated noncanonical NF-κB signaling. In symptomatic infants, CD8+ T-cells showed higher proliferation and exhaustion, with co-upregulation of TBX21 and EOMES, genes consistent with chronic stimulation and a trajectory toward terminal differentiation. Immune dysregulation is a central feature of SMA and may influence treatment response. These findings support future development of adjunct immunomodulatory strategies to enhance gene therapy efficacy and suggest that immune signatures may correlate with motor function outcomes.

overall_design: Bulk RNA-seq profiling of peripheral blood samples from infants with spinal muscular atrophy before and after gene therapy and disease-modifying treatments. Single-cell RNA-seq profiling of peripheral blood samples from infants with spinal muscular atrophy, both presymptomatic and symptomatic.

first: Sean

last: Jordan

first: Mojtaba

last: Bakhtiari

first: Swati

middle: S

first: Sumit

last: Verma


title: Identification of Pre-Disease State in NC/Nga Mice with Atopic dermatitis-like Symptoms using Dynamical Network Biomarkers

city: shimogyo-ku

first: Tomohiro

last: Sensui

address: chudoji, awatacho

country: Japan

institute: Maruho

summary: Atopic dermatitis (AD) is a common skin disease worldwide that is characterized by itchy eczema that undergoes cycles of exacerbation and remission. Although several biomarkers reflect AD severity, reliable markers for predicting disease onset and recurrence remain unclear. The dynamical network biomarker theory detects pre-disease states or pre-symptomatic states by analyzing characteristic network fluctuations just before phase transitions from healthy states to disease states. To investigate the applicability of dynamical network biomarker theory to AD, we conducted blood transcriptome analysis in NC/Nga mice before and after the onset of AD-like dermatitis. We identified 356 dynamical network biomarker genes whose temporal fluctuations enabled the detection of the pre-disease state preceding AD-like dermatitis onset. These genes were significantly enriched in pathways related to endoplasmic reticulum stress and apoptosis; fluctuations in these pathways may be associated with the onset of AD. Our study indicates that the dynamical network biomarker theory may be applicable to AD and that identifying a pre-disease state may enable early intervention and disease prevention. Collectively, this approach could provide valuable insights into maintaining long-term remission and improving AD management strategies.

overall_design: To investigate the characteristics of the transcriptome before and after AD-like dermatitis onset, as well as according to the severity of the AD-like dermatitis, the transcriptome of whole blood from NC/Nga mice was obtained at various time points.


title: Mechanoresponsive genomic enhancers potentiate the cellular response to matrix stiffness [hicar]

city: Durham

first: Charles

last: Gersbach

state: North Carolina

address: 101 science drive rm 2323

institute: Duke University

summary: Epigenetic control of gene regulation and cell phenotype is influenced by changes in the mechanical microenvironment. Yet how mechanical forces precisely influence epigenetic state to regulate transcriptional responses remains largely unmapped. Here, we combine genome-wide epigenome profiling, epigenome editing, and phenotypic and single-cell RNA-seq screening to identify a sub-class of genomic enhancers that is responsive to the mechanical microenvironment. These enhancers regulate genes that act as key drivers for a variety of functional behaviors including apoptosis, mechanotransduction, proliferation, and migration. We find distinct patterns wherein subsets of mechano-enhancers can be preferentially active on either soft or stiff extracellular matrix (ECM) contexts. Epigenetic editing of these mechano-enhancers on rigid materials precisely tunes mechanically-induced gene expression to levels observed on softer materials, and broadly enables reprogramming of cellular response to the mechanical microenvironment. These mechanically-activated enhancers act as key signal transducers and may constitute a new class of targets that can be modulated to alter mechanically-driven disease states.

overall_design: To investigate if mechanical stimuli altered 3-D chromatin interactions, we performed HiCAR (Hi-C on accessible regulatory DNA) on HFF cells cultured on either soft (1 kPa) or stiff (50 kPa) hydrogels

first: Cosgrove

last: Brian D.

first: Bounds

last: Lexi. R.

first: Key Taylor

last: Carson

first: Su

last: Alan L.

first: Rizzo

last: Anthony J.

first: Barrera

last: Alejandro

first: Crawford

last: Gregory .E.

first: Hoffman

last: Brenton D.

first: Gersbach

last: Charles A.


title: Red blood cell-mediated enhancement of hematopoietic stem cell functions via Hes1-dependent pathway

city: Suita

first: Daisuke

last: Motooka

state: Osaka

address: 3-1, Yamadaoka

institute: NGS core facility, Research Institute for Microbial Diseases, Osaka University

summary: In bone marrow the number of cells is balanced between production and loss. After chemotherapy, blood cell counts initially drop but later recover as hematopoietic progenitor cells expand, although the mechanisms behind this recovery were still elusive. The study investigates how red blood cells (RBCs) influence hematopoietic stem cell (HSC) function during bone marrow recovery. Following chemotherapy, RBC concentration in bone marrow peaked on the 5th day post-treatment, coinciding with the recovery of hematopoiesis. Co-culturing HSCs with RBCs resulted in a significant increase in hematopoiesis, preferentially differentiating into myeloid lineage cells. Direct contact between RBCs and HSCs is essential for the hematopoietic enhancement, and HSCs pre-cultured with RBCs showed higher levels of donor-derived mature hematopoietic cells after transplantation. RNA sequencing identified Hes1 being the most significantly upregulated transcription factor in RBC co-culture and Hes1-deficient HSCs showed a reduced response to RBC-induced hematopoiesis. These findings highlight the importance of RBCs and Hes1 in enhancing hematopoietic recovery following bone marrow stress.

overall_design: To identify the molecular basis responsible for the RBC-induced enhancement of hematopoietic function of hematopoetic stem cells, we compared gene profiling of hematopoetic stem cells (LT-HSC and LSK) cultured in the presence or absence of RBCs.

first: Erika

last: Yamashita

first: Soichiro

last: Hashimoto

last: Okuzaki

first: Takao

last: Sudo

first: Masaru

last: Ishii


title: NSUN2 promotes leukemogenesis by FTH1-mediated anti-ferroptosis and FBL-mediated ribosome biogenesis in B-ALL

city: wenzhou

first: bin

last: zhou

address: Nanbaixiang, Ouhai District, Wenzhou, Zhejiang Province

institute: Affiliated Hospital of Weifang Medical University

summary: NOP2/Sun RNA methyltransferase family member 2 (NSUN2) catalyzes 5-methylcytosine (m5C) modifications in tRNA, rRNA, and mRNA, playing critical roles in various malignancies. However, its expression and functional relevance in B-acute lymphoblastic leukemia (B-ALL) remain largely undefined. Lineage-negative progenitor cells from Nsun2 knockout (Δ/Δ) and wild-type (fl/fl) mice were used to generate BCR-ABL (P190)-driven murine B-ALL model. Furthermore, RNA sequencing (RNA-seq) was performed to identify NSUN2 targets. Here, we found that NSUN2 expression was significantly higher in bone marrow (BM) cells from B-ALL patients than normal controls (NCs). Knockdown of NSUN2 reduced m5C amounts, induced apoptosis and ferroptosis in B-ALL cells. Moreover, Nsun2 knockout significantly suppressed the leukemic burden and extended the OS in murine B-ALL model in vivo. RNA-seq and subsequent studies identified ferritin heavy chain 1 (FTH1) as a downstream target of NSUN2. Mechanistically, NSUN2 knockdown reduced m5C modifications on 3'UTR of FTH1 mRNA, impairing its stability and reducing FTH1 expression. Overexpression of wild-type (WT) NSUN2, but not its mutants, blocked NSUN2 knockdown-induced cytotoxic effects, indicating that NSUN2 enhances leukemogenesis in an m5C-dependent manner. In addition, NSUN2 facilitated global protein synthesis and ribosome biogenesis by enhancing fibrillarin (FBL) translation efficiency. In contrast, Nsun2 depletion was dispensable for hematopoiesis and exerted minimal impact on ferroptosis and protein synthesis in murine pre-B (B220+) cells, suggesting selective leukemic dependency. Our results demonstrate that NSUN2 facilitates leukemogenesis by increasing FTH1 expression and enhancing FBL-mediated ribosome biogenesis in an m5C-dependent manner. Targeting NSUN2 might provide a promising therapeutic strategy for B-ALL.

overall_design: we established Mus musculus stem cell in which each target gene has been knocked down by shRNA.We then performed gene expression profiling analysis using data obtained from RNA-seq .Comparative gene expression profiling analysis of RNA-seq data for NELM-6 cells and its KD derivatives (shNUSN2).

first: Yigang

last: Yuan

first: Xuanyu

last: Yu

first: Min

last: Li

first: Chen

last: Meng

first: Xiaofei

last: He

first: Shanshan

last: Wu

first: Yaqian

last: Qin

first: BIN

last: ZHOU

first: Shenmeng

last: Gao


title: Pseudouridylation of 7SK by PUS7 regulates Pol II transcription elongation

city: Chicago

first: Chuan

state: IL

address: 929 E 57th St

department: Chemistry Department

institute: University of Chicago

summary: Pseudouridine (Ψ) is a widespread RNA modification in various RNA species, including rRNA, tRNA, snRNA and mRNA. Ψ plays a crucial role in RNA metabolism, where it regulates pre-mRNA splicing and affects protein translation. Whether and how Ψ may regulate transcription have not be adequately studied. Here, we report that pseudorudine synthase 7 (PUS7) can mediate pseudouridylation of 7SK small nuclear RNA (snRNA), a regulator of RNA polymerase II (Pol II) promoter-proximal pausing. PUS7 loss leads to hypo-pseudouridylation and facilitates sequestration of the positive transcription elongation factor b (P-TEFb) complex from 7SK. The release of P-TEFb from 7SK increases serine 2 phosphorylation (Ser2P) in the RNA Pol II C-terminal domain and enhances transcription elongation. In colorectal cancer (CRC) cells, the Ψ level of 7SK could be modulated by PUS7, or by site-specifically targeted pseudouridylation through dCas13b-guided system. Hypo-pseudouridylation on 7SK with PUS7 depletion promotes KLF6/DDIT3-mediated cell apoptosis and sensitizes CRC cells to 5-FU.

overall_design: We performed BID-seq, PAR-CLIP, KAS-seq and mRNA-seq to study the role PUS7 plays in transcription process. BID-seq, PAR-CLIP and mRNA-seq showed 7SK is the key substrate of PUS7. KAS-seq indicated that PUS7 regulates transcrition elongation process by tuning the pseudouridylation of 7SK.

first: Zhao

last: Yutao

first: He

last: Chuan


title: Nuclear respiratory factor 1(NRF1) sustains the development, progression and resistance of Multiple Myeloma [RNA-Seq]

city: Rome

first: Maurizio

last: Fanciulli

address: Via Elio Chianesi 53

department: Department of Research, Advanced Diagnostic, and Technological Innovation

institute: IRCCS Regina Elena National Cancer Institute

summary: Multiple myeloma (MM) is a hematological malignancy characterized by the clonal proliferation of plasma cells within the bone marrow. Despite significant advancements in understanding the pathogenesis and the development of novel therapeutic approaches, MM remains incurable. Emerging evidence indicates aberrant epigenetic activity at cis-regulatory elements (CREs). However, the characterization of these events and the definition of relative impact with MM phenotype is only partially known. To address this gap, we comprehensively analyzed the epigenetic changes occurring during MM progression to identify the events and the key transcriptional regulators sustaining the disease.We profiled a cohort of 55 patient MM samples at diagnosis, post-therapy, and relapse and a cohort of 16 MGUS samples using ATAC-seq. Then, we used footprinting analysis to identify detailed changes in transcription factor engagement. We conducted experiments using in vitro and in vivo methods, including primary cell line models and a MM mouse model (vk-Myc). We employed high-throughput techniques such as ChIP-seq, RNA-seq, and RNA-Single Cell. Our results were confirmed using shRNA interference, dCas9-KRAB-Mediated interference, and the usage of an independent cohort.We stratified the pervasiveness of open chromatin loci in our MM cohort. Penetrant loci were enriched for the binding of the Nuclear Respiratory Factor 1 (NRF1) in MM but not in MGUS samples. These findings were validated using 144 published ATAC-seq profiles of MM. ChIP-seq analysis on 15 MM and 6 MGUS patients confirmed that NRF1 sustains the activity of promoters and enhancers exclusively in MM but not in MGUS. A distinctive NRF1-dependent transcriptional signature of 103 genes was identified, correlating with aggressive disease and bad prognosis (CoMMpass dataset). This signature defines a group of 195 patients with a significantly poorer prognosis (20 months overall survival gap). The gene signature is enriched for survival pathways and ubiquitination. Our experiments show that NRF1 drives the proteasome homeostatic mechanism by enhancing phosphorylation and ubiquitination. NRF1 levels increase during therapy with proteasome inhibitors in our models. We identified a strong MM-specific enhancer element producing eRNA, looping towards the NRF1 gene. Interference with this eRNA downregulated NRF1 expression. Lowering eRNA in the presence of bortezomib increased cell proliferation loss, suggesting potential clinical applications for eRNA interference as an adjuvant to proteasome inhibitors.Collectively, our research supports that MM cells exhibit an addiction to NRF1, providing a survival advantage and therapy escape mechanisms. NRF1 binding reflects higher proteotoxic stress in malignant plasma cells and is crucial for their adaptability. Interfering with NRF1 and its regulatory elements significantly impairs MM therapy escape potential, highlighting its therapeutic benefit in MM treatment strategies.

overall_design: Gene expression profiling of CD138+ cells from patients with Mulitple Myeloma and MGUS

first: Clelia

last: Cortile

first: Maria Chiara

last: Cappelletto

first: Tiziana

last: Bruno

first: Stefano

last: Di Giovenale

first: Bruno

last: Amadio

first: Francesca

last: De Nicola

first: Italia

last: Falcone

last: Giuliani

first: Belinda

last: Palermo

first: Valeria

last: Catena

first: Ludovica

last: Ciuffreda

first: Fulvia

last: Cerruti

first: Paolo

last: Cascio

first: Roberta

last: Merola

first: Serena

last: Masi

first: Valentina

last: De Pascale

first: Ombretta

last: Annibali

first: Silvia

last: Ferraro

first: Svitlana

last: Gumenyuk

first: Francesco

last: Pisani

last: Marchesi

first: Andrea

last: Mengarelli

first: Giacomo

last: Corleone


title: Young KRAB-zinc finger gene clusters are highly dynamic incubators of ERV-driven genetic heterogeneity in mice

first: Melania

last: Bruno

state: Maryland

address: 6 Center Drive

institute: National Institutes of Health

summary: KRAB-zinc finger proteins (KZFPs) comprise the largest family of mammalian transcription factors, rapidly evolving within and between species. Most KZFPs repress endogenous retroviruses (ERVs) and other retrotransposons, with KZFP gene numbers correlating with the ERV load across species, suggesting coevolution. How new KZFPs emerge in response to ERV invasions is currently unknown. Using a combination of long-read sequencing technologies and genome assembly, we present a first detailed comparative analysis of young KZFP gene clusters in the mouse lineage, which has undergone recent KZFP gene expansion and ERV infiltration. Detailed annotation of KZFP genes in a cluster on Mus musculus Chromosome 4 revealed parallel expansion and diversification of this locus in different mouse strains (C57BL/6J, 129S1/SvImJ and CAST/EiJ) and species (Mus spretus and Mus pahari). Our data supports a model by which new ERV integrations within young KZFP gene clusters likely promoted recombination events leading to the emergence of new KZFPs that repress them. At the same time, ERVs also increased their numbers by duplication instead of retrotransposition alone, unraveling a new mechanism for ERV enrichment at these loci.

overall_design: ChIP-seq experiments for H3K3me3 and H3K9me3 in pure C57BL/6J mESCs and ChIP-seq experiments for individual mouse KRAB-zinc finger proteins overexpressed in F9 embryo carcinoma cells.

first: Sharaf

last: Farhana

first: Apratim

last: Mitra

first: Kevin

last: Costello

first: Dawn

last: Watkins-Chow

first: Glennis

last: Logsdon

first: Craig

last: Gambogi

first: Beth

middle: L

last: Dumont

first: Ben

last: Black

first: Thomas

last: Keane

first: Anne

last: Ferguson-Smith

first: Ryan

last: Dale

first: Todd

last: Macfarlan


title: Evaluating the potential and limitations of nanopore adaptive sampling for targeted transcriptome sequencing

city: Philadelphia

first: Lan

last: Lin

address: CTRB 9054 3501 Civic Center Blvd

department: Center for Computational and Genomic Medicine, Department of Pathology and Laboratory Medicine

institute: The Children’s Hospital of Philadelphia

summary: Long-read RNA sequencing is a powerful technology for transcriptomics, but low throughput and high cost pose challenges. Adaptive sampling, a feature of Oxford Nanopore Technologies, offers real-time enrichment by selectively ejecting non-target molecules. We evaluate adaptive sampling for human transcriptome analysis.

overall_design: Long-read sequencing on the Oxford nanopore platform was used to profile full-length transcript isoforms of preselected genes in poly(A)-selected RNA from SH-SY5Y human neuroblastoma cells, BT549 human breast cancer cells, and T47D human breast cancer cells.

first: Nicole

last: DeBruyne


title: Nuclear respiratory factor 1(NRF1) sustains the development, progression and resistance of Multiple Myeloma [RNA_seq_cell_lines_siNRF1]

first: Maurizio

last: Fanciulli

overall_design: Gene expression profiling of two multiple myeloma cell lines called KMS27 and KMS18 at control and NRF1 interfered condition.

first: Clelia

last: Cortile

first: Maria Chiara

last: Cappelletto

first: Tiziana

first: Stefano

last: Di Giovenale

first: Bruno

last: Amadio

first: Francesca

last: De Nicola

first: Italia

last: Falcone

last: Giuliani

first: Belinda

last: Palermo

first: Valeria

last: Catena

first: Ludovica

last: Ciuffreda

first: Fulvia

last: Cerruti

first: Paolo

last: Cascio

first: Roberta

last: Merola

first: Serena

last: Masi

first: Valentina

last: De Pascale

first: Ombretta

last: Annibali

first: Silvia

last: Ferraro

first: Svitlana

last: Gumenyuk

first: Francesco

last: Pisani

last: Marchesi

first: Andrea

last: Mengarelli


title: Nuclear respiratory factor 1(NRF1) sustains the development, progression and resistance of Multiple Myeloma [CHIP_seq_NRF1_in_patients]

first: Maurizio

last: Fanciulli

overall_design: Chromatin immunoprecipitation DNA-sequencing (ChIP-seq) for NRF1 in primary plasma cell lines derived in-house from patients with MM and MGUS.

first: Clelia

last: Cortile

first: Maria Chiara

last: Cappelletto

first: Tiziana

last: Bruno

first: Stefano

last: Di Giovenale

last: Amadio

last: De Nicola

first: Giacomo

last: Corleone


title: Transcriptome analysis of olive mesocarps during olive fruit maturation

city: Athens

first: Stamatis

last: Rigas

state: Attiki

address: Iera Odos 75

department: Biotechnology

country: Greece

institute: Agricultural University of Athens

summary: Olive oil is a primary source of human health-beneficial compounds, establishing olive trees as one of the most vital and valued crop species worldwide. In this study, we performed a transcriptomic analysis across four distinct developmental stages of olive drupes from the emblematic cultivar "Koroneiki".

overall_design: The fruit samples were collected during the 2019 growing season. The olive trees (Olea europea L., cultivar “Koroneiki”) were grown in a field, located on a hilly area near the location of ancient Olympia in Western Greece (40°48′43’’ N, 23°59′25’’ E, at an altitude of 330 m). Irrigation, fertilization, pest and canopy management were applied according to standard local agronomical practices. Samples were collected at four time points during fruit maturation, specifically at 17, 21, 26 and 30 Weeks After Flowering (WAF). At each time point, fruits of the same developmental stage (similar color, size, and shape) were selected and sampled.

first: Dikran

last: Tsitsekian

first: Gerasimos

last: Daras


title: Nuclear respiratory factor 1(NRF1) sustains the development, progression and resistance of Multiple Myeloma [CHIP-seq_NRF1_in_cell_lines]

overall_design: Chromatin immunoprecipitation DNA-sequencing (ChIP-seq) for NRF1 in KMS27, KMS18, two in-house primary plasma cell lines called MM217 and MM196.

first: Bruno

first: Francesca

first: Italia

last: Falcone

last: Giuliani

first: Belinda

last: Palermo

first: Valeria

last: Catena

first: Ludovica

last: Ciuffreda

first: Fulvia

last: Cerruti

first: Paolo

last: Cascio

first: Roberta

last: Merola

last: Masi

last: De Pascale

last: Annibali


title: Synapse-centered novel omics targets in Alzheimer’s disease

first: Enrique

last: Ramos

overall_design: We used postmortem brains from AD (n=27) and controls (n=14). Synaptosomes were isolated from AD and control brains. Further, total RNA were isolated from the synaptosome and subjected to miRNA and mRNA HiSeq analysis.

first: Ramos

last: Enrique

first: Hidalgo

last: Axel

first: Gadad

last: Shrikanth

first: Kumar

last: Subodh

first: Sharma

last: Bhupender

first: Rodarte

last: Daniela

first: Devara

last: Davin


title: Nuclear respiratory factor 1(NRF1) sustains the development, progression and resistance of Multiple Myeloma

first: Maurizio

last: Fanciulli

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

overall_design: Refer to individual Series


title: Transthyrectin, a novel prognostic marker of POCD revealed by time-series RNA sequencing analysis

city: Guangzhou

first: Yi

last: Zou

address: West Huangpu Avenue

institute: Jinan University

summary: Postoperative cognitive dysfunction (POCD) is defined as a declined cognition, measured by neuropsychological tests, that persists for months or even longer after surgery. Heterogeneities in the diagnosis of POCD usually involve differences in the test batteries, the cutoffs, and the timing of assessments. Although peripheral and CSF markers of neuroinflammation have been shown to correlate with increased risk of POCD, most of them are non-specific and cannot be used for POCD diagnosis. These factors hampered the understanding of the pathogenesis of POCD as well as the development of effective preventions/treatments. In this study, we found Ttr in a panel of potential POCD biomarkers identified using time-series analysis of the transcriptomes and proteomes of the hippocampi of POCD mice that diagnosed on individual basis with composite Z-scores of test batteries consisting of Y maze and open field test. Compared with their counterparts without POCD, the levels of Ttr were significantly lower in the peripheral circulation as well as in the microglia and interstitials space in the hippocampi of the mice developed POCD at all indicated time points after surgery. Significantly lower levels of peripheral TTR were also found in human patients that displayed impaired cognition after abdominal surgeries, compared with those who did not. Endogenous expression of Ttr was verified in microglia cells both in vitro and in vivo. Results of in vitro assay indicated a potential role of Ttr in ameliorating LPS-induced microglial priming and protecting the differentiation of oligodendrocyte progenitor cells (OPCs) in proinflammatory microenvironment, which was one of the determinant factors in regulating the pathological progression of POCD.

overall_design: C57BL/6J mice aged 16 months underwent Y maze and open field experiment 24 hours before surgery, then underwent abdominal and small intestinal restoration, and then underwent Y maze and open field experiment with environmental parameters at 24 hours(24hps), 3 days(3dps), 7 days(7dps), and 1 month(1mps) after surgery, respectively. After behavioral experiment, the mice were anesthetized, and hippocampal tissues were collected after perfusion. Control mice did not undergo surgery. Progressive transcriptome sequencing of hippocampal tissue was performed in mice diagnosed with POCD and in control mice.

first: Xiaosheng

last: Liang

first: Olivia

first: Hongyu

last: Yao


title: Nuclear respiratory factor 1(NRF1) sustains the development, progression and resistance of Multiple Myeloma [CUTandRUN-seq_histone_modifications]

overall_design: Cleavage Under Target & Tagmentation sequencing  (CUT&TAG-seq) for histone modification H3k27Ac,H3k27me3,H3k4me3,H3k4mono,H3k9me3 in two in-house primary plasma cell lines, MM217 and MM196.

first: Clelia

last: Cortile

first: Maria Chiara

last: Cappelletto

first: Tiziana

last: Bruno

first: Stefano

last: Di Giovenale

first: Bruno

last: Amadio

first: Francesca

last: De Nicola

first: Italia

last: Falcone

last: Giuliani

first: Belinda

last: Palermo

first: Valeria

last: Catena

first: Ludovica

last: Ciuffreda

last: Cerruti

last: Cascio

first: Serena

first: Valentina

first: Ombretta

first: Silvia

last: Ferraro

first: Svitlana

last: Gumenyuk

first: Francesco

last: Pisani

last: Marchesi

first: Andrea

last: Mengarelli

first: Giacomo

last: Corleone


title: Transcriptome changes of fission yeast cells exposed to fumonisin B1 or co-cultured with Fusarium verticillioides

city: Debrecen

first: Laszlo Attila

last: Papp

state: Hajdú-Bihar Vármegye

address: Egyetem tér 1.

department: Department of Genetics and Applied Microbiology

country: Hungary

institute: University of Debrecen

summary: Fusarium verticillioides poses a high food safety risk worldwide due to its mycotoxin production. Successful control of Fusaria may rely on promising biocontrol agents, including yeasts. Although the fission yeast Schizosaccharomyces pombe tolerated Fusarium mycotoxins well, including zearalenone, T2, deoxynivalenol, and fumonisins (FUMs), it did not significantly inhibit the growth of F. verticillioides. Meanwhile fumonisin B1 (FB1) supplementation did not decrease S. pombe cell density in submerged liquid cultures, the colony-forming capability of the yeast was reduced. RNA sequencing showed that S. pombe genes involved in cell adhesion and flocculation were down-regulated after FB1 exposure. In addition, the expression of several hydrolase genes was also altered. In co-cultures with F. verticillioides, genes encoding oxidoreductases and hydrolases and those linked to purine nucleotide metabolisms were down-regulated, while the expression of genes involved in membrane and transport processes was increased.  The expression of several F. verticillioides genes also changed after co-cultivation. Oxidoreductase, transmembrane transport, and purine metabolism genes were up-regulated under co-culturing, meanwhile hydrolase genes, together with carbon metabolism and polysaccharide catabolism genes were down-regulated. Co-cultivation also decreased fumonisin production via the down-regulation of genes FUM19, FUM21, and FvATFA encoding the fumonisin transporter, a local Zn(II)2Cys6-type transcriptional regulator and an important global regulator bZIP-type transcription factor, respectively. Although further experiments should clarify the mechanism of the fission yeast-elicited inhibition of fumonisin production, these results may pave the way for the development and implementation of novel, innovative approaches to control mycotoxin production by F. verticillioides in the feed and food chain.

sample_organism:
Schizosaccharomyces pombe
Fusarium verticillioides

overall_design:
To investigate the gene expression changes in Schizosaccharomyces pombe and Fusarium verticilloides during co-cultivation using RNA sequencing.
Samples:
Control S. pombe (14 - S. pombe control)
Control F. verticilloides (F3 - F. verticilloides control)
Co-cultured S. pombe with F. verticilloides (6 - S. pombe co-cultivated with F. verticilloides)
Co-cultured F. verticilloides with S. pombe (Fv3 - F. verticilloides co-cultivated with S. pombe) Each samples have 2 technical replicates.
Control Groups: S. pombe and F. verticilloides grown separately.
Co-cultivation Groups: S. pombe and F. verticilloides grown together to assess the impact of co-cultivation on gene expression.
To investigate the gene expression changes in Schizosaccharomyces pombe in  exposure to 0.5 ppm fumonisin B1
Samples:
Control S. pombe (K1 - S. pombe control)
Control F. verticilloides (M1 - S. pombe treated with 0.5 ppm fumonisin B1)
Each samples have 3 technical replicates.
Control Group: S. pombe grown in MXGB media.
Treated Group: S. pombe grown in MXGB media supplemented with 0.5 ppm fumonisin B1.

first: Laszló

first: Lajos

last: Ács-Szabó

first: Gyula

last: Batta

first: Ida

last: Miklós


title: Nuclear respiratory factor 1(NRF1) sustains the development, progression and resistance of Multiple Myeloma [ATAC-seq_cell_lines_NRF1]

first: Maurizio

last: Fanciulli

overall_design: To identify accessible chromatin regions in Multiple Myeloma, we performed Assay for Transposase-Accessible Chromatin using sequencing (ATAC-seq) on commercial B cell lines (KMS27, RPMI8226, U266) and in-house cultured CD138+ plasma cells (MM196).

first: Clelia

last: Cortile

first: Maria Chiara

last: Cappelletto

first: Tiziana

last: Bruno

first: Stefano

last: Di Giovenale

first: Bruno

last: Amadio

first: Francesca

last: De Nicola

first: Italia

last: Falcone

first: Fulvia

first: Paolo

first: Roberta

last: Merola

last: Masi

last: De Pascale

last: Annibali


title: Nuclear respiratory factor 1(NRF1) sustains the development, progression and resistance of Multiple Myeloma [ATAC-seq_patients_NRF1]

overall_design: To detect accessible chromatin regions at the MM and MGUS stages, we performed Assay for Transposase-Accessible Chromatin using sequencing (ATAC-seq) on CD138-positive plasma cells isolated from the bone marrow of patients at these stages.

last: Giuliani

first: Belinda

last: Palermo

first: Valeria

last: Catena

first: Ludovica

last: Ciuffreda

last: Cerruti

last: Cascio

first: Serena

first: Valentina

first: Ombretta

first: Silvia

last: Ferraro

first: Svitlana

last: Gumenyuk

first: Francesco

last: Pisani

last: Marchesi

first: Andrea

last: Mengarelli

first: Giacomo

last: Corleone


title: Persistent open chromatin state in early-life stress-activated cells of the VTA

city: Princeton

first: Catherine

middle: Jensen

last: Peña

state: NJ

address: Princeton Neuroscience Institute, Washington Road, Lot 20

institute: Princeton Neuroscience Institute

summary:
Early-life stress sensitizes individuals to subsequent stressors to increase lifetime risk for psychiatric disorders. Within the ventral tegmental area (VTA), a mesolimbic brain region implicated in stress response and mental health, early-life stress causes long-lasting changes in gene expression and chromatin modifications that in turn cause latent physiological and behavioral sensitivity to stress. These molecular consequences of early-life stress are indicative of epigenetic priming, a form of molecular memory in which developmental or environmental cues open chromatin at enhancers to facilitate transcriptional response to stimuli. However, the long term impact of early-life stress on chromatin architecture in the VTA was not yet known. Using a combination of activity-dependent cellular tagging and ATAC-sequencing, we find that early-life stress opens chromatin specifically in stress-activated cells of the VTA, that this remodeling persists into adulthood, and that opening chromatin at cis-regulatory elements
including enhancers augments transcriptional response to adult stress. Together, this data supports enhancer priming within ELS-responsive cells in the VTA as a biological mechanism for lifelong stress sensitivity.

overall_design: bulk ATAC-seq (assay for transposase accessible chromatin) from the ventral tegmental area (VTA) of adult (>postnatal day 60) Mus musculus.

first: Rebekah

last: Rashford

first: Michael

last: DeBerardine

first: Shu

last: Dan

first: Shannon

last: Bennett

middle: J


title: Next Generation Sequencing Analysis of Transcriptome Profile in CRISPR/Cas9 U90926KO IEC4.1 Cells Treated with IFN-gamma protein (IFNγ)

first: Aiyu

last: Gong

address: 1735 W. Harrison St

department: MPI

institute: Rush University

summary: Interferon-gamma protein (IFNγ) plays a key role in intestinal epithelial cell-autonomous defense against microbial infection. The underlying mechansims of host immune regulation remains obscure and increasing evidence has shown long non coding RNAs (lncRNAs) can regulating gene expression at both the transcriptional and posttranscitpional levels. In the current study, we analyzed the transcriptome of murine intestinal epithelial cells (IEC4.1 cells) or stable CRISPR/cas9 U90926KO IEC4.1 cells following treatment with IFNγ to identify potential immune gene tragets of this lncRNA. Total RNA was collected for the genome-wide analysis, for sequencing using  DNBSEQ platform.

overall_design: Cells were with or without IFNγ treatment (2ng/ml, 4 hours).  Total RNA was collected. Comparative gene expression profiling analysis of RNA-seq data for intestinal epithelial cells or CRISPR/Cas9 U90926KO cells with or without IFNγ treatment.

first: Xianming

last: Chen


title: Ago2-Mediated Recruitment of HP1a on Transposable Elements in Drosophila Brain

status: Public on Sep 08 2025

city: Moscow

first: Yuri

last: Shevelyov

address: Kurchatov sq., 2

country: Russia

institute: National Research Centre “Kurchatov Institute”

summary: In Drosophila gonads, transposable elements (TEs) are repressed by Piwi-interacting RNA (piRNA) pathway operating both co-transcriptionally and post-transcriptionally. In the non-gonadal tissues, TEs are mainly repressed by short interfering RNA (siRNA) pathway with Argonaute2 (Ago2) as an effector protein. It is generally assumed that this pathway acts at the post-transcriptional level. However, recent data point to its involvement in the co-transcriptional silencing. Here, using DamID, we found drastic decrease of HP1a on TEs (especially on the LTR-containing retrotransposons) and other heterochromatin regions in Ago2-mutant Drosophila brain. HP1a reduction is accompanied by the increased chromatin accessibility of TEs, indicating their derepression. Consistent with these findings, several LTR-containing retrotransposons were up-regulated in larval brain upon Ago2 mutation. Moreover, upon knock-down of lamin Dm0 in neurons, HP1a was increased predominantly on the same set of TEs that have the reduced HP1a binding upon Ago2 mutation. We hypothesize that, since Ago2 was revealed in the common complex with lamin Dm0, the depletion of the latter may release Ago2 in the nucleoplasm, thus enhancing the recruitment of HP1a on TEs. Our findings support the model that TEs in Drosophila brain are partially silenced through Ago2-mediated recruitment of HP1a.

overall_design: DamID-seq


title: Autoimmunity-associated DIORA1 binds the MRCK family of serine/threonine kinases and controls cell motility

city: Solna

first: Tilen

last: Trselic

address: Visionsgatan 18

institute: Karolinska Institutet

summary: Genetic association links DIORA1 to numerous autoimmune rheumatic diseases, including systemic lupus erythematosus, Sjögren's disease, rheumatoid arthritis, polymyositis and systemic sclerosis. However, its cellular function has remained unknown. Here, we identify the MRCK family of serine/threonine kinases - key regulators of actomyosin contractility and cell motility - as direct interactors of DIORA1. Through interaction mapping, we show that DIORA1 binds three distinct modules of MRCK kinases, including the conserved kinase inhibitory motif (KIM), C1-PH and CNH domains. DIORA1 knockdown in human cells altered cellular phosphorylation patterns and reduced phosphorylation of known MRCK targets. RNA-sequencing and proteomic analyses revealed upregulation of epithelial-mesenchymal transition genes and proteins, and functional analyses confirmed increased cell invasion, following knockdown of DIORA1. Together, these findings identify the autoimmunity-associated DIORA1 protein as a previously uncharacterized interactor of MRCK kinases and a regulator of cell motility.

overall_design: RNA-seq profiling of SK-N-SH and SK-N-AS neuroblastoma cell lines following knockdown of the gene FAM167A (DIORA1). Knockdown was achieved using either CRISPR interference (CRISPRi) with SpCas9-KRAB in both cell lines, or pooled siRNA targeting FAM167A in SK-N-SH cell line.

last: Tršelič

first: Nathalie

last: Pelo

first: Gregoire

last: Martin de Fremont

first: Vaishnavi

last: Iyer

first: Elina

last: Richardsdotter Andersson

first: Vijole

last: Ottosson

first: David

last: Frei

first: Elisa

last: Baas

first: William

last: Nyberg

first: Guðný Ella

last: Thorlacius

first: Lara

last: Mentlein

first: Sanjaykumar

middle: V

last: Boddul

first: Ioana

last: Sandu

first: Diego

last: Velasquez Pulgarin

first: Ákos

last: Végvári

first: Carmen

last: Gerlach

first: Fredrik

last: Wermeling

first: Maria

last: Sunnerhagen

first: Björn

last: Wallner

first: Alexander

last: Espinosa

first: Marie

last: Wahren-Herlenius


title: Clearance of intracranial debris by ultrasound reduces inflammation and improves outcomes in hemorrhagic stroke models

city: Stanford

first: Arjun

last: Rajan

state: California

address: 265 Campus Drive

institute: Stanford University

summary: Impaired clearance of the byproducts of neurologic injury exacerbates disease progression and severity. We have developed a noninvasive, low intensity transcranial focused ultrasound protocol that facilitates removal of pathogenic substances from the cerebrospinal fluid (CSF) and brain interstitium. This protocol clears blood products from the central nervous system in two mouse models of hemorrhagic brain injury. Cleared blood products accumulate in the cervical lymph nodes from both the CSF and interstitial compartments, indicating clearance through meningeal lymphatics. Treatment with this ultrasound protocol reduced neuroinflammation and neurocytotoxicity, improved behavioral outcomes, decreased morbidity and, importantly, increased survival. Clearance efficacy was independent of thermal effects, given the lack of significant heating noted by simulation and experimental verification. Instead, protocol application was associated with a shift of microglial polarization to a homeostatic state and an increase of astrocytic endfeet aquaporin-4 polarization. As these processes are thought to be downstream of mechanosensitive channels, we confirmed that blockade of mechanosensitive channels blocks clearance and that the protocol was effective when applied in anesthetized subjects. This indicates that ultrasound acts as a non-pharmacologic agonist of mechanosensitive channels to induce these homeostatic immune and glymphatic effects, in a way that does not depend on sensory stimulation or a specific neural activity pattern. Notably, the low intensity of this protocol is within FDA guidelines for safe ultrasound application, making it readily clinically translatable. Overall, our results demonstrate that this low-intensity transcranial focused ultrasound protocol induces cellular processes that clear hemorrhagic products from the brain via the meningeal lymphatic system, offering a novel therapeutic tool for the clearance of other neurotoxic byproducts in varied neurologic disorders.

overall_design: Spatial transcriptomics using STOmics stereo-seq of 4 samples, Control, Control+UCC, ICH, ICH+UCC.

first: Matine

middle: M

last: Azadian

first: Sepideh

last: Shabestari

first: Payton

last: Martinez

first: Nicholas

last: Macedo

first: Eric

last: Markarian

first: Yun

last: Xiang

first: Brenda

last: Yu

first: Paul

last: George

first: Ryann

last: Fame

first: Raag

middle: D

last: Airan


title: Chronic HIF1A  activity in rod photoreceptors causes type 3 neovascularization and retinal atrophy

city: Schlieren

first: Christian

last: Grimm

state: Zürich

address: Wagistrasse 14

department: Department of Ophthalmology

country: Switzerland

institute: Universität Zürich

summary: Morphological changes in the ageing eye impede oxygen delivery from the choroid to the outer retina causing tissue hypoxia, which activates a molecular response that adapts the transcriptomic fingerprint of the retina and retinal pigment epithelium (RPE). This response, orchestrated by hypoxia-inducible transcription factors (HIFs), leads to the production of pro-angiogenic factors and plays a critical role in the pathogenesis of age-related macular degeneration (AMD). To evaluate the specific contribution of HIF1 to this response we expressed a constitutively active form of HIF1A in rod photoreceptors of the adult mouse retina. This elicited a transcriptional response characterized by the upregulation of genes involved in cell death, inflammation and angiogenesis, all of which play an important role in AMD. The HIF1-mediated response in rods caused severe retinal degeneration, disruption of the RPE and retinal neovascularization. Pathological vessels originated from the deep vascular plexus and penetrated the RPE resembling type 3 macular neovascularization found in over 20% of neovascular AMD patients. Our study provides further evidence for the involvement of tissue hypoxia in the pathogenesis of AMD and highlights the potential of HIF1A as a potential therapeutic target.

overall_design: Bulk RNA-seq profiling of  661W cell upon Hif1a overexpression by transfection and C57BL/6J mouse retina upon subretinal injection of AAVs. Comparison with eGFP expressed cells and retinas.

first: Fredy

last: Geiger

first: Thomas

last: Heigl

first: Luca

last: Merolla

first: Marcus

last: Yong

first: Gabriele

last: Wögenstein

first: Larissa

middle: P

last: Govers

first: Ioanna

last: Tsioti

first: Antonia

last: Fottner

first: Marijana

last: Samardzija


title: Circular RNA profiling in gastric cancer and matched non-tumor tissues

first: Rongpeng

last: Chen

state: Guangdong Province

address: No. 250 Changgang East Road, Haizhu District

department: Department of Gastrointestinal Surgery

country: China

institute: The Second Affiliated Hospital of Guangzhou Medical University

summary: To explore the potential role of circular RNAs in gastric cancer, we employed microarray profiling as a discovery platform. Circular RNA expression was analyzed in three paired gastric cancer and adjacent non-tumor tissues using the Arraystar Human circRNA microarray V2 (Agilent one-color). Quantile normalization and statistical testing identified circRNAs differentially expressed between tumor and non-tumor tissues, providing candidate biomarkers for gastric cancer.

overall_design: Circular RNA expression in gastric cancer was measured using paired tumor and adjacent non-tumor tissues. Three independent paired tissue samples were analyzed on the Arraystar Human circRNA microarray V2 (Agilent one-color).


title: Ikaros-binding genomic sequences in mouse thymic iNKT cells and total thymocytes (ChIP-seq)

first: Eri

last: Ishikawa

address: 3-1 Yamadaoka

institute: Osaka University

summary: We have conducted ChIP-seq analysis to investigate Ikaros-regulating genes in mouse thymic iNKT cells. Total thyomcytes were also analyzed as a control. Results demonstrate that Ikaros-binding genomic sequences are different between total thymocytes and thymic iNKT cells.

overall_design: Thymic iNKT cells were purified from iNKT-iPS cell-derived mice by CD1d-tetramer using MACS magnetic separators. Total thymocytes from wild-type mice and purified thymic iNKT cells were applied to ChIP-seq analysis using anti-Ikaros antibody. ChIP-seq analysis was done by Active Motif.

first: Sho

last: Yamasaki