title: Protective efficacy and related mechanism of deinoxanthin in experimental animal and cell models of periodontitis

status: Public on Feb 13 2026

city: Jeonbuk

first: JungChae

last: Lee

address: 567, Baekje-daero, Deokjin-gu, Jeonju-si, Jeollabuk-do, Republic of Korea

country: South Korea

institute: Jeonbuk National University

summary: As periodontitis is a chronic inflammatory disease resulting in periodontal tissue destruction and tooth loss, studies have tried to development the biomaterials that effectively prevent inflammatory response and oxidative stress without side effects. In this work, we explored whether Deinococcus radiodurans-derived deinoxanthin (DEIX) protects against alveolar bone loss and connective tissue degradation in an experimental rat model of periodontitis investigated the related mechanisms. Oral supplementation with DEIX (25 mg/kg body weight, once per day for 14 consecutive days) protected rats against ligature-mediated loss of alveolar bone and connective tissues. That protection involved the DEIX-induced restoration of the ligature-stimulated disorders, including overproduction of inflammatory mediators, accumulation of reactive oxygen species, and imbalance between osteoclast and osteoblast activity in the inflamed periodontium. In vitro experiments using human periodontal ligament cells (hPDLCs) and THP-1 cells supported the mechanisms by which the direct addition of DEIX (20 μM) recovers lipopolysaccharide (LPS, 2 μg/mL)-stimulated inflammatory responses in the cells. RNA-sequence profiling from the hPDLCs further supported the potency and the related mechanisms of DEIX to protect cells from LPS-mediated inflammatory damages. Collectively, this study introduces the protective role of DEIX in inflammatory periodontal tissue destruction and supports its clinical usefulness for patients who suffering from chronic periodontitis.

overall_design: Total RNAs were isolated from human-derived periodontal ligament cells (hPDLCs) for RNA-sequence profiling. In this study, the hPDLCs were exposed to 2 μg/mL lipopolysaccharide (LPS) for seven days followed by the additional-14 days incubation in combination with 20 μM DEIX or not before the RNA extraction. There are four groups: 1) non-treated control hPDLCs (Control-C1-I, C1-II, C1-III), 2) LPS treatment alone (LPS-C2-I, C2-II, C2-III ), 3) LPS and DEIX treatment (LPS+DEIX-C3-I, C3-II, C3-III), and 4) DEIX treatment alone (Only DEIX-C4-I, C4-II, C4-III).

first: Jung-Chae


title: CFP1-mediated H3K4me3 broad domains control early B cell lineage fate determination [VDJ-Seq]

status: Public on Feb 08 2026

city: Shenzhen

first: Wanyu

last: Bai

address: 628 Zhenyuan Road

country: China

institute: The Seventh Affiliated Hospital of Sun Yat-Sen University

summary: Histone H3K4me3 broad domain (BD) is a unique epigenetic feature to mark cell identity-associated genes, but its physiological role in lineage differentiation remains unclear. Here we show that CFP1, an integral component of the Setd1A/B methyltransferase complex, is critically required for functional H3K4me3-BD installation and B cell fate determination. Cfp1 deletion impairs H3K4me3-BDs on a subset of B-lineage genes and redistributes H3K4me3 from active genes to bivalent promoters. Transcription of subsets of H3K4me3-BD-bound gene is diminished in part due to reduced RNA Pol II at the promoter and gene body. Specifically, CFP1 ablation abolishes H3K4me3-BD at the recombination center and distal PAIR elements in the immunoglobulin heavy chain (IgH) gene, severely compromises its locus contraction for efficient V-to-DJ recombination and consequently arrests cells at the pro-B stage. Moreover, Cfp1-deficient pro-B cells upregulate a panel of progenitor and myeloid-specific genes with elevated H3K4me3 marks and can trans-differentiate into various myeloid cell types. Therefore, our study reveals pivotal roles for CFP1-mediated H3K4me3-BDs in the transcriptional regulation of cell lineage fate specification and commitment.

overall_design: We performed CUT&Tag, ChIP-seq, RNA-seq, V(D)J-HTGTS and 4C-HTGTS in murine pro-B cells to study roles of CFP1-regulated epigenetic program in early B cell development.

first: Yalin

last: Yang

first: Yanan

last: Zhao

first: Shuoxu

last: Gong

first: Yimiao

last: Lu

first: Zhonghui

last: Xue

first: Lie

last: Wang

first: Fei-Long

last: Meng

first: Chun

last: Chen

first: Junchao

last: Dong


title: LIVER EXERCISE FACTOR REVERSES AGING- AND ALZHEIMER’S-RELATED MEMORY LOSS BY TARGETING BRAIN VASCULATURE

status: Public on Feb 09 2026

city: San Francisco

first: Yasuhiro

last: Fuseya

state: CA

address: 513 Parnassus Ave Bldg S1364, Medical Science

department: Anatomy

country: USA

institute: University of California, San Franc

type: Expression profiling by high throughput sequencing

summary: Blood factors transfer the benefits of exercise to the aged brain, independent of physical activity. Here we show that liver-derived exercise factor glycosylphosphatidylinositol (GPI)-specific phospholipase D1 (GPLD1), a GPI-degrading enzyme, reverses aging- and Alzheimer’s-related memory loss by targeting brain vasculature. GPLD1 has potential to cleave over 100 putative GPI-anchored proteins, necessitating identification of downstream targets that mediate cognitive rejuvenation for translational application. We identified GPI-anchored tissue-nonspecific alkaline phosphatase (TNAP) on brain vasculature as a GPLD1 substrate. Mimicking the age-related increase in cerebrovascular TNAP impaired blood-brain transport and cognition in young mice and mitigated Gpld1-induced cognitive benefits in aged mice. Inhibiting TNAP recapitulated benefits of GPLD1 in old age, restoring youthful hippocampal transcriptional signatures and rescuing cognition. In an Alzheimer’s disease model, increasing GPLD1, or inhibiting TNAP, ameliorated Ab pathology and improved cognitive deficits. We thus identify brain vasculature as a mediator of the cognitive benefits of a liver-to-brain exercise axis.

overall_design: Hippocampal brain endothelial cells (BECs) isolated from young and aged control mice, aged mice with liver expression of GPLD1 and aged mice treated with a TNAP inhibitor (TNAPi) using fluorescence activated cell sorting (FACS). Pool of 8 mice/group.

first: Fuseya

last: Yasuhiro

first: Bieri

last: Gregor

first: Pratt

last: Karishma


title: A lung specific escape of intravascular metastatic breast cancer cells from cytotoxic T cell killing

city: Rehovot

first: Marina

last: Kizner

address: 234 Herzel st.

country: Israel

institute: Weizmann Institute of Science

summary: The lungs are a major organ of cancer metastasis. Despite advances in the usage of tumor-specific cytotoxic T cells (CTLs) with potent killing activity (i.e., tumor infiltrating T cells, TILs) for killing of primary tumors, how these T cells encounter and kill metastatic lesions at remote organs is still poorly understood. In the present study we compared the ability of potent neoantigen specific CTLs to kill two types of cancer cells that share the same neoantigen and generate distinct metastatic lesions in the lungs of immunocompetent recipient mice. We have used ovalbumin (OVA) as a neoantigen model and found that the OVA-specific OT-I transgenic CD8 CTLs, when intravenously introduced, readily eliminated primary tumors of OVA-expressing breast cancer E0771 cells. Nevertheless, similar OT-I CTLs failed to clear OVA-expressing breast cancer E0771 cells that colonized the lungs. In contrast, similar intravenously introduced OT-I CTLs efficiently eliminated lung metastatic OVA-expressing B16 melanoma cells, ruling out that the intravenous CTLs were exhausted upon entering the lungs. Three-dimensional (3D) imaging of whole lungs revealed that in both experimental and spontaneous metastasis models, the OVA E0771 cells survived inside lung blood vessels but did not recruit circulating OT-I CTLs to their vicinity. Furthermore, canonical vascular adhesion molecules recognized by the CTLs like ICAM-1 and VCAM-1 were not upregulated nearby the lung-residing intravascular E0771 cells as a potential means to recruit lung circulating CTLs to the vicinity of the intravascular tumor cells. Strikingly, the lung residing OVA-expressing E0771 cells lost expression of their OT-I specific OVA-derived SIINFEKL-H-2Kb pMHC complexes while retaining MHC-I expression. This loss was accompanied by a lung-specific transcriptional reduction of key regulators of MHC-I presentation. A temporal loading of OVA-derived SIINFEKL-H-2Kb pMHC complexes on E0771 cells did not result, however, in cancer cell killing inside the lungs. Nevertheless, direct and stable SIINFEKL peptide presentation on these cells overcame their lung specific escape from OT-I mediated killing. Our study is a first indication that subsets of cancer cells that reside in the lungs rapidly downregulate the expression of neoantigen derived peptide MHC-I complexes and thereby evade killing by intravenously introduced tumor antigen-specific CTLs.

overall_design: 106 OVA-RFP E0771 cells were introduced i.v., and 3 days later fluorescent cells were sorted from whole lungs using FACS Aria III Cell Sorter. Cells were collected in the presence of Actinomycin D (Sigma-Aldrich, cat. A1410) in order to minimize ex vivo RNA transcription. RNA was purified from the sorted cells using the QIAGEN Rneasy kit. A second experimental group consisted of 103 OVA- RFP E0771 cells implanted in mammary fat pads to generate primary tumors. Cells from primary tumors were similarly isolated and sorted on day 14 post implantation.

first: Nehora

last: Levi

first: Carmel

last: Sochen

first: Julia

last: Ryvkin

first: Ofer

last: Regev

first: Alexander

last: Zarbock

first: Lea

last: Eisenbach

first: Moshe

last: Biton

first: Ronen

last: Alon


title: CFP1-mediated H3K4me3 broad domains control early B cell lineage fate determination

first: Wanyu

last: Bai

type: Genome binding/occupancy profiling by high throughput sequencing

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

overall_design: Refer to individual Series


title: The Arp5-Ies6 module is essential for INO80-mediated nucleosome organization

status: Public on Feb 10 2026

city: Paris

first: Ashish

middle: Kumar

last: Singh

state: Ile-de-France

address: 25-28 Rue du Dr Roux

department: Development and Stem Cell Biology

country: France

institute: Institute Pasteur

summary: ATP-dependent nucleosome remodelers of the INO80 family regulate chromatin by sliding, spacing and positioning nucleosomes. The INO80 remodeler is organized into structural modules that regulate its remodeling activity. Here, we investigate the role of the essential Arp5-Ies6 module towards nucleosome positioning and spacing in S. cerevisiae. We show that the Arp5-Ies6 module is critical for establishing genome-wide nucleosome organization. Deletion of IES6 reduces nucleosome spacing by 3 bp and disrupts regular nucleosome arrays across most genes. Surprisingly, deletion of IES6 is synthetic lethal with the deletion of ISW2, a remodeler from the ISWI family, indicating functional redundancy in nucleosome organization. Notably, INO80 binding directly predicts the role of Arp5-Ies6 in nucleosome organization, whereas changes in gene expression do not correlate with altered nucleosome spacing or array regularity. Together, our results highlight the essential role of the Arp5-Ies6 module in INO80-mediated chromatin organization.

middle: K

first: Felix

last: Mueller-Planitz


title: CFP1-mediated H3K4me3 broad domains control early B cell lineage fate determination [Cut&Tag]

first: Yalin

last: Yang

first: Yanan

last: Zhao

first: Shuoxu

last: Gong

first: Yimiao

last: Lu

first: Zhonghui

last: Xue

first: Lie

last: Wang

first: Fei-Long

last: Meng

first: Chun

last: Chen

first: Junchao

last: Dong


title: RNA-seq of sipinal cord of WT, AR-24Q, AR-97Q, testosterone-treated AR-97Q mice, Scramble-ASO-treated AR-97Q mice, and Rest4-ASO #3-treated AR-97Q mice at P7

city: Nagoya

first: Tomoki

last: Hirunagi

state: Aichi

address: 65 Tsurumai-cho, Showa-ku

department: Neurology

country: Japan

institute: Nagoya University GraduateSchool of Medicine

summary: Testosterone (20 mg) was subcutaneously adminstered to AR-97Q mice at postnatal day 1 (P1). Scramble-ASO and Rest4-ASO #3 were intracerebroventriculary administred to AR-97Q mice at P1.Gene expression profiles were analysed in the spinal cord of WT, AR-24Q, AR-97Q, testosterone-treated AR-97Q mice, Scramble-ASO-treated AR-97Q mice, and Rest4-ASO #3-treated AR-97Q mice at P7.

overall_design: RNA-seq analysis was performed in the mouse spinal cord at P7 (WT, AR-24Q, AR-97Q, testosterone-treated AR-97Q mice , Scramble-ASO-treated AR-97Q mice, and Rest4-ASO #3-treated AR-97Q mice).

first: Kentaro

last: Sahashi

first: Masahisa

last: Katsuno


title: Identification of specific binding sites of ADR-1 in vivo

city: Bloomington

first: Boyoon

address: 1001 E 3rd St

institute: Indiana University

summary: We used eCLIP to identify in vivo binding sites of ADR-1, a member of the adenosine deaminase acting on RNA (ADAR) family of dsRBPs in Caenorhabditis elegans, using 3xFLAG ADR-1 animals.

overall_design: CLIP-seq was performed to identify in vivo binding sites of ADR-1 using 3xFLAG ADR-1 animals (HAH59).

first: Douglas

middle: B

last: Rusch

first: Heather

middle: A

last: Hundley


title: CFP1-mediated H3K4me3 broad domains control early B cell lineage fate determination [RNA-Seq]

first: Wanyu

last: Bai


title: CFP1-mediated H3K4me3 broad domains control early B cell lineage fate determination [ChIP-Seq]


title: Characterisation of thyroid 8505 cells treated with CUET (RNA-Seq)

status: Public on Feb 06 2026

city: Detroit

first: Moray

last: Campbell

state: MI

address: 4100 John R

institute: Barbara Ann Karmanos Cancer Institute, Detroit , Michigan, US

summary: In this study, we examined the impact of copper diethyldithiocarbamate (Cu(DDC)2), a metabolite of the FDA-approved drug disulfiram, on thyroid cancer cells. Mechanistically, Cu(DDC)2  targets valosin containing protein (VCP) – a key regulator of proteostasis – as well as inducing potent transcriptional responses.

overall_design: Thyroid cancer 8505C cells were treated with Cu(DDC)2 (250 nM, 24 hours) versus vehicle (DMSO). RNA-Seq libraries were prepared at the Next Generation Sequencing Facility (Genomics Birmingham Genomics Service, University of Birmingham).Sequencing libraries prepared with the TruSeq Stranded Total RNA kit (Illumina Inc), from 1ug total RNA. Alignment of raw sequence reads to the human transcriptome (hg38) was performed via Rsubread and transcript abundance estimates were normalized and differentially expressed genes (DEGs) identified using a standard edgeR pipeline.

first: Christopher

last: McCabe

first: Martin

last: Read


title: Real-time quantitative PCR analysis of intestine of gilthead seabream

status: Public on Feb 07 2026

city: Almería

first: Alba

last: Galafat Díaz

state: Almería

address: Carr. Sacramento s/n

country: Spain

institute: University of Almería

summary: Anterior intestines were processed to extract RNA using the Total RNA Kit I (ENZA, Omega Bio-Tek), incorporating a Dnase tratment with the DNA free Kit (Rnase-Free Dnase I Set, Omea Bio-tek). Reverse transcription was performed using the RevertAid First Strand cDNA Synthesis Kit (Thermo Scientific #K1691). Real-time 1PCR amplifications were conducted in duplicates using a BIO-RAD CFX connect system (Bio-Rad Laboratories, Hercules) on 384-well-plates.

overall_design: qPCR gene epression profiling. The intestines of four fish per tank were used and treated separately as indicated in the summary.

first: A

last: Barany

first: J

last: Martos-Sitcha


title: Independent validation of circulating microRNAs as biomarkers in a case-control study of adolescents with type 1 diabetes for more than 8 years

city: Vienna

first: Matthias

last: Hackl

state: Austria

address: Leberstrasse 20

country: Austria

institute: TAmiRNA GmbH

summary: MicroRNAs (miRNAs) are epigenetic regulators of gene activity. Analysis of circulating miRNAs enables minimal-invasive studies of disease mechanisms and identification of novel disease biomarkers. The aim of this case-control validation study was to investigate previously identified circulating miRNAs in Swedish adolescents with long-duration (8.0–16.5 years) type 1 diabetes (T1D), and healthy matched controls to confirm their utility as biomarker candidates to diagnose and monitor the progression of T1D. Quantitative PCR analysis of 23 previously reported miRNAs was performed in 24 T1D and 24 control individuals. Body composition was assessed by dual-energy X-ray absorptiometry and peripheral quantitative computed tomography. Prospectively collected clinical data were retrieved from the Swedish diabetes quality registry. The selected miRNAs showed higher variability in both male and female T1D groups compared to controls. Statistical analysis confirmed differences for 12 miRNAs in comparison with controls, including miR-223-3p and miR-135a-5p, which previously were reported to be associated with T1D. MiR-34a-5p and miR-210-3p were positively associated with T1D duration and HbA1c (average from the last year), respectively. In conclusion, 12 previously reported miRNAs showed consistent differential expression between individuals with T1D and controls. Among these were miR-223-3p and miR-135a-5p, which are associated with cardiovascular/inflammatory disease and cancer, respectively.

overall_design: Quantitative PCR (qPCR) expression profiling of plasma microRNA. Analysis of 23 previously reported miRNAs was performed in 24 T1D and 24 control individuals.

first: Diana

last: Swolin-Eide

first: Auste

middle: P

last: Lycka

first: Gun

last: Forsander

first: Daniel

last: Novak

first: Johannes

last: Grillari

first: Andreas

last: Diendorfer

first: Per

last: Magnusson


title: Ketone body β-hydroxybutyrate restores Tau proteostasis via metabolism-independent mechanism

city: La Jolla

first: Leigh-Ana

last: Rossitto

address: 9500 Gilman Drive

department: Neurosciences

institute: UC San Diego

summary: Alzheimer’s disease (AD) and related tauopathies are marked by brain accumulation of pathological Tau aggregates and associated metabolic dysfunction. Metabolic interventions including ketogenic diets, caloric restriction, and exercise have shown promise in ameliorating cognitive impairments in AD, but variable efficacy and issues of compliance and side effects mar their translational potential. A shared molecular feature between these interventions is the induction of ketosis, a metabolic state marked by elevated circulating levels of β-hydroxybutyrate (βHB). Previous studies show βHB administration directly or in the form of a precursor can reproduce and even improve upon the benefits of metabolic interventions, but the molecular mechanism underlying the neuroprotective properties of βHB in AD remains to be elucidated. In the current study, we find that a βHB precursor diet is sufficient to ameliorate Tau pathophysiology in the PS19 mouse model at both the pathological and single-cell levels. This GEO record is for the hippocampal single nucleus RNA sequencing data generated for our diet paradigm.

overall_design: Male mice, either PS19 hTau+ or WT littermate controls, were switched from standard vivarium chow to either a ketone ester diet (KE) or a macro-controlled diet (CTL) at six months of age until about 9.5 months of age. At this time, mice were perfused with cold PBS, and hippocampi were dissected on ice, flash frozen, and stored at -80C until nuclei extraction. Three mice per group were included in this sequencing experiment for a total of 12 samples.

middle: M

first: Jamie

last: Foo

first: Julia

last: Di Silvestri

first: Leanne

last: Lehmann

first: Melina

last: Brunelli

first: Yuhang

last: Nie

last: Muñoz-Mayorga

first: Suborno

last: Jati

first: Qiang

last: Xiao

first: Anna

last: Dai-Liu

first: Meghan

last: Rossi

first: Richard

last: Daneman

first: Jeffery

middle: W

last: Kelly

first: John

middle: C

last: Newman

first: Samuel

last: Myers

first: Xu

last: Chen


title: Nerve Growth Factor (NGF) drives ILC2 pro-tumoral functions - bulk RNA sequencing of human TRKA+ and TRKA- ILC2s

city: Lausanne

first: Tania

last: Wyss

address: Rue du Bugnon 25A

country: Switzerland

institute: SIB Swiss Institute of Bioinformatics

summary: ILC2s are key regulators of tissue homeostasis and inflammation. In cancer, ILC2s can exhibit pro-tumoral functions by increasing the MDSC/T-cell ratio. Nevertheless, the upstream ILC2 triggers remain poorly defined. Here, we identify NGF as the driver of ILC2 pro-tumoral functions in bladder cancer patients. We show that ILC2s express the NGF receptor TrkA and respond to NGF by secreting type-2 cytokines. In the tumor microenvironment, NGF-producing mast cells accumulate and activate ILC2s to induce Tregs, ultimately fostering tumor growth. In patients, NGF levels inversely correlate with survival in ILC2-rich tumors, underscoring the clinical significance of this axis. In vivo administration of a selective TrkA inhibitor improves survival in orthotopic tumor-bearing animals and sensitizes them to immune checkpoint blockade (ICB). Overall, we identify NGF as a novel ILC2 activator that shapes pro-tumoral ILC2 functions. The blockade of TrkA+ ILC2s might represent a targetable strategy to improve survival, particularly in ICB-resistant patients.

overall_design: To uncover transcriptomic differences between TrkA+ and TrkA- ILC2s, we sorted these two subpopulations from PBMCs of three healthy donors and performed bulk RNAseq.

first: Maryline

last: Falquet

first: Sara

last: Trabanelli

first: Alejandra

last: Gomez-Cadena

first: Ziyang

last: Su

first: Camilla

last: Jandus


title: Single-nucleus RNA-seq results of AR-97Q and AR-24Q mice at 8 weeks of age.

first: Tomoki

last: Hirunagi

summary: To understand the early pathogenesis of motor neuron degeneration in spinal and bulbar muscular atrophy (SBMA), we conducted single-nucleus RNA-seq (snRNA-seq) on the spinal cords of AR-97Q and AR-24Q mice at 8 weeks of age. REST target genes were up-regulated in motor neurons of AR-97Q mice.

overall_design: snRNA-seq was conducted on spinal cord samples from AR-97Q and AR-24Q mice at an early stage (8 weeks of age). Spinal cords from three mice were pooled per sample for homogenization and nuclear isolation.

first: Kentaro

last: Sahashi

first: Madoka

last: Iida

first: Masahisa

last: Katsuno


title: Extracellular Small RNAs in Breast Milk: Molecular Profiles and Biological Implications

city: Wilmington

first: Uciel

last: Chorostecki

state: Delaware

address: 251 Little Falls Drive

institute: Kresko RNA Tech

type: Non-coding RNA profiling by high throughput sequencing

summary: Small RNA sequencing of human and bovine milk revealed abundant tRNA-, yRNA-, and rRNA-derived fragments. These exRNAs were validated and shown to promote cell survival under stress, suggesting a functional role in milk’s biological effects.

sample_organism:
Homo sapiens
Bos taurus

platform_organism:
Homo sapiens
Bos taurus

overall_design: Skim milk samples were collected from healthy humans (n=3) and cows (n=3). RNA was extracted and sequenced with Illumina TruSeq Small RNA libraries on a NovaSeq. Reads were quality filtered, aligned to curated sRNA references, and analyzed with custom scripts.

first: Clara

last: Claus

first: Carla

last: Borini Etichetti

first: Bruno

last: Costa

first: Julieta

last: B. Grosso

first: Juan P

last: Tosar

first: Silvana V

last: Spinelli


title: Activating GCN2 and subsequently the Unfolded Protein Response with the small oral molecule NXP800 delays tumor growth in osteosarcoma.

status: Public on Feb 05 2026

city: Nantes

first: Anaïs

last: Postec

address: 1 Rue Gaston Veil

institute: Nantes University

summary: Osteosarcoma (OS) is the most common primary malignant bone tumor mainly affecting children and young adults. Despite current treatments combining polychemotherapy and surgery, survival rates have remained unchanged for decades, highlighting the need to identify novel therapeutic approaches. NXP800, a newly developed orally available molecule, represents a promising therapeutic option. The therapeutic efficacy of NXP800 was evaluated in vitro and in a preclinical murine xenograft model of OS. RNA-seq analysis and functional assays were conducted to investigate the mechanisms of action and molecular target of NXP800. NXP800 decreases the viability of OS cell lines by blocking proliferation and inducing apoptosis. Mechanistically, NXP800 activates the Unfolded Protein Response (UPR), as demonstrated by eIF2α phosphorylation and ATF4 upregulation. This effect is mediated through the engagement of the Integrated Stress Response (ISR) via the activation of GCN2 kinase. Inhibition of GCN2, either through molecular or pharmacological approaches, abolishes NXP800-induced eIF2α phosphorylation and partially restores OS cell viability. Furthermore, NXP800 activates the IRE1α/JNK/c-Jun pathway while increasing the expression of the pro-apoptotic protein Puma. Finally, NXP800 delays tumor growth in preclinical OS model by promoting apoptosis. This study is a preclinical proof-of-principle of therapeutic efficacy of NXP800 both in vitro and in vivo, highlighting the relevance of targeting GCN2, and consequently activating the ISR and UPR, to induce apoptosis and inhibit tumor progression in OS.

overall_design: mRNA differential expression between HOS-MNNG cells treated or not with NXP800, at 6h or 24h after treatment..

first: Emma

last: Racineau

first: Morgane

last: Lallier

first: Jérôme

last: Amiaud

first: Rose-Anne

last: Thépault

first: Régis

last: Brion

first: Séverine

last: Battaglia

first: Céline

last: Charrier

first: Marie-Anne

last: Colle

first: Bénédicte

last: Brounais-Le Royer

first: Marc

last: Baud’huin

first: Franck

last: Verrecchia

first: Benjamin

last: Ory

first: Steven

last: Georges

first: François

last: Lamoureux


title: Transcriptomic profiling of co-cultured cancer-host cells identifies hypoxia as a driver of the skeletal muscle cell’s antiproliferative effect on cancer cells

city: Oslo

first: Jerome

last: Ruzzin

address: Sognsvannveien 9

department: Dept. of Molecular Medicine, Section of Biochemistry

country: Norway

institute: University of Oslo

summary:
Cancer metastasis is the leading cause of cancer-related death. While organs such as the lung are hotspots for metastases, others
-like skeletal muscle- remain rarely colonized, a phenomenon that remains poorly understood. In this study, we show that EO771
breast cancer cells proliferated robustly when co-cultured with MLg lung stromal cells, whereas their proliferation was restrained
when maintained in direct contact with differentiated C2C12 skeletal muscle myotubes. Notably, these effects were not cell-typespecific, as similar results were obtained with 4T1 breast cancer cells and Sol8 myotubes. After two days of co-culture, both cancer and host cells (MLg and C2C12) exhibited distinct niche-specific transcriptional remodeling. Strikingly, the poorly proliferative
EO771 cells co-cultured with C2C12 myotubes acquired a hypoxia-associated gene-expression signature despite normoxic
conditions (~20% O₂), showing that muscle cells reprogram cancer cells into a hypoxic, anti-proliferative state. Under hypoxic
conditions, we confirmed that the depletion of oxygen allows C2C12 cells to nearly abolish EO771 proliferation. Neither exogenous
lactate, culture acidosis, their combination, altered glucose levels, nor conditioned medium could reproduce the suppressive
environment created by C2C12 myotubes. In contrast, MLg cells induced minimal transcriptional changes in EO771 cells and were
themselves broadly reprogrammed by the cancer cells. Moreover, hypoxia enhanced EO771 proliferation in MLg co-cultures,
emphasizing the permissive nature of the MLg environment. Collectively, these findings uncover a unique, paradoxical, muscleinduced
pseudo-hypoxic program that restricts cancer cell proliferation. They also highlight the need for caution in targeting
hypoxia signaling in anti-metastatic therapies, as such interventions could weaken skeletal muscle’s natural defense against tumor
colonization.

overall_design: RNAseq profie of a co-culture model in which EO771 breast cancer cells  are maintained directly on either MLg cells or C2C12 myotubes,

first: Anine

last: Aunan

first: Charlotte

last: Claeyssen

first: Mohamed

last: Abelhalim


title: RNA-seq of sipinal cord of AR-97Q and WT mice at P7 and 13 weeks of age

first: Tomoki

last: Hirunagi

summary: Antisense oligonuleotides targeting human AR (AR-ASO) or Rest4 (Rest4-ASO) are intracerebroventriculary injected to AR-97Q mice at postnatal day 1 (P1). Gene expression profiles were analysed in the spinal cord of WT and AR-97Q mice at P7 and 13 weeks of age.

overall_design: RNA-seq analysis was performed in the mouse spinal cord at P7 (WT vs. AR-97Q vs. AR-ASO treated AR-97Q, Scramble-ASO vs. Rest4-ASO treated AR-97Q) and 13 weeks of age (WT vs. AR-97Q).

first: Kentaro

last: Sahashi

first: Masahisa

last: Katsuno


title: Comparative analysis of the transcriptomic response to cisplatin in drug-sensitive and drug-resistant testicular germ cell tumors.

city: Urbana

first: Mehwish

middle: Wahid

last: Khan

state: Illinois

address: 2001 S Lincoln Ave

department: Department of Comparative BioSciences

institute: University of Illinois Urbana-Champaign

summary: Testicular germ cell tumors (TGCTs) are uniquely curable with cisplatin-based therapies even when widely metastatic, however cisplatin resistance does occur resulting in very poor prognosis. The mechanisms to explain TGCT hypersensitivity to cisplatin and mechanisms of resistance are not well understood. The global transcriptional response to acute cisplatin treatment (24 hours after a 6-hour pulse of cisplatin) was assessed in three parental embryonal carcinoma TGCT cells lines compared to multiple isogenic, stable, cisplatin-resistant clonal lines from these pa-rental cells.  Cisplatin treatment of parental cells consistently showed a more robust overall transcriptional response to cisplatin compared to their cisplatin-resistant cellular counterparts for a common set of genes and pathways including the upregulation of genes associated with histone modifications and p53, EMT, and KRAS signaling and the downregulation of genes normally upregulated by MYC. Focusing on genes exclusively altered in parental cells revealed upregulated genes known to be induced by p53 and downregulated by MYC and the transferrin receptor, TFRC1. Several of these p53/MYC/TFRC1 targets were associated with a higher instance of disease free survival in a cohort of TGCT patients. Cisplatin resistance in TGCT cells is associated with a diminished alteration of cisplatin responsive genes especially genes known the be regulated by p53, MYC and TFRC1 that may be linked to cisplatin hypersensitivity and survival in TGCTs.

overall_design:
This study represents a reanalysis of RNA-seq data combining newly generated cisplatin treated testicular germ cell tumor(TGCT) samples with the previously submitted untreated control samples. Newly submitted samples correspond to cisplatin sensitive TGCT cells and their derived resistant cells treated with Cisplatin. Untreated control samples (GSM3720309 - GSM3720311,GSM3720315-GSM3720320 and GSM3720333-GSM3720350) were obtained from the existing GEO Series GSE129696  and are not resubmitted. All FASTQ files were aligned to human genome assembly NCBI GRCh38 using STAR aligner, the resulting BAM files were summarized to genes using the featureCounts algorithm. The processed files contains the TMM normalized log counts per million (log CPM) values for each Sample,(treated and untreated both).

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

middle: J

last: Spinella


title: IL1A enhances TNF-induced retinal ganglion cell death

status: Public on Feb 04 2026

city: Bar Harbor

last: MacLean

state: ME

address: 600 Main Street

institute: The Jackson Laboratory

summary: Introduction: A growing body of literature suggests a role for neuroinflammation in retinal ganglion cell (RGC) death in glaucoma. For instance, deficiency of three proinflammatory cytokines, complement component 1, subcomponent q (C1q), interleukin 1 alpha (Il1a), and tumor necrosis factor (Tnf), resulted in significant protection of RGCs after glaucoma-relevant insults. While TNF and C1Q have been extensively investigated in glaucoma-relevant model systems, the role of IL1A in RGCs is not well defined.  Methods: Eyes of 2-4 month-old C57BL/6J mice or mice deficient in either Jun or Sarm1 were intravitreally injected with IL1A alone, TNF alone, or IL1A and TNF together. Retinal flat mounts were assessed for RGC survival using immunostaining of RBPMS. Bulk RNA-sequencing and differential expression analyses of retinal tissue was performed to determine molecular changes in response to IL1A, TNF, and IL1A combined with TNF within C57BL/6J and Sarm1 deficient mice.  Results: Intravitreal injection of IL1A did not result in RGC death at either 14 days or 12 weeks. Consistent with previous studies, TNF injection did not cause significant RGC loss at 14 days but did after 12 weeks. Together, IL1A+TNF resulted in a relatively rapid RGC death, driving significant loss two weeks after injection. We identified molecular changes which occur in response to IL1A and to combined IL1A+TNF treatment with limited changes identified in TNF alone treated eyes. Using mice deficient in Jun or Sarm1, we showed RGC loss after IL1A+TNF insult is JUN-independent and SARM1-dependent. Furthermore, RNA-seq analysis showed Sarm1 deficiency does not stop the neuroinflammatory response to IL1A+TNF.  Discussion: We identified a novel role of IL1A, we found that IL1A acted as a sensitizer to TNF-induced death. Co-injection of IL1A and TNF resulted in rapid RGC death, with significant RGC loss 14 days after injection. TNF+IL1A-induced RGC death did not depend on JUN activation and was rather SARM1 dependent.  Also, RNA-seq analyses indicated that while Sarm1 deficiency protected from IL1A+TNF induced RGC loss it did not significantly alter microglia and astrocyte responses. Altogether, these findings indicate that IL1A potentiates SARM1-dependent TNF-induced RGC death in vivo.

overall_design: Eyes of 2-4 month-old C57BL/6J mice or mice deficient in either Jun or Sarm1 were intravitreally injected with IL1A alone, TNF alone, or IL1A and TNF together.  Retinas were dissected after 2, 14, or 35 days and subjected to tissue processing and RNA-sequencing.

first: Katherine M.

last: Andersh

first: Gareth R.

last: Howell

first: Richard T.

last: Libby


title: Environmental Amino Acid Sensing Regulates the Rate of ASC Translation and NLRP3 Inflammasome Assembly

city: Philadelphia

first: Montana

last: Knight

state: PA

address: 3615 Civic Center Blvd

department: Department of Biomedical and Health Informatics

institute: Children's Hospital of Philadelphia

summary: The NOD-, LRR-, and pyrin domain-containing protein 3 (NLRP3) inflammasome is a multiprotein signaling complex that triggers pyroptotic cell death and interleukin (IL)-1 family cytokine release during infection and cell injury. Its assembly is driven by the adaptor protein, apoptosis-associated speck-like protein containing a CARD (ASC), whose filamentation forms a supramolecular speck upon NLRP3 activation to amplify inflammasome signaling. While the NLRP3 inflammasome is well appreciated as a sensor of environmental danger and damage, little is known about how homeostatic environmental factors like dietary metabolites regulate its activity. Here, we find that environmental availability of the branched-chain amino acids (BCAAs), leucine, isoleucine, and valine, controls NLRP3 inflammasome assembly. While ASC is typically viewed as a constitutively expressed, unregulated inflammasome component, we find that Toll-like receptor 4 (TLR4) activation triggers localization of ASC mRNA to the perinuclear space. Moreover, our data demonstrate that ASC undergoes TLR4-driven translational bursting from polyribosomes during inflammasome priming. This translational engagement is dependent on BCAA availability and mechanistic target of rapamycin (mTOR) activity, which regulate the kinetics of inflammasome assembly. In contrast, the translation of NLRP3 and caspase-1 is largely insensitive to these inputs. Furthermore, we find that BCAAs regulate NLRP3 inflammasome activation in both mouse and human macrophages, in the context of bacterial infection, and during lipopolysaccharide (LPS)-induced sepsis in vivo. Altogether, this work unveils a novel inflammasome priming event governed by the amino acid environment. These findings further highlight how the activity of proteins maintained in equilibrium like ASC can be dynamically regulated through rapid changes in mRNA translation.

overall_design: Mus musculus macrophage samples stimulated with LPS in either normal control media or undergoing a torin treatment. RNAsequencing data collected examining both total and polysomal RNA in the samples. Three samples per group.

first: Mikel

middle: D

last: Haggadone

first: Brian

last: Goldspiel

first: Aoife

last: O’Farrell

first: Nora

middle: T

last: Kiledjian

first: Talia

middle: R

last: Smith

first: Elena

last: Anderson

first: Víctor

last: Vázquez Marrero

first: Mark

last: Boyer

first: Peining Jimmy

last: Xu

last: Scaglione

first: Zachary

last: Powers

first: Clemence

last: Queriault

first: Aaron

last: Wu

first: Qihua

last: Yang

first: Mary

middle: X

last: O’Riordan

first: Arjun

last: Raj

first: Clementina

last: Mesaros

first: Crystal

middle: S

last: Conn

first: Sunny

last: Shin

first: Will

last: Bailis


title: CFP1-mediated H3K4me3 broad domains control early B cell lineage fate determination [4C-Seq]

city: Shenzhen

first: Wanyu

last: Bai

address: 628 Zhenyuan Road

institute: The Seventh Affiliated Hospital of Sun Yat-Sen University

summary: Histone H3K4me3 broad domain (BD) is a unique epigenetic feature to mark cell identity-associated genes, but its physiological role in lineage differentiation remains unclear. Here we show that CFP1, an integral component of the Setd1A/B methyltransferase complex, is critically required for functional H3K4me3-BD installation and B cell fate determination. Cfp1 deletion impairs H3K4me3-BDs on a subset of B-lineage genes and redistributes H3K4me3 from active genes to bivalent promoters. Transcription of subsets of H3K4me3-BD-bound gene is diminished in part due to reduced RNA Pol II at the promoter and gene body. Specifically, CFP1 ablation abolishes H3K4me3-BD at the recombination center and distal PAIR elements in the immunoglobulin heavy chain (IgH) gene, severely compromises its locus contraction for efficient V-to-DJ recombination and consequently arrests cells at the pro-B stage. Moreover, Cfp1-deficient pro-B cells upregulate a panel of progenitor and myeloid-specific genes with elevated H3K4me3 marks and can trans-differentiate into various myeloid cell types. Therefore, our study reveals pivotal roles for CFP1-mediated H3K4me3-BDs in the transcriptional regulation of cell lineage fate specification and commitment.

overall_design: We performed CUT&Tag, ChIP-seq, RNA-seq, V(D)J-HTGTS and 4C-HTGTS in murine pro-B cells to study roles of CFP1-regulated epigenetic program in early B cell development.

first: Yalin

first: Yanan

last: Zhao

first: Shuoxu

last: Gong

first: Yimiao

last: Lu

first: Zhonghui

last: Xue

first: Lie

last: Wang

first: Fei-Long

last: Meng

first: Chun

last: Chen

first: Junchao

last: Dong


title: V gamma 1  gamma-delta T cells steer airway macrophages towards a pro-fibrotic response in an autochthonous lung cancer mouse model  [scRNA-Seq]

city: Glasgow

first: Robin

last: Shaw

address: Switchback Road

country: United Kingdom

institute: CRUK Scotland Institute

summary: Gamma-delta T cells are important for host defence at the respiratory mucosa, acting directly or through interactions with other cells. However, how Gamma-Delta T cells influence other immune cells in the lung remains unclear. Using a genetically engineered mouse model of lung cancer, we show that tumours drive expansion of both CD27+ and CD27— Gamma-Delta T cells. Advanced microscopy techniques indicated that CD27— Gamma-Delta T cells are enriched in tumours, while CD27+ Gamma-Delta T cells are more prone to interact with macrophages in tumour-associated adventitial cuffs. SiglecFlow pro-fibrotic airway macrophages were more prevalent in lung tumour-bearing mice than tumour-free mice. This pro-fibrotic subset was reduced in lungs when the cancer model was crossed to Tcrd knockout mice or treated with V Gamma1-depleting antibodies, but not in TcrgV4/6 knockout mice. Thus, our findings implicate V Gamma1 Gamma-Delta T cells in driving tumour-associated airway macrophage functional imprinting. Determining the translatability to human health may offer new avenues for refining patient management and immunotherapeutic strategies.

overall_design: Lung tissue from Mus musculus was extracted, and three distinct regions were sampled: tumour tissue, tumour-distant tissue, and normal tissue. Macrophages were isolated from each sample using flow cytometry. The sorted cell populations were then sequenced using the 10X Genomics Chromium Single Cell 3′ protocol.

first: Ximena L.

last: Raffo-Iraolagoitia

first: Amanda J.

last: McFarlane

first: Sarah

last: Laing

first: Ryan

last: Corbyn

first: Lindsey W. G.

last: Arnott

first: Frédéric

last: Fercoq

first: Lynn

last: McGarry

first: Judith

last: Secklehner

first: Marco

last: De Donatis

first: John B. G.

last: Mackey

first: Bjorn

last: Kruspig

first: Robert

last: Wiesheu

first: Ya-Ching

last: Hsieh

first: Kai

last: Rakovic

first: John

last: Le Quesne

first: Graeme

last: Clark

first: Colin

last: Nixon

first: Crispin

last: Miller

first: Kristina

last: Kirschner

first: Calum C.

last: Bain

first: Daniel J.

last: Murphy

first: Seth B.

last: Coffelt

first: Leo M.

last: Carlin


title: Discovery and Evaluation of Biomarkers for Triple-Negative Breast Cancer Subtypes Uncovers Patient Stratification and Targeted Therapeutic Strategies

city: Badalona

first: David

last: Olivares

state: Select One

address: Ctra de Can Ruti, Camí de les Escoles s/n 08916 Badalona, Barcelona

institute: Josep Carreras Research Instiute

summary: Triple-negative breast cancer (TNBC) is the most heterogeneous and aggressive subtype of breast carcinoma, defined by the absence of clinical biomarkers and the lack of targeted therapies. Despite numerous clinical trials, patient stratification remains suboptimal, limiting the identification of effective treatment strategies. In this study, we aimed to identify biomarkers exclusively expressed in the basal mammary epithelial compartment to refine TNBC subclassification. Through computational analysis of single-cell RNA sequencing data, we defined a set of basal identity genes, which were subsequently validated by immunohistochemistry in two independent TNBC cohorts. This approach enabled the identification of a novel TNBC subgroup, termed true basal TNBC (tB-TNBC), associated with poorer prognosis and distinct molecular features. To uncover therapeutic vulnerabilities in this subgroup, we conducted a high-throughput screen of 3,200 FDA-approved compounds in breast cancer cell lines classified by basal marker expression. This analysis identified dasatinib as a promising candidate with selective activity against tB-TNBC models. Furthermore, TAGLN emerged as a strong predictive biomarker of dasatinib response, with functional studies confirming its role in modulating drug sensitivity. Altogether, these findings support the clinical utility of basal markers for TNBC stratification and highlight a targeted treatment opportunity for tB-TNBC patients.

overall_design: Total RNA was extracted using the NZY miRNA Isolation & RNA Clean-up Kit (MB13402, NZYtech) following the manufacturer’s protocol. The purity and concentration of the RNA from each sample were assessed using an Agilent TapeStation with an RNA ScreenTape Analysis Kit. mRNA enrichment was subsequently performed using polyA-tail-connected magnetic beads and oligos. This was followed by double-stranded DNA synthesis and polymerase chain reaction (PCR) amplification using specific primers. The PCR products were subjected to thermal denaturation to produce single-stranded DNA, which was cyclized into a circular DNA library using bridge primers. Sequencing was conducted using the DNBSEQ platform (BGI Genomics Co.). Raw sequencing data were preprocessed using SOAPnuke software (BGI Genomics Co.). This involved removing reads with adaptor contamination, more than 5% N content, and low-quality reads (where more than 20% of the bases had a quality score below 15). The resulting "Clean Reads" were saved in FASTQ format. RNA-seq data were analyzed using the Galaxy workbench platform [33], adhering to specific recommendations [34]. Quality control and trimming of the reads were performed using MultiQC [35] and Cutadpt [36]. The reads were then mapped to the reference genome (Hg38, human genome build 38) using STAR [37]. From the mapped sequences, the number of reads per annotated gene was counted using featureCounts [38]. Subsequently, DESeq2 [39] was used to normalize the read counts and identify differentially expressed genes. Functional enrichment analysis of differentially expressed genes was performed using GSEA [40]

first: D

last: Ortega-Álvarez

last: Olivares-Osuna

first: V

last: Rodilla


title: Multiple defects in mouse stem cell based embryo models lacking all Hox function [scRNA-seq]

city: Paris

first: Hocine

last: Rekaik

address: 11, Place Marcelin Berthelot

department: CIRB

institute: College de France

summary: Mammals have four genomic copies of an ancestral Hox cluster, with a total of 39 genes. While gene inactivation approaches and full cluster deletions have revealed their critical functions during early development, the effect of removing all Hox function has remained elusive due to both biological and technological challenges. We have used mouse gastruloids, an ES cells-derived embryo model where Hox genes are properly activated in time and space, to assess the effect of their complete absence. We report that gastruloids lacking Hox function can still elongate and reach a general shape resembling their control counterparts, with a well-established AP polarity. However, unlike controls, they fail to produce any endoderm and are unable to properly segment their presomitic mesoderm into persistent somite-like structures. Instead, they produce a type of mesoderm with a more anterior identity. We thus propose that, in this system at least, HOX proteins are necessary to posteriorize an existing anterior ‘ground-state’ structure, in part by promoting and/or maintaining the epithelialization of cellular condensations. Multiomes analysis revealed range of modifications in chromatin accessibility in the absence of any HOX proteins, involving in particular variations in the binding of the co-factor PBX1. In contrast, neuro-mesodermal progenitor (NMP) cells are not overtly affected in mutant gastruloids, even though they normally initiate strong Hox gene transcription, suggesting that these cells are used as vehicles to translate a temporal sequence of activation into an AP colinear transcript distribution, which becomes functional at a later stage only.

overall_design: scRNA-seq of wt and Hox-/- gastruloids at 72, 96 and 120h

first: Lucille

last: Lopez-Delisle

first: Alexandre

last: Mayran

first: Yuliia

last: Romaniuk

first: Cynthia

last: Diabanza

first: Anne-Catherine

last: Cossy

first: Denis

last: Duboule


title: Dopamine Enhances Surface Glial Glycolysis via Acetylcholine and Insulin/Insulin-Like Growth Factor Signaling in Honeybee

status: Public on Feb 03 2026

city: Changchun

first: Miaoran

last: Zhang

state: Jilin

address: Xinmin Street

institute: Department of Physiology, College of Basic Medical Sciences, Jilin University

summary: Glycolysis plays a crucial role in maintaining neuronal functional homeostasis and is regulated by neuroendocrine signals, particularly dopamine. However, the underlying regulatory mechanisms remain poorly understood. Here, we investigate dopamine driven neuroendocrine control of glial glycolysis in honeybee through integrated metabolomics and single-cell transcriptomics. Activation of dopamine 2 receptors(D2R) via bromocriptine significantly enhanced glycolytic flux in worker bees, as evidenced by elevated glucose levels, accumulation of glycolytic intermediates, and suppression of pentose phosphate pathway metabolites. Single-cell and single-nucleus RNA sequencing revealed that acetylcholine (ACh) secreted by Kenyon cells (KCs) is a critical node in dopamine-regulated glycolysis. Bromocriptine treatment reduced ACh secretion and directly enhanced surface glial (SG) specific glycolytic gene expression, while also increasing insulin signaling from cortex glial to surface glial. Our findings uncover a dual regulatory mechanism, in which the dopamine-ACh axis coordinates with IIS signaling to orchestrate metabolic plasticity in glial through cell type-specific precision. This study provides insights into how social insects integrate neuroendocrine signals to optimize energy metabolism and highlights the role of ACh in this process.

overall_design: We employed single-nucleus RNA sequencing (snRNA-seq) using the 10x Genomics platform to investigate the effects of bromocriptine, a dopamine agonist, on the neural transcriptome of honeybee (Apis mellifera) forager brains. For this study, foraging bees were divided into two experimental groups: one treated with bromocriptine and the other with water as a control. Brains from 15 foragers per group were dissected and processed for snRNA-seq to resolve cell-type-specific transcriptional responses. This work represents the first application of single-nucleus transcriptomics to explore neuropharmacological modulation in honeybees, offering unprecedented insights into how dopaminergic signaling influences neural plasticity and foraging-related behaviors in a eusocial insect model. By comparing bromocriptine-exposed and control groups, our findings may advance understanding of conserved neuromodulatory pathways and their roles in social insect behavior

first: Peng

last: Chen

first: Xingan

last: Li


title: RNA sequeqncing data of Kat6a–/–, Kat6a+/– and Kat6a+/+ E12.5 dorsal telencephalon and of Kat6a+/– and Kat6a+/+ E16.5 cortical neurons

city: Parkville

first: Nishika

last: Ranathunga

state: VIC

address: 1G Royal Parade

country: Australia

institute: Walter and Eliza Hall Institute of Medical Research

summary: Mutation of one allele of the KAT6A gene encoding the histone acetyltransferase KAT6A (MOZ, MYST3) causes Arboleda-Tham-Syndrome (ARTHS), which is characterised by developmental delay, cognitive impairment and autism-like behaviours.  We used mice to examine the effects of  Kat6a mutations on gene expression in the develping cerebral cortex and cortical neurons. We examined the effects of homozygous and heterozygous loss of Kat6a on gene expression in the E12.5 dorsal telecencephalon, the embryonic precursor of the cerebral cortex, and the effects of heterozygous loss of Kat6a on gene expression in foetal cortical neurons.

overall_design: N = 4 Kat6a–/– vs. 4 Kat6a+/+ E12.5 dorsal telencephalon; 4 Kat6a+/– vs. 4 Kat6a+/+ E12.5 dorsal telencephalon; 4 Kat6a+/– vs. 4 Kat6a+/+ E16.5 cortical neurons

first: Alex L

last: Garnham

first: Samatha

last: Eccles

first: Anne K

last: Voss

first: Tim

last: Thomas


title: Loss of PIK3CA allows in vitro growth but not in vivo progression of KRAS mutant lung adenocarcinoma in a syngeneic orthotopic implantation model

status: Public on Feb 02 2026

city: Stony Brook

first: Harold

last: Bien

state: NY

address: 100 Nicolls Road

institute: Stony Brook University

summary: Constitutively active KRAS mutations are highly prevalent in lung cancers, but the direct role of its downstream phosphatidylinositol 3-kinase (PI3K) pathway in tumor progression remains unclear. A previous study established the requirement for PIK3CA, the alpha catalytic isoform, in lung tumor development in mouse models with an intact Trp53 tumor suppressor. In this study, we further investigated the requirement for PIK3CA for tumor growth both in vitro and in vivo. We first generated a “KPA” cell line by genetically deleting Pik3ca from a murine lung adenocarcinoma “KP” cell line harboring oncogenic KrasG12D and lacking Trp53. We found that Pik3ca is not required for cell survival and growth in vitro, even under anchorage-independent conditions but reduced the growth rate by 20%. We next orthotopically implanted KP and KPA cells into syngeneic mice and found that PIK3CA is absolutely required for tumor progression, even in the absence of Trp53. Implantation of KP cells, or a “KPS” cell line lacking the Stk11 gene, led to rapid tumor growth and death of all host animals. In contrast, mice implanted with KPA cells all survived with no detectable lung tumors. The gene expression profiles from cultured cell lines suggest KPA cells may be vulnerable to oxidative stress. Indeed, we found KPA cells were more sensitive to hydrogen peroxide and diethyl maleate-induced oxidative stress as compared to KP and KPS cells. Together, these results demonstrate that PIK3CA is not required for lung cancer cell growth induced by mutant KRAS in vitro but is critically needed for in vivo progression and growth.

overall_design: Bulk RNA library preparation and sequencing of 3 biological replicates of cultured KP, KPA, and KPS was performed using a commercial supplier (Novogene, Inc.) with the NEBNext® Ultra™ II RNA Library Prep Kit for Illumina (New England Biolabs E7770L) with the Poly(A) mRNA Magnetic Isolation Module. Libraries were sequenced at a depth of approximately 33 million paired reads per sample (PE150) on an Illumina NovaSeq XPlus.

first: Abigail

middle: L

last: Booth

first: Giuseppe

last: Caso

first: Barbara

last: Rosati

first: Richard

middle: Z

last: Lin


title: Dual AAV gene therapy using laminin-linking proteins ameliorates muscle and nerve defects in LAMA2-related muscular dystrophy

city: Basel

first: Eleonora

last: Maino

address: Spitalstrasse 41

department: Biozentrum

institute: University of Basel

summary: Adeno-associated virus (AAV)-mediated gene replacement holds promise for treating genetic diseases but faces challenges due to AAV’s limited packaging capacity and potential immune responses to transgene products, especially in patients lacking endogenous protein. LAMA2-related muscular dystrophy (LAMA2 MD), a severe congenital disorder caused by loss of laminin-α2, presents both hurdles: the LAMA2 gene exceeds AAV capacity, and severely affected patients do not produce the native protein. Here, we developed an AAV-based therapy using two engineered linker proteins derived from endogenously expressed components. These linker proteins restore laminin receptor binding and polymerization, enabling reassembly of a functional basement membrane. Dual AAV delivery of the linkers in a severe LAMA2 MD mouse model resulted in robust expression and significant improvements in muscle histology and function. Employing myotropic capsids enabled therapeutic efficacy at lower vector doses. However, muscle-specific targeting unmasked a LAMA2-related peripheral neuropathy. To address this, we expressed one linker under a muscle-specific promoter and the other under a ubiquitous promoter, delivered via AAV9 or AAV8. This approach achieved near-complete phenotypic restoration when administered neonatally and provided significant benefit when given at progressed disease stages. Our strategy offers a mutation-independent, size-compatible, and potentially immune-tolerable treatment for LAMA2 MD with broad clinical potential.

overall_design: RNA-seq analysis of tibialis anterior (TA) muscle from 8-week-old mice: non-injected wild-type and dyW/dyW mice, and wild-type and dyW/dyW mice injected intravenously at P1 with AAV9-Spc/CBh-DL (1×10¹⁴ vg/kg per construct).

first: Judith

last: Reinhard

first: Lin

last: Shuo

first: Maino

last: Eleonora

first: Daniel

last: Ham

first: Markus

last: Rüegg


title: Novel Molecular Marker for Nociceptors

city: Solna

first: Saida

last: Hadjab

address: Solnavägen 9

department: Neuroscience

country: Sweden

institute: Karolinska Institutet

summary: Chronic pain affects approximately 20% of the global population and represents a major unmet medical need. Improved molecular characterization of pain-sensing neurons is essential for the development of more precise therapeutic strategies.

overall_design: Following tamoxifen injection DAPI+NeuN+ stained nuclei from dorsal root ganglia were isolated using fluoresence activate cell sorting (FACS) and analyzed using snRNA-seq.

first: Kaiwen

last: Zhang

first: Prach

last: Techameena


title: Single myonuclei RNA-seq on control vs AAV-OPDM mouse models

city: ILLKIRCH

first: Nicolas

last: Charlet-Berguerand

address: 1 rue Laurent Fries

institute: IGBMC

summary: We injected in WT BL6 male mice either NaCl (control) or AAV.MYO4A coding either for the GFP (control) of for ATG polyG-GFP, OPDM2 uGIPpolyG-GFP, OPDM3 uN2CpolyG-GFP or OPML LOC6polyG-GFP. These diverse polyGlycine proteins are responsible oculopharyngodistal myopathy (OPDM). Our aim was to determine through single nuclei RNA seq whether expression of these polyGlycine-proteins in muscle leads to a common and specific signature.

overall_design: Single nuclei RNA-seq analysis was performed using 10X Genomics FLEX multiplex technology which uses barcoded probe sets targeting the whole transcriptome and enabling sample multiplexing. Tibialis Anterior (TA), gastrocnemius and quadriceps muscles of 7 months post-AAV injection of two individuals per genotype : NaCl-, GFP-, ATG polyG-GFP-, uGIPpolyG-GFP-, uN2CpolyG-GFP- or LOC6polyG-GFP- injected mice.

first: Manon

last: Boivin


title: Multiple defects in mouse stem cell based embryo models lacking all Hox function [ATAC-seq]

first: Hocine

last: Rekaik

overall_design: ATAC-seq of wt and Hox-/- mES cells cultured under standard conditions.

first: Lucille

last: Lopez-Delisle

first: Alexandre

last: Mayran

first: Yuliia

last: Romaniuk

first: Cynthia

last: Diabanza

first: Anne-Catherine

last: Cossy

first: Denis

last: Duboule


title: Multiple defects in mouse stem cell based embryo models lacking all Hox function [RNA-Seq]

overall_design: RNA-seq of wt and Hox-/- mES cells cultured in 2D under standard conditions and subjected to an endoderm differentiation protocol, as well as RNA-seq of these cells used to generate Chiron- and Activin A–treated gastruloids.


title: Intraspecific variation in the duration of epigenetic inheritance in wild isolates of C. elegans

status: Public on Feb 01 2026

first: Germano

last: Cecere

address: Institut Pasteur, 28 Rue Du Docteur Roux, Batiment Monod, 5eme Etage

department: Development and stem cell biology

institute: Institut Pasteur

summary: Epigenetic inheritance is generally less stable across generations than DNA sequence-based heredity. One common form of epigenetic inheritance, found in plants, fungi, and animals, is the transgenerational memory of gene silencing mediated by small RNAs. These small RNAs can be amplified through RNA-dependent RNA polymerases, thus maintaining the silenced state across multiple generations. Such molecular mechanisms raise questions regarding their natural variation and evolutionary impact. We here ask whether the presence and duration of epigenetic inheritance vary within a species. We use the ability of the nematode Caenorhabditis elegans to silence genes for multiple generations after an initial RNA interference trigger. We find that the duration of silencing memory expressed in number of generations varies across C. elegans wild strains as a quantitative trait. Strikingly, several wild strains show no memory, while some display a longer memory than the reference strain. Natural DNA sequence polymorphisms, such as in the set-24 gene, affect the duration of small RNA inheritance. We further show that the silencing memory duration in wild strains increases with temperature and that memory is retained upon early starvation arrest and passage through dauer diapause. Altogether, these results demonstrate intraspecific diversity in the regulation of small RNA-based heredity, a prerequisite for selection acting on genetic variants affecting epigenetic inheritance duration.

overall_design: small RNA sequencing profiles of natural C. elegans isolate harboring a germline nuclear GFP reporter and subjected to RNAi silencing targeting the GFP reporter or control RNAi.

first: François

last: Frejacques

first: Marie

last: Saglio

first: Mohammed

last: Aljohani

first: Christian

last: Froekjaer-Jensen

first: Almira

last: Chervova

first: Loan

last: Bourdon

first: Lise

last: Frézal

first: Marie-Anne

last: Félix


title: Profiling of CSDE1-bound RNAs under MKRN2-mediated ubiquitination

city: Shanghai

first: Zi

last: Wang

address: 600 South Wanping Road, Xuhui District, Shanghai, China

institute: Shanghai Mental Health Center

summary: This study aims to elucidate how MKRN2-mediated ubiquitination regulates the RNA-binding capacity of CSDE1. By overexpressing CSDE1 in MKRN2 knockout (KO) SHSY5Y cells and complementing with MKRN2 for comparison, we systematically analyzed the alterations in the RNA-binding repertoire of CSDE1 upon its interaction with MKRN2.

overall_design:
Objective: Identify RNAs whose binding to CSDE1 depends on MKRN2.
Approach: RNA immunoprecipitation from MKRN2 KO cells subjected to:
1. Control: Empty vector transfection.
2. CSDE1-OE: CSDE1 overexpression alone.
3. Rescue: Co-expression of CSDE1 and MKRN2.
Outcome: Comparison of bound RNAs across conditions will reveal MKRN2-dependent targets.

first: Min

last: Zhu

first: Ronggui

last: Hu


title: Spatial transcriptomics Reveals Impact of APOE4 Allele on α-Synuclein Aggregation and Cell-Cell Communication in Lewy Body Dementia

city: Jacksonville

last: Zhao

state: FL

address: 4500 San Pablo Rd S

institute: Mayo Clinic

summary: We performed spatial transcriptomics to understand a-synuclein pathology-specific molecular profiles and cell-cell communication in human Lewy Body Dementia (LBD) brains. We included APOE3/3 and APOE3/4 LBD brains to dissect APOE4 impact on a-synuclein pathologies. Our analysis showed the key dysregulated pathways around the pathology comparing LBD brains to control brains, which further exacerbated by APOE4.

overall_design: To explore this, we conducted spatial transcriptomics using the 10X Genomics Visium CytAssist platform on Formalin-Fixed Paraffin-Embedded tissue slides from the temporal cortex of human LBD brains (N=4 control and N=6 LBD brains, with an equal ratio of APOE3/3 and APOE3/4 genotypes). We defined the neuronal layers of the gray matter (Layers 1 to 6, L1-6) and white matter (WM), and identified LBs from hematoxylin and eosin (H&E) staining to annotate LB-positive (LB+), LB-surrounding and LB-negative (LB-) spots in each brain. We evaluated gene signatures in each layer and analyzed cell-cell communication using the CellChat tool across the layers.

first: Yunjung

last: Jin

first: Alexander

middle: Q

last: Wixom


title: Multiple defects in mouse stem cell based embryo models lacking all Hox function

first: Hocine

last: Rekaik

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

overall_design: Refer to individual Series


title: Transcriptional profiling of tumor microenvironment in B2M KO CD40-treated B16 tumors implanted in mice

city: Boston

first: Amy

last: Huang

state: MA

address: 25 Shattuck St

department: Immunology

institute: Harvard Medical School

summary: The immune changes induced by loss of antigen presentation by tumor cells, a common mechanism of acquired resistance to immunotherapy, as well as the mechanisms by which CD40 agonist treatment controls the growth of B2m-null tumors, are unknown. We performed single-cell RNA-seq of total tumor-infiltrating immune cells in control and B2m-null tumors treated with isotype control or CD40 agonist antibodies to identify changes in immune cell states due to tumor cell loss of B2m and agonist CD40 treatment.

overall_design: C57BL/6J mice were implanted subcutaneously with 1 x 10^6 B2m-null or control Bro4.1 B16 cells. Mice were treated via intraperitoneal injection with either 100mcg anti-CD40 or rat IgG2a isotype control antibody on days 6, 9, and 12 post tumor implantation. Mice were euthanized on day 14, tumors harvested and immune cells isolated for single-cell RNA-sequencing. Prior to running on the 10x Chromium, cells from individual mice were stained with cell hashtag antibodies and then individual mice from each experimental group were mixed together to run on a single Chromium lane.

first: Matt

last: Zimmerman

first: Megan

last: Fung

first: Emily

last: Cox

first: Wan

last: Chong

first: Katherine

last: Vietor

first: Yacine

last: Choutri

first: Rose

last: Al Abosy

first: Nicholas

last: Haining

first: Debattama

last: Sen

first: Arlene

last: Sharpe

first: Brian

last: Miller


title: Integrated multi-platform metabolomics reveals fatty acid-mediated inflammatory signatures in pretibial myxedema

first: Jiayi

last: Cai

address: Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, 197 Ruijin 2nd Road

summary: Context: Pretibial myxedema (PTM) is a refractory autoimmune dermopathy associated with Graves’ disease. Although metabolic dysregulation has been recognized in thyroid-associated disorders, the metabolic profile and its functional role in PTM remain unclear. Objective: To characterize the metabolic landscape of PTM lesions and explore the contribution of fatty acids to fibroblast dysfunction and inflammation. Methods: We performed untargeted metabolomic profiling of PTM skin lesions and healthy controls using LC-MS and GC-MS, integrated with spatial metabolomics to localize metabolic changes. Functional assays were conducted by stimulating human foreskin fibroblasts (HFFs) with palmitic acid (PA) and oleic acid (OA), followed by RNA sequencing, cytokine assays, and immunohistochemistry. Results: PTM lesions exhibited substantial metabolic reprogramming, including accumulation of fatty acids and elevated tricarboxylic acid cycle intermediates. Spatial metabolomics confirmed pronounced lipid deposition in the dermis, the primary site of PTM pathology. RNA-seq of fibroblasts stimulated with PA and OA revealed enrichment of inflammatory pathways, including IL-17 and NF-κB signaling, and marked upregulation of IL-8 (CXCL8). Fatty acid stimulation induced robust IL-8 secretion, consistent with increased IL-8 expression in PTM lesions. Moreover, PA promoted α-SMA expression in fibroblasts, suggesting induction of myofibroblast differentiation. Conclusions: Our findings demonstrate that dermal fatty acid accumulation in PTM may contribute to fibroblast-mediated inflammation and fibrosis. This study provides novel insights into the metabolic-immunologic interface underlying PTM pathogenesis.

overall_design: Human foreskin fibroblasts (HFFs) were treated with Vehicle, Palmitic Acid (PA), or Oleic Acid (OA) to investigate the effect of fatty acids on fibroblast inflammation. Total RNA was extracted and sequenced to identify differentially expressed genes and enriched pathways.

first: Li

last: Zhang

first: Jie

last: Zheng

first: Meng

last: Pan

first: Xia

last: Li

first: Xiaoqing

first: Shuoting

last: Wang

first: Zirou

last: Shang

first: Han

last: Cao

first: Xiaoying

last: Chen


title: V gamma 1 gamma-delta T cells steer airway macrophages towards a pro-fibrotic response in an autochthonous lung cancer mouse model. [RNA-Seq]

first: Robin

last: Shaw

overall_design: Bulk RNA-seq was performed on FACS-isolated alveolar macrophage subsets from: 1) Tumour-bearing KM lungs from Tcrd knockout mice vs wild type to identify differentially expressed genes. These genes were used to create a module score for assessing scRNA-seq clusters. 2) Tumour-bearing KM lungs, comparing SiglecF low and SiglecF hi AMs to define transcriptional programmes associated with profibrotic versus immunoreactive states; these signatures were then related back to scRNA-seq clusters.

first: Ximena L.

last: Raffo-Iraolagoitia

first: Amanda J.

last: McFarlane

first: Sarah

last: Laing

first: Ryan

last: Corbyn

first: Lindsey W. G.

last: Arnott

first: Frédéric

last: Fercoq

first: Lynn

last: McGarry

first: Judith

last: Secklehner

first: Marco

last: De Donatis

first: John B. G.

last: Mackey

first: Bjorn

last: Kruspig

first: Robert

last: Wiesheu

first: Ya-Ching

last: Hsieh

first: Kai

last: Rakovic

first: John

last: Le Quesne

first: Graeme

last: Clark

first: Colin

last: Nixon

first: Crispin

first: Kristina

last: Kirschner

first: Calum C.

last: Bain

first: Daniel J.

last: Murphy

first: Seth B.

last: Coffelt

first: Leo M.

last: Carlin


title: Disruption of ligand binding domain of the Epidermal Growth Factor Receptor by sequential knock in CRISPR/Cas9 genome editing alters its subcellular localization and phosphorylation in cervical cancer cells

city: Chicago

first: Jelena

last: Popovic

state: IL

address: 300 E Superior St. Tarry 4-770

department: Radiation Oncology

institute: Northwestern University

summary: Upregulation of Epidermal Growth Factor Receptor is evident in most cases of cervical cancer and is usually associated with a poor prognosis. At the same time, therapies directed against EGFR are generally not successful in this type of cancer, which suggests that therapeutic inactivation of EGFR can be easily overcome. In order to evaluate mechanisms by which cervical cancers with alterations in EGFR signaling thrive, we have generated several EGFR mutant clones by CRISPR/Cas9 genome editing. This work details the approach used to generate EGFR mutant cells and describes changes in cell characteristics associated with decreased quantity and altered subcellular distribution of EGFR.

overall_design: We performed CRISPR/Cas9 experiments with the intention to introduce amino acid substitutions into EGF binding region of EGFR gene in cervical cancer cell line ME180 genome. We porformed Whole genome sequencing in order to get full insight into CRISPR/Cas9 results in 5 single cell isolated clones  The aim of this approach was to precisely evaluate the variants of EGFR across the entire EGFR gene region and to compare the entire genomes between the clones and wild type cells.

first: Anna

last: Hahut

first: Tatjana

last: Paunesku

first: Gayle

last: Woloschak


title: The COMPASS subunit Bre2 targets CRF Arp9 to regulate the bio-synthesis of secondary metabolite AFB1 and virulence in Aspergillus flavus [ATAC-seq]

city: Fuzhou

first: Sun

last: Minghui

address: Cangshan

institute: Fujian Agriculture and Forestry University

summary: Aspergillus flavus, along with its notorious secondary metabolite aflatoxin B1 (AFB1), serious endangers human health. We previous revealed that histone methyltransferase complex COMPASS plays a crucial role in regulating various biological processes of A. flavus, but underlying mechanism is unclear. Here, through genetic assay and invading experiments, we found that Bre2, key subunit of COMPASS, regulates AFB1 bio-synthesis, fungal morphogenesis and virulence to crop and animal through H3K4 methylation. ChIP-seq and biochemistry analysis revealed that chromatin remolding factor (CRF) Arp9 is directly targeted by Bre2, and Arp9 implements bio-function through interacting with CRFs: RSC8, Arp7 and Sth1. ATAC analysis revealed that Arp9 deeply participates in fungal pathogenicity through regulating a serial secondary metabolism, morphogenesis and virulence associated regulators by modulating the chromatin conformation. The study revealed an epigenetic signaling pathway from COMPASS to Arp9 mediating chromatin remolding, which provides potential strategy for prevention and control of pathogenic fungi and mycotoxins.

overall_design: To reveal the potential complex regulatory network of the Arp9, ATAC-seq analysis was carried out on the WT and ΔArp9 strains.

first: Minghui

last: Sun

first: Zhenhong

last: Zhuang


title: Bulk RNA-seq analysis of mouse bone under microgravity (0G) and normal gravity (1G)

city: Shimotsuke

first: Makoto

last: Kuro-o

state: Tochigi

address: 3311-1 Yakushiji

institute: Jichi Medical University

summary: This study presents bulk RNA-seq data generated from mouse bone samples to investigate transcriptomic changes induced by microgravity. Total RNA was extracted from bone tissues, and RNA-seq libraries were prepared using a poly(A)-selection protocol and sequenced on an Illumina platform. The resulting data were used to compare gene expression profiles between ground control (1G) and microgravity (0G) groups.

overall_design: Bulk RNA-seq was performed on bone tissues collected from mice under control and microgravity conditions. For each condition, total RNA extracted from bone tissues of six mice was pooled in equal amounts and subjected to bulk RNA-seq analysis.Differential gene expression analysis was conducted to identify transcriptional changes associated with exposure to microgravity.

first: Hirosaka

last: Hayashi

first: Yutaka

last: Miura

first: Yoshitaka

last: Iwazu

first: Hideyuki

last: Mukai

first: Yoshiyuki

last: Mori

first: Takahiro

last: Kuchimaru

first: Nobuhiko

last: Ohno

first: Tatsuya

last: Aiba

first: Risa

last: Okada

first: Daisuke

last: Kamimura

first: Dai

last: Shiba

first: Hiroshi

last: Kurosu


title: CMS subtypes correlate with complete response in trial of neoadjuvant Galunisertib plus chemoradiation in rectal cancer

city: Portland

first: venkatesh

last: rajamanickam

state: OR

address: 4805 NE Glisan St, Suite 2N35

institute: Earle A. Chiles Research Institute

summary: Improving response to neoadjuvant therapy for patients with locally advanced rectal cancer has the potential to improve organ preservation and disease-free survival. Knowing which patients may need therapeutic escalation or de-escalation from standard-of-care treatment remains an area of investigation. We previously reported the primary and secondary endpoints of our single-arm study combining transforming growth factor beta receptor inhibitor, Galunisertib, with neoadjuvant chemoradiation in patients with locally advanced rectal cancer. Here we analyze RNA sequencing data obtained from tissue biopsies at baseline and after 2 weeks of galunisertib. Differences in expression of pathways associated with MYC, inflammation, and epithelial-to-mesenchymal transition were observed between complete responders (CR) and <CR, with galunisertib upregulating MYC pathway expression in CR. Radiosensitivity and TGFβ response scores demonstrated limited ability to predict for response to galunisertib + chemoradiation. Typically treatment resistant consensus molecular subtype 4 (CMS4), characterized by TGFβ expression, was associated with response to galunisertib + chemoradiation. Differences in correlations between RNA based measures of cell composition and immunohistologic quantification of infiltrates and extracted MRI parameters were observed for CIBERSORT, MCPcounter, and Xcell methodologies. Based on these data, we hypothesize that the stromal radioresistant phenotype driven by TGFβ can be overcome by the addition of galunisertib to chemoradiation in rectal cancer.

overall_design:
RNA sequencing data obtained from tissue biopsies at baseline and after 2 weeks of galunisertib

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

first: Venkatesh

last: Rajamanickam

first: Kristina

last: Young


title: LSECs promote MASH progression via IL-1R1-mediated chemokine production induced by macrophage-derived IL-1β

status: Public on Jan 31 2026

city: Suita

first: Kenji

last: Fukumoto

state: Osaka

address: 2-2 Yamadaoka

department: Gastroenterology and Hepatology

institute: Osaka University Graduate School of Medicine

summary: In LSEC of MASH model mice, Il1r1 gene expression was elevated, and CXCL10 gene expression was upregulated compared to the normal diet group. Macrophage-derived IL-1β, whose secretion was enhanced via autophagy impairment induced by fatty acid overload, activated JNK in LSEC, leading to increased expression of CXCL10 and CCL2. The expression levels of these chemokines positively correlated with the NAFLD activity score in MASH patients. Furthermore, spatial transcriptomic analysis of liver tissue from MASH patients revealed high expression of IL1R1, CXCL10, and CCL2 in periportal LSEC, which were in close proximity to numerous macrophages.

overall_design: Western diet was used as the MASH mouse model. 6-week-old male C57BL/6J mice were fed either a normal diet (ND) (n = 2) or a Western diet (WD) (n = 1) for 12 weeks, after which they were sacrificed. The Western diet (D20092804) was custom-formulated by Research Diets, Inc. (New Brunswick, NJ, USA) to be high in fat (36.4% kcal, primarily from milk fat), cholesterol (1.21%), and sucrose-enriched carbohydrates (48.4% kcal). The mouse liver was dissociated into single cells using pronase and collagenase perfusion, followed by sample preparation for scRNA analysis.

first: Hayato

last: Hikita

first: Seiya

last: Kato

first: Yoichi

last: Sasaki

first: Yuta

last: Myojin

last: Motooka

first: Tetsuo

last: Takehara


title: Integrative epigenomic profiling of VPA treatment in HEK293 cells

city: Tokyo

first: Yutaka

last: Saito

department: Artificial Intelligence Research Center (AIRC)

institute: National Institute of Advanced Industrial Science and Technology (AIST)


title: Transcriptomes of capsule swapped-strains in Klebsiella (K1, K2, K3, K24)

first: Hugo

last: Varet

address: 28 rue du Docteur Roux

summary: We use the bacterium Klebsiella spp. as a model organism, we are interested in the bacterial capsule and the functional and evolutionnary consequences of capsule exchanges.

overall_design: We have 4 different genetic backgrounds in which we have deleted the capsular locus (∆cap: complete deletion mutant) and then separately inserted 4 different capsular loci (K1, K2, K3, and K24). We want to compare RNA expression upon capsule deletion or swap using the specific reference genome.

first: Julie

last: Le Bris

first: Eduardo

last: Rocha

first: Olaya

last: Rendueles


title: The COMPASS subunit Bre2 targets CRF Arp9 to regulate the bio-synthesis of secondary metabolite AFB1 and virulence in Aspergillus flavus

first: Sun

last: Minghui

summary: In this study, To determine the chromatin distribution pattern of Bre2-regulated H3K4me3 at the genome-wide level, we used the BRE2 knockout strain constructed in this study as a control; Chip-sequencing (ChIP-seq) experiments were performed in WT strains using an antibody to H3K4me3 to search for target genes regulated by BRE2 through H3K4me3 by bioinformatics analysis to elucidate Bre2 regulates the growth, toxin production and pathogenesis of Aspergillus flavus.

overall_design: To reveal the potential complex regulatory network of the Bre2, ChIP-seq analysis was carried out on the WT and ΔBre2 strains with H3K4me3 Antibody .

first: Minghui

last: Sun

first: Zhenhong

last: Zhuang


title: APOBEC3-mediated mutagenic processes in DNA-repair-deficient HCT116 cells selectively induced by high-dose 5FdUR treatment.

city: Budapest

first: Angela

last: Bekesi

address: Műegyetem rakpart 3.

department: Department of Applied Biotechnology and Food Science

country: Hungary

institute: Budapest University of Technology and Economics, Faculty of Chemical Technology and Biotechnology

summary: The presence of genomic uracil and its respective repair play key roles in colorectal, gastric, and other solid tumor therapies targeting thymidylate biosynthesis. Previously, we established that the treatment of HCT116 colon cancer cell lines with either raltitrexed (RTX) or 5-fluoro-2’-deoxyuridine (5FdUR), two potent inhibitors of thymidylate synthase, results in characteristic uracil patterns (PMID: 32956035). Here, we focus on drug-specific differences manifested in the drug-induced mutagenesis. Therefore, whole genome sequencing was performed in drug-treated (5FdUR or RTX) HCT116 cells that are deficient and stably express the UNG inhibitor protein, UGI. Mutational analysis revealed a significant increase in the frequency of C-to-T somatic transitions selectively upon high-dose 5FdUR treatment in DNA-repair deficient cells. The mutational spectra and the clustered nature of these transitions pointed to the action of DNA cytidine deaminases. Indeed, an induction of some APOBEC3 enzymes was experimentally confirmed upon the high-dose 5FdUR treatment, in parallel with decreased cytotoxicity, as compared to the low-dose, or any efficient doses of RTX. The observed drug-induced mutagenicity and decreased cytotoxicity might be relevant for personalized cancer therapy.

overall_design: We performed whole genome sequencing experiments from UGI expressing HCT116 cells treated with either 0.1 or 20 microM of RTX or 5FdUR for 48 hours. Samples are as follows: 5FdUR_0.1_UGI_HCT116, RTX_0.1_UGI_HCT116, 5FdUR_20_UGI_HCT116, RTX_20_UGI_HCT116, and the non-treated control: NT_UGI_HCT116). Genomic DNA was isolated from each sample and fragmented to approximately 300 bp fragments by sonication. Sequencing libraries were prepared using NEBNext Ultra II DNA Library Prep Kit for Illumina (NEB, Ipswitch, MA, USA), and were sequenced by Illumina paired-end reads (PE)150 bp in a Novaseq 6000 platform by iBioScience (Pécs, Hungary). Reads were filtered and aligned to the reference human genome (GRCh38.d1.vd1, (https://gdc.cancer.gov/about-data/data-harmonization-and-generation/gdc-reference-files)). For details, see the Supplementary Method of the related publication. Genomic variants called using mutect2 (GATK4) from treated vs. non-treated input samples in several arrangements defined in the names of each vcf file. For details, see the Supplementary Method of the related publication.

first: Eszter

last: Holub

first: Gábor

last: Papp

first: Hajnalka

last: Pálinkás

first: Milda

last: Szajkó

first: Richard

last: Izrael

first: Beáta

middle: G

last: Vértessy

first: Angéla

last: Békési


title: Transcriptomic analysis in relation to adventitious rooting of different petunia species

status: Public on Jan 30 2026

city: Erfurt

first: Sindy

last: Chamas

address: Kuehnhaeuser Strasse 101

country: Germany

institute: Erfurt Research Centre for Horticultural Crops, University of Applied Sciences Erfurt

summary: Excision-induced adventitious rooting of cuttings is a key developmental process for vegetative propagation of many crops, that involves a phytohormone-controlled reprogramming and redifferentiation of specific cells in the stem base. Even though the important role of auxin as inductor of adventitious roots is widely accepted, the endogenous control of auxin action at whole cutting level and the interaction with other hormones are not completely understood. Comparing the genome-sequenced Petunia species P. axillaris and P. inflata, we monitored the transcriptome of phytohormone-related genes in different cutting sections by a phytohormone-targeted microarray. Expression of 17 selected auxin-related genes was quantified in the same RNA samples by RT-qPCR.

sample_organism:
Petunia axillaris
Petunia integrifolia subsp. inflata

overall_design: Gene expression in five different tissues (basal leaves, upper leaves, shoot apex, upper shoot and stem base) of Petunia cuttings was measured at 0, 0.5, 2, 24 and 72 hours post excision. Three replicates were taken for each time point and tissue. Cuttings from two Petunia species (P. axillaris and P. inflata) were used for this experiment.

first: Uwe

last: Druege

first: Katharina

last: Federspiel


title: Kupffer Cell Calibration of T Cell Responses via VSIG4-CD5 Interaction Promotes Tumor Evasion[TCR-Seq]

city: Hefei

first: xia

last: zhou

address: huang shan Road 443

institute: university of science and technology of china

summary: Liver metastasis often resists T cell-based immunotherapy, indicating an adaptation of metastatic tumors towards reduced immunogenicity in the liver. Here we demonstrate that VSIG4, an immune checkpoint molecule predominantly expressed on Kupffer cells, plays an opposing role in determining the growth of liver metastases with varying antigenicity by modulating cognate TCR signaling through its interaction with CD5. Mechanistically, VSIG4-CD5 engagement impedes activation of low-affinity CD8+ T cells while enhancing responses of high-affinity CD8+ T cells by rescuing them from activation-induced cell death. This bi-directional regulation favors growth of metastatic tumor clones with low antigenicity, and fosters an T cell-unfavorable immune landscape as metastatic liver cancer progresses. Blockade of VSIG4-CD5 interaction with a newly generated anti-VSIG4 nanoantibody sensitizes liver metastases to anti-PDL1 therapy, achieving remarkably synergistic efficacy in mice. Our findings provide mechanistic insights into cancer immunoediting in liver metastasis and propose a promising approach for treating immunologically cold tumors.

overall_design: MC38 cells were injected into WT and VSIG4 ko mice. 14 days latter, CD8+ T cells from tumor-bearing WT and VSIG4 ko mice were isolated and sorted by FACS, Further RNA-seq were performed and analyzed.

first: Xia

last: Zhou

first: Wei

last: Liu

first: Jing

last: Hu

first: Qi

last: Yao


title: Multiple defects in mouse stem cell based embryo models lacking all Hox function [multiome]

city: Paris

first: Hocine

last: Rekaik

address: 11, Place Marcelin Berthelot

institute: College de France

summary: Mammals have four genomic copies of an ancestral Hox cluster, with a total of 39 genes. While gene inactivation approaches and full cluster deletions have revealed their critical functions during early development, the effect of removing all Hox function has remained elusive due to both biological and technological challenges. We have used mouse gastruloids, an ES cells-derived embryo model where Hox genes are properly activated in time and space, to assess the effect of their complete absence. We report that gastruloids lacking Hox function can still elongate and reach a general shape resembling their control counterparts, with a well-established AP polarity. However, unlike controls, they fail to produce any endoderm and are unable to properly segment their presomitic mesoderm into persistent somite-like structures. Instead, they produce a type of mesoderm with a more anterior identity. We thus propose that, in this system at least, HOX proteins are necessary to posteriorize an existing anterior ‘ground-state’ structure, in part by promoting and/or maintaining the epithelialization of cellular condensations. Multiomes analysis revealed range of modifications in chromatin accessibility in the absence of any HOX proteins, involving in particular variations in the binding of the co-factor PBX1. In contrast, neuro-mesodermal progenitor (NMP) cells are not overtly affected in mutant gastruloids, even though they normally initiate strong Hox gene transcription, suggesting that these cells are used as vehicles to translate a temporal sequence of activation into an AP colinear transcript distribution, which becomes functional at a later stage only.

overall_design: scMultiome of wt and Hox-/- gastruloids at 96h and 120h

first: Lucille

last: Lopez-Delisle

first: Alexandre

last: Mayran

first: Yuliia

last: Romaniuk

first: Cynthia

last: Diabanza

first: Anne-Catherine

last: Cossy

first: Denis

last: Duboule


title: Kupffer Cell Calibration of T Cell Responses via VSIG4-CD5 Interaction Promotes Tumor Evasion [bulkRNA]

overall_design: B16F10 cells were injected into WT and VSIG4 ko mice. 7 days latter, Kupffer cells from tumor-bearing WT and VSIG4 ko mice were isolated and sorted by FACS, Further RNA-seq were performed and analyzed.


title: Micro-bulk RNA-seq of trilaminar omphalopleure of Monodelphis domestica to investigate placental cytokine signaling

city: New Haven

first: Gunter

last: Wagner

state: CT

address: 165 Prospect Street

department: Ecology & Evolutionary Biology

institute: Yale University

summary: The brief placental attachment of the gray short-tailed opossum Monodelphis domestica spans only the final two days of the 14-day pregnancy. During this time the fetus grows rapidly and a pronounced spike in inflammatory signaling occurs. It was recently discovered that these cytokines are produced primarily by fetal cells, the syncytial knots which develop at the end stage of placentation after day 13 of gestation. To investigate this further, we conducted laser microdissection on placental membranes (omphalopleure) at 13.5 days post copulation to compare to published transcriptomes at 12.5 days post copulation. Analysis revealed indeed a pronounced expression of inflammatory cytokines in the 13.5 samples. We hypothesized that placental cytokines act as solicitation signals benefitting the fetus by effects on maternal nutrient transfer. To test this, we administered anti-inflammatory drugs to pregnant opossums during the attachment phase targeted at three arms of this response: IL1A via the receptor inhibitor anakinra, IL6 via the receptor inhibitor tocilizumab, and prostaglandin E2 via the PTGS2 synthetase inhibitor meloxicam. Inhibition of IL-1 and IL-6 signaling resulted in significant increases in fetal biomass, suggesting that they impose a cost to biomass acquisition by offspring rather than acting in direct solicitation. However, in the case of anakinra, saline-treated control individuals showed a greater mean surviving litter size compared to IL-1-inhibited animals. Together, our results suggest that marsupial end-pregnancy inflammation has acquired a novel function modulating both fetal growth and survival during pregnancy.

overall_design: Opossums were mated (no drug treatment or other intervention) and pregnant uteri were collected at 13.5 days post copulation. Placental tissues, which normally appose maternal uterine lining, were isolated by laser microdissection and subjected to RNA sequencing.

first: Daniel

last: Stadtmauer


title: Novel variants in the splicing factor gene SF3B1 are associated with neurodevelopmental disorders

city: BREST

first: Delphine

last: Bernard

address: 22 avenue Camille Desmoulins

institute: UMR1078 - Université de Bretagne Occidentale

summary: SF3B1 is an essential and ubiquitous splicing factor that plays a pivotal role in the early steps of pre-mRNA splicing. Recurrent somatic missense mutations in SF3B1 are frequent in cancers, but no constitutional variant has been reported so far. We describe here a cohort of 26 individuals with neurodevelopmental disorders, harbouring SF3B1 constitutional heterozygous variants that appeared mostly de novo. Patients present with a global developmental delay, associated with variable neurological and facial dysmorphic traits. A dichotomy may emerge between patients harbouring predicted loss of function (n=9) and missense variants (n=17), the latter being associated with a more severe and syndromic phenotype, including heart and gastrointestinal anomalies. We focused on de novo SF3B1 missense variants, which were largely distinct from those reported in cancer. Functional complementation assays show that de novo SF3B1 missense variants did not cause a loss of function of the protein. Targeted and genome-wide analysis of RNA splicing reveal that they affect canonical and alternative splicing more moderately than somatic variants, and subtly modify the splicing of many transcripts, some of which are involved in neurodevelopmental disorders. SF3B1 joins the short list of U2 snRNP components involved in both cancer and neurodevelopmental disorders.

overall_design: RNA-seq profiling of K562 cells stably expressing wild type or variant SF3B1 (K700E, E722K, P780L, N829S) upon induction with 2 microg/mL of doxycycline for 7 days (in RPMI, 10% FBS, 2mM Gln). Biological independent replicates (n=3) were realised for each condition. RNA sequencing was performed by Novogene on an Illumina NovaSeq platform, using a 150-bp paired-end sequencing strategy.

first: Kevin

last: Uguen

first: Tiffany

last: Bergot

first: Solène

last: Chapalain

first: Marie-Pier

last: Scott-Boyer


title: Trans-regulation of heterochromatin underlies genetic variation in 3D genome contacts III

city: Bar Harbor

first: Christopher

middle: Lee

last: Baker

address: 600 Main Street

department: Research

institute: The Jackson Laboratory

summary: Background Genetic variation drives phenotypic diversity and disease susceptibility. Trans-acting genetic variation coordinates genome-wide chromatin changes, yet the molecular mechanisms underlying this regulation remain largely unknown. Here, we use the power of mouse genetics to investigate how genetic variation at trans-acting loci regulates 3D chromatin interactions. Results Genetically variable 3D interactions were identified using HiChIP to map H3K27ac-associated regulatory elements in C57BL/6J (B6) and DBA/2J (D2) embryonic stem cells (ESCs). We identified 4,962 strain-differential interactions (~5% of total interactions), 71% of which overlapped chromatin accessibility quantitative trait loci (caQTL), establishing that chromatin interaction variation is predominantly heritable. These differential interactions showed coordinated changes in chromatin state and gene expression, with stronger interactions associated with increased accessibility and transcription. Notably, loci regulated in trans exhibited a unique chromatin signature where weaker interactions were enriched for H3K9me3-marked heterochromatin. This pattern was 20-fold more enriched at trans-regulated targets compared to cis, implicating heterochromatin in trans-regulation of 3D genome structure. Analysis of F1 hybrids revealed dominant repressive effects, consistent with heterochromatin-mediated trans-regulation. To causally test this mechanism, we generated reciprocal congenic mouse strains carrying a Chr13 trans-QTL region on otherwise inbred genetic backgrounds. Integrated multiomic profiling of congenic ESC lines demonstrated that this single locus coordinates changes in H3K9me3, H3K27ac, chromatin accessibility, and 3D contact frequency at hundreds of distal genomic regions. Remarkably, 73-83% of differential interactions at Chr13 trans-QTL targets changed in the predicted direction, demonstrating that heterochromatin-mediated trans-regulation coordinately regulates hundreds of regulatory loci. Conclusions This work establishes heterochromatin formation as a mechanism by which genetic variation at trans-acting loci coordinates changes across chromatin accessibility, histone modifications, and 3D genome organization, providing a framework for understanding how early developmental chromatin states could generate phenotypic variation while preserving essential developmental programs.

overall_design:
H3K27ac Dovetail MNase HiChIP in C57BL/6J and DBA/2J, B6.D2-(rs30079041-rs51756099)/Bakr (QJ), and D2.B6-(rs29224292-rs51756099)/Bakr (XE) mouse embryonic stem cells (2 technical replicates each).

** QJ and XE are congenic strain designations used internally within the lab. For clarity and consistency with standardized nomenclature, QJ samples are referred to as B6-13D2 and XE samples as D2-13B6 throughout the manuscript.


title: Trans-regulation of heterochromatin underlies genetic variation in 3D genome contacts IV

overall_design:
ChIP-seq of the histone modification H3K27ac and H3K9me3 in C57BL/6J and DBA/2J, B6.D2-(rs30079041-rs51756099)/Bakr (QJ), and D2.B6-(rs29224292-rs51756099)/Bakr (XE) mouse embryonic stem cells (2 or 3 biological/technical replicates each).

** QJ and XE are congenic strain designations used internally within the lab. For clarity and consistency with standardized nomenclature, QJ samples are referred to as B6-13D2 and XE samples as D2-13B6 throughout the manuscript.


title: Transcriptome analysis of VapC36 overexpression in Mycobacterium tuberculosis

city: Bangalore

first: Munmun

last: Bhasin

state: Karnataka

address: CV Raman Rd

department: Molecular Biophysics Unit

country: India

institute: Indian Institute of Science

summary: Using Total RNA sequencing, We report the effects of VapC36 overexpression on the transcriptome of M. tuberculosis. For RNA-seq experiments, early-log phase cultures (OD600nm ~ 0.2-0.3) of M. tuberculosis strains harboring either pTetR or pTetR-vapC36  were induced with the addition of 50 ng/ml Atc for 24 h. For total RNA isolation, induced cultures were harvested by centrifugation, washed twice with 1x PBS and lysed by bead beating in Trizol. Total RNA was extracted by phenol-chloroform, precipitated with isopropanol and eluted using Qiagen RNA isolation kit as per manufacturer’s instructions. We report that VapC36 resulted in increased transcripts levels of proteins encoding for ribosomal proteins  and copper responsive proteins of M. tuberculosis.

overall_design: Cells harbouring pTetR (Vector only) or pTetR VapC36 were used for RNA-Seq analysis. Experiments were performed thrice for each strain.

first: Arun

last: Sharma

first: Gopinath

last: Chattopadhyay

first: Manisha

last: Singh

first: Prabhakar

last: Babele

first: Raghavan

last: Vardarajan

first: Ramandeep


title: snRNA-sequencing of two human dorsal root ganglia

city: DURHAM

first: Jing

last: Xu

state: NC

address: 816 Louise Circle

institute: Duke university

summary: The dorsal root ganglion (DRG) integrates peripheral sensory signals and plays a central role in pain and neuropathy. Using single-nucleus RNA sequencing (snRNA-seq) of human DRG. We spearted 17 clusters and identified 6 major cell types, including sensory neurons and satellite glial cells (SGCs).

overall_design: We performed single-nucleus RNA sequencing (snRNA-seq) on 2 human DRG tissue

first: Charles

last: Novak

first: Zihan

last: Yan

first: Dmitry

last: Velmeshev

first: Richard

middle: E

last: Cheney

first: Ru-Rong

last: Ji