title: Ribonuclease 5 suppresses intestinal tumorigenesis

city: HangZhou

first: xin

last: xu

state: Zhejiang

address: No. 866, Tang Road, Yuhang District, Zhejiang University, Zijingang Campus, School of Medicine.

institute: Zhejiang university

type: Non-coding RNA profiling by high throughput sequencing

summary: Understanding on the transformation of normal intestinal tissue to tumor remains incompleted. Ribonuclease 5 (RNase5) was traditionally recognized as a tumor promoter, here we found it exhibited a dose-dependent tumor-inhibitory effect in normal intestine. Functionally, RNase5 controlled crypt stem and transit amplifying cell proliferation rates to maintain homeostasis, thus suppressing tumor initiation. Mechanistically, cytoplasmic RNase5 restricted protein synthesis to an appropriate level by producing tRNA-derived stress-induced tRNA fragments (tiRNAs) to accommodate intestinal steady state. RNase5 supplementation reduced adenomas if administered during tumorigenesis onset but enhanced tumor growth if added during progression stage. Furthermore, our nested case‒control study revealed that low serum ANG predicted higher CRC risk. Our finding suggests that RNase5 plays dichotomous roles in intestinal tumor initiation and development, and its serum level may serve as a biomarker for CRC risk predication; its supplementation might be an intervention measure for the population with extremely low serum RNase5.

overall_design: To investigate the function of Ribonuclease 5 in intestinal crypt homeostasis, we isolated crypts of WT and RNase5 konckout (KO) mice and performed gene expression profiling analysis using data obtained from RNA-seq,  Ribo-seq and small RNA-seq.

first: Xiaoliang

last: Shi

first: Rongpan

last: Bai

first: Jingzhou

last: Chen

first: Hao

first: Yaxin

last: Liu

first: Zhengrong

last: Yao

first: Muxiong

first: Jun

last: Sun

first: Xin

last: Xu

first: Ning

last: Shen

first: Yuanhui

last: Mao

first: Guo-fu

last: Hu

first: Mingjuan

last: Jin

first: Kun

first: Jinghao

last: Sheng

first: Zhengping


title: Lysosomal control of type I interferon induction via Ragulator-Rag complex [ATAC-seq]

status: Public on Dec 31 2025

city: Guangzhou

first: Chun-Yan

last: Lim

state: Guangdong

address: No. 9 XingDaoHuanBei Road, Guangzhou International Bio Island

country: China

institute: Guangzhou National Laboratory

type: Genome binding/occupancy profiling by high throughput sequencing

summary: The type I interferon (IFN) response is a pivotal transcription program in the host innate immunity against infectious viruses that induces a multitude of interferon-stimulated genes (ISGs) to antagonize every stage of viral replication. Aberrant IFN response often leads to enhanced viral susceptibility or autoimmune conditions. Accordingly, type I IFN induction is tightly regulated from viral recognition to signaling propagation and transcriptional activation to cytokine production. Lysosomes, which are essential organelles for cellular homeostasis and metabolic signaling, play an evolutionarily conserved role in viral clearance. Through their degradative capacity and recycling function, lysosomes facilitate the containment and destruction of viral particles or debris delivered via endocytic, autophagic, and phagocytic routes. Despite the central role of lysosomes in virus-host interactions, it remains unclear whether type I IFN induction requires direct lysosomal input. Here, we identified the lysosomal scaffold Ragulator as crucial for IFN-β transcriptional activation through an antiviral screen using a GFP-expressing Influenza A virus as a readout. Independent of their known roles in mTORC1 regulation, the Ragulator-dependent antiviral response requires downstream heterodimeric Rag GTPases that alter their nucleotide-loading states to establish the IFN-I gene signature. Depleting Ragulator or Rag GTPases causes exhaustion of a regulatory pool of interferon-regulator factors (IRFs), leading to abrogated Ifnb1 transcription, IFN-β secretion, and ISG response, thereby enhancing susceptibility to viral infections both in cells and in vivo. Thus, our findings reveal a new role for lysosomes in the nuclear transcription of antiviral innate immunity.

overall_design: Three biological replicates were analyzed for each of 2 conditions (two genotypes; 2 treatments per genotype)

first: Miao

last: Lei

first: Wenxiang

first: Zeming

last: Feng

first: Lulu

last: Wang


title: Hemolysis-induced hepatic ferroptosis following xenotransfusion of genetically modified pig red blood cells

status: Public on Dec 30 2025

city: Jeongeup-Si

first: Ju Young

last: Lee

address: 30 Baekhak 1 Gil,

country: South Korea

institute: Korea institute of toxicology

type: Expression profiling by high throughput sequencing

summary: Following a worsening blood supply shortage, researchers are investigating the application of genetically modified pig blood for human transfusion. To overcome cross-species immunological barriers, researchers utilize gene editing to remove the expression of three major carbohydrate xenoantigens (α-Gal, Neu5Gc, and Sd(a)) and insert genes, such as human protective genes (hCD55 and hCD39). This study aimed to investigate the mechanisms underlying long-term hepatic injury following xenotransfusion of genetically modified pig red blood cells (pRBCs). We xenotransfused pRBCs genetically engineered with GGTA1-/-(α-Gal -); CMAH-/-(Neu5Gc-); β4GALNT2-/-(Sd(a) -); hCD55; hCD39 into a non-human primate (NHP) model of acute hemorrhage hemolysis and evaluated the long-term immune response to xenogeneic RBCs in the liver, a key organ for RBC metabolism. Immediately after xenotransfusion (D+1), significant elevations of liver enzymes (AST, ALT) and iron-related factors were observed in the serum levels of the recipients, which were normalized by D+21. However, long-term analysis revealed excessive accumulation of iron ions in the liver and decreased expression of antioxidant enzymes. The resulting endoplasmic reticulum stress (increased GRP78/BiP expression), lipid peroxide accumulation, and iron-dependent cell death (ferroptosis) persisted in the liver of the recipient. These results suggest that gene editing alone cannot completely block oxidative stress damage caused by impaired RBC lysis. Notably, transcriptomic and immunohistochemical analyses in the NHP model identified the direct role of ferroptosis in xenotransfusion-induced liver injury. Therefore, we propose that a multilayered approach, including blocking the ROS-Iron axis and administering ferroptosis inhibitors, is needed to ensure long-term safety in the clinical development of xenotransfusion.

overall_design: To investigate DEG profiles of liver of Triple-gene KO pig RBC transfused-NHPs

first: Ha-Young

last: Shin

first: Young-Jin

last: Jang

first: Hyung-Sun

last: Kim

first: Seon-Ryoung

last: Park

first: Goo-Hwa

last: Kang

first: Joohyun

last: Shim

first: Nayoung

last: Ko

first: Jeong Ho

last: Hwang


title: Phase 1 study of chidamide in combination with venetoclax, azacitidine, aclarubicin, cytarabine and G-CSF for refractory/relapsed acute myeloid leukemia: Clinical safety, efficacy and correlative analysis

city: Beijing

first: Yanan

last: Wen

state: Beijing

address: Fuxing Street 28th, Haidian District, Beijing, China

institute: Chinese PLA General Hospital

summary: For scRNA-seq analysis, bone marrow mononuclear cells (BMMCs) from four consecutively enrolled patients (July–September 2023) were processed using the 10x Genomics platform. Patients selected for scRNA-seq analysis were consecutively enrolled during the study period to minimize selection bias. Their diverse clinical outcomes provide a valuable spectrum for correlating transcriptomic changes with treatment efficacy.

overall_design: BM cells from patients with AML were collected in EDTA tubes and diluted 2:1 in ice-cold FACS buffer. Mononuclear cell separation was accomplished using density centrifugation media (Ficoll-Paque; GE Healthcare Life Sciences) at a 1:1 ratio with BM cells. Subsequently, the cell suspension, with a concentration ranging from 700 to 1,200 cells/µl and a cell viability exceeding 85%, was loaded onto the Chromium Single Cell Controller (10× Genomics) to generate single-cell gel beads in the emulsion, following the manufacturer’s protocol and employing the Chromium Single Cell 3' Library and Gel Bead Kit V3.1 (10× Genomics, PN1000268). The libraries were sequenced on an Illumina NovaSeq 6,000 sequencer.


title: Expression of the CXCR4 S338X variant improves anti-leukemia efficacy of anti-CD19 CAR-T cells

status: Public on Dec 28 2025

city: Changchun

first: Yushu

last: Mao

address: Xinzhu Road

institute: Jinlin university

summary: Chimeric antigen receptor T (CAR-T) cell therapy has demonstrated remarkable success in treating hematological malignancies; however, antigen-positive relapse remains a significant obstacle to achieving sustained remission in B-cell acute lymphoblastic leukemia (B-ALL). To enhance the therapeutic efficacy of anti-CD19 CAR (CAR19)-T cells, we overexpressed CXCR4 in CAR19-T cells to improve their trafficking to bone marrow (BM), a key sanctuary for minimal residual disease. We engineered CAR19-T cells with overexpression of wild-type CXCR4 (CAR19/CXCR4WT-T) or gain-of-function CXCR4 S338X mutant (CAR19/CXCR4S338X-T). Both CAR19/CXCR4WT-T and CAR19/CXCR4S338X-T cells exhibited enhanced CXCR4 surface expression in vitro and in vivo compared to control CAR19-T cells, with the latter showing significantly superior improvements under all tested conditions, including engagement with CAR-specific antigens or CXCR4 ligand CXCL12. Upon engagement with CXCL12, CAR19/CXCR4S338X-T cells, but not CAR19/CXCR4WT-T cells, displayed significantly increased activation of ERK1/2 and AKT signaling pathways, as well as elevated transcription of TNF-α, IFN-γ, granzyme B, CDK6, and BCL2A1, along with strengthened effector functions, chemotaxis, and activation of anti-apoptotic pathways. Furthermore, CAR19/CXCR4S338X-T cells demonstrated significantly improved migration to and retention in the BM accompanied by increased CD45RA+CCR7+ memory T cell populations, which correlated with enhanced anti-leukemic effects following injection into B-ALL-bearing mice. This study offers a potentially effective strategy to improve the functionality and durability of CAR-T cell responses in hematological malignancies.

overall_design: RNA-seq was performed on CAR19-T, CAR19/CXCR4WT-T, and CAR19/CXCR4S338X-T cells treated with or without CXCL12 for 6 hours to assess alterations in CXCR4 signaling (3 individuals per group). Furthermore, focused RNA-seq analysis was carried out to investigate the enhanced CXCL12/CXCR4 signaling axis in CAR19/CXCR4S338X-T cells (3 individuals per group).

first: Zheng

last: Hu

first: Yong-guang

last: Yang


title: Blood-borne sphingosine 1-phosphate maintains vascular resistance and cardiac function.

status: Public on Dec 24 2025

city: PARIS

first: Ilaria

last: Del Gaudio

address: 56 Rue Leblanc

country: France

institute: Paris Cardiovascular research center_ InsermU970

summary: Sphingosine 1-phosphate (S1P) circulates in plasma bound to high-density lipoproteins (HDL) and albumin. In mice, isolated deficiency in HDL-S1P and endothelial cell S1P receptor (R)-1 both trigger hypertension, supporting an essential role for HDL-S1P in endothelial function. Physiological roles of albumin-S1P and myocyte S1PRs in the cardiovascular system remain incompletely defined. We report that depletion of all circulating S1P pools induces hypotension and lack of blood pressure increase with age, which contrasts with HDL-S1P deficiency and suggests an essential role for albumin-S1P in cardiovascular homeostasis. Left ventricular contractile function was also reduced but cardiac output preserved in a basal state. Cardiac function and blood pressure was partially or fully normalized by bone marrow transplantation or transfusion of erythrocytes capable of S1P production. Hypotension was accompanied by reduced peripheral resistance, and BSA-S1P, but not S1P complexed to an HDL-like chaperone, dose-dependently increased vascular resistance in isolated perfused kidneys via S1PR2 and S1PR3. Epistatic analysis supported a critical role for S1PR3 in S1P-dependent blood pressure regulation and pointed to a distinct origin of the cardiac phenotype. These observations suggests that albumin-S1P crosses the endothelium in resistance arteries to access contractile receptors, and that myocyte S1PR signaling is essential for vascular resistance and blood pressure maintenance in mice.

overall_design: RNA-seq profiling of hearts from plasma S1Pless (Sphk1f/-:2f/-:Mx1Cre+)  and littermate control male mice

first: Eric

last: Camerer


title: Decoding the Effects of Bexarotene treatment on brain of AD-like model mice: A Single-Cell Transcriptomic and Chromatin Accessibility Analysis [scRNA-seq]

city: Pittsburgh

first: Iliya

last: Lefterov

state: PA

address: 130 De Soto St

department: Environmental and Occupational Health

country: USA

institute: University of Pittsburgh

summary: Ligand activation of nuclear receptor has been linked with therapeutic implications in Alzheimer's Disease. In this study, we used AD mouse model treated with Bexarotene, an RXR agonist and performed scRNA-seq and snATAC-seq using the brain tissue. We reavealed changes in chromatin architure in brain of AD-lie mouse model in response to RXR ligand and  link those changes to the initiation of transcriptional programs at a single-cell resolution.

overall_design: We used an AD mouse model treated with Bexarotene, an RXR agonist. scRNA-seq and snATAC-seq were performed using mouse brain 10-day post-treatment to assess brain transcriptome and chromatin accessibility change in response to RXR activation.


title: Fn14 is an activity-dependent, Bmal1-regulated cytokine receptor that induces rod-like microglia and restricts neuronal activity in vivo

city: Cold Spring Harbor

first: Lucas

last: Cheadle

address: 1 Bungtown Road

institute: Cold Spring Harbor Lab

summary: To survive, organisms must adapt to a staggering diversity of environmental signals, ranging from sensory information to pathogenic infection, across the lifespan. At the same time, organisms intrinsically generate biological oscillations, such as circadian rhythms, without input from the environment. While the nervous system is well-suited to integrate extrinsic and intrinsic cues, how the brain balances these influences to shape biological function system-wide is not well understood at the molecular level. Here, we demonstrate that the cytokine receptor Fn14, previously identified as a mediator of sensory experience-dependent synaptic refinement during brain development, regulates neuronal activity and function in adult mice in a time-of-day-dependent manner. We show that a subset of excitatory pyramidal (PYR) neurons in the CA1 subregion of the hippocampus increase Fn14 expression when neuronal activity is heightened. Once expressed, Fn14 constrains the activity of these same PYR neurons, suggesting that Fn14 operates as a molecular brake on neuronal activity. Strikingly, differences in PYR neuron activity between mice lacking or expressing Fn14 were most robust at daily transitions between light and dark, and genetic ablation of Fn14 caused aberrations in circadian rhythms, sleep-wake states, and sensory-cued and spatial memory. At the cellular level, microglia contacted fewer, but larger, excitatory synapses in CA1 in the absence of Fn14, suggesting that these brain-resident immune cells may dampen neuronal activity by modifying synaptic inputs onto PYR neurons. Finally, mice lacking Fn14 exhibited heightened susceptibility to chemically induced seizures, implicating Fn14 in disorders characterized by hyperexcitation, such as epilepsy. Altogether, these findings reveal that cytokine receptors that mediates inflammation in the periphery, such as Fn14, can also play major roles in healthy neurological function in the adult brain downstream of both extrinsic and intrinsic cues.

overall_design: Hippocampal tissue from adult C57BL/6 mice was dissected, and nuclei were isolated by mechanical dissociation and lysis. Single nuclei were processed using the 10x Genomics Chromium platform with the Chromium Single Cell 3' Library and Gel Bead Kit v4 (polyA priming) according to the manufacturers instructions to generate snRNA-seq libraries. Libraries were sequenced on an Illumina HiSeq 2000 instrument with paired-end reads.

first: Austin

last: Ferro

first: Dominic

middle: J

last: Vita

first: Trevor

last: Fallon

first: Anosha

last: Arshad

first: Leah

last: Boyd

first: Tess

last: Stanley

first: Qianyu

last: Lin

first: Adrian

last: Berisha

first: Uma

last: Vrudhula

middle: M

last: Gomez

first: Irene

last: Sanchez-Martin

first: Jeremy

middle: C

last: Borniger


title: Lysosomal control of type I interferon induction via Ragulator-Rag complex [RNA-seq]

first: Chun-Yan

last: Lim

overall_design: Three biological replicates were analyzed for each of 6 conditions (two genotypes; 6 treatments per genotype)

first: Zeming

last: Feng

first: Lulu

last: Wang


title: Essential role of NONO-HOXA1-Wnt axis in cardiomyocyte differentiation [ChIP-seq]

status: Public on Dec 21 2025

city: Shanghai

first: Feizhen

last: Wu

state: Shanghai

address: Zhangheng Road 825, Pudong

department: Intelligent Medicine Institute

institute: Fudan Univ, Shanghai, China

summary: NONO is recognized as a critical molecular scaffold involved in both transcriptional and posttranscriptional regulation. Mutations in NONO are frequently linked to congenital heart diseases (CHDs) in humans. However, the mechanisms by which NONO regulates cardiac development remain elusive. Here, we identified NONO as a pivotal dual-function regulator of cardiomyocyte differentiation in human induced pluripotent stem cells (hiPSCs). NONO deficiency in hiPSCs results in a distinct defect in early cardiomyocyte differentiation. Mechanistically, NONO interacts with HOXA1 and regulates the dynamic expression of key genes during early cardiomyocyte differentiation. ChIP-seq analysis reveals that NONO loss reduces HOXA1 occupancy at target genes, compromising its transcriptional regulation. Additionally, NONO and HOXA1 cooperatively activate the Wnt signaling. Taken together, these findings establish the NONO-HOXA1-Wnt axis as a key molecular mechanism in cardiomyocyte differentiation and provid insights into the etiology of CHDs associated with NONO mutations.

overall_design:
We performed ChIP-seq of NONO in Day2-differentiated cells. We performed ChIP-seq of HOXA1 in WT and NONO-KO Day2-differentiated cells overexpressing Dox-induced HOXA1-HA using anti-HA tag antibody, Input of ChIP-seq in Day2-differentiated cells, mRNA-seq of WT,  NONO-KO Day2, 5, 7, 9-differentiated cells and HOXA1-KO Day2-differentiated cells.
We performed reChIP-seq of NONO in Day2-differentiated cells overexpressing Dox-induced HOXA1-HA using anti-HA for primary ChIP and anti-NONO for re-ChIP. We performed ChIP-seq of HOXA1 in WT and NONO-KO Day2-differentiated cells using anti-H3K27AC antibody, Input of ChIP-seq in Day2-differentiated cells. We performed ATAC-seq in Day2-differentiated cells.

first: Wei

last: Sheng

first: Guoying

last: Huang

first: Zhiyu

first: Yuan

last: Gao


title: TrAEL-seq captures DNA replication

status: Public on Dec 22 2025

city: Cambridge

first: Laura

last: Biggins

address: Babraham Research Campus

department: Bioinformatics

country: United Kingdom

institute: The Babraham Institute

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

sample_organism:
Homo sapiens
Mus musculus

platform_organism:
Homo sapiens
Mus musculus

overall_design: Refer to individual Series


title: Deep targeted sequencing reveals genomic differences between primary and recurrent high-grade serous ovarian cancer

status: Public on Dec 23 2025

city: Incheon

first: Mi-Ryung

last: Han

address: 265, Harmony-ro, Yeonsu-gu, Incheon, Republic of Korea

institute: Incheon National University

summary: High-grade ovarian cancer (HGSOC) is a highly fatal disease with frequent recurrence and high mortality rates, despite ongoing treatment advancements. Next-generation sequencing (NGS) is an experimental technique that can identify extensive genetic information, making it a key component of precision medicine. We conducted a study based on a sample of 108 patients retrospectively selected from Severance Hospital and Gangnam Severance Hospital. We aimed to identify genetic factors associated with HGSOC recurrence and survival using deep targeted sequencing. This study identified key genetic alterations associated with recurrence and survival in HGSOC and confirmed that somatic mutations are linked to disease prognosis. We expect that these findings will contribute to more precise prognosis prediction and the development of personalized therapeutic strategies for patients with recurrent ovarian cancer.

overall_design: Gene fusion profiling of primary and recurrent HGSOC patients by TSO500 targeted-sequencing. All sample was derived from tumor tissue.

first: Jae-Hoon

last: Kim

first: Seong-Woo

last: Park

first: Young-Hoon

first: Jee-Whan

first: Yoo-Kyung

last: Lee

first: Han-Byoul

last: Cho

first: In-Ho


title: Targeting mTORC2-Dependent AKT/FOXO1/RNF125 Signaling Exploits a Therapeutic Vulnerability in c-MET-Activated and β-catenin-Mutated Hepatocellular Carcinoma [SNU449]

status: Public on Dec 27 2025

city: Honolulu

first: Xue

state: HI

address: 701 Ilalo Street

department: Cancer Biology Program

institute: University of Hawaii Cancer Center

summary: Background and Aims: Approximately 10% of human hepatocellular carcinomas (HCC) exhibit concurrent c-MET activation and β-catenin gain-of-function mutations, representing a clinically relevant HCC subtype. This study aimed to investigate the role of mTORC2/AKT signaling in this subtype and identify potential therapeutic targets. Approach and Results: The mTORC2/AKT cascade was activated in c-Met/β-cateninΔ90 HCC lesions. Genetic ablation of Rictor, the essential mTORC2 subunit, strongly suppressed c-Met/β-cateninΔ90-dependent hepatocarcinogenesis. Mechanistically, both the TSC2/mTORC1 axis and FOXO1 transcription factors functioned as critical downstream effectors of mTORC2/AKT in this model. We further identified RNF125 as a direct transcriptional target of FOXO1. RNF125 overexpression significantly inhibited tumorigenesis in the c-Met/β-cateninΔ90 model and suppressed liver cancer cell growth in vitro. Notably, using an in vivo doxycycline-inducible system, we found that inducing RNF125 expression in established c-Met/β-cateninΔ90 HCC suppressed tumor progression, suggesting that activation of RNF125 may have translational implications for HCC treatment. Conclusions: Our study, for the first time, established the mTORC2/AKT/FOXO1/RNF125 axis as a critical driver and therapeutic vulnerability in c-MET-activated/β-catenin-mutated HCC. Our study filled a critical gap by defining the tumor-suppressive role of FOXO1 specifically in this HCC subtype. Furthermore, our results positioned RNF125 as a promising therapeutic target for this aggressive HCC subtype.

overall_design: RNA-seq profiling was performed on pInducer20-FOXO1AAA SNU449 cells treated with or without 2 μM doxycycline hydrochloride (Dox) for 48 hours. The experiment aimed to assess gene expression changes upon FOXO1AAA induction.

first: Xin

last: Chen


title: RNA-seq of ISL1 overexpression during islet differentiation.

city: New York City

last: Hu

state: NY

address: 430 East 67th Street

department: Developmental biology

institute: Sloan Kettering Institute

summary: This study aims to investigate the impact of ISL1 overexpression on hPSC-derived islet differentiation. hPSCs from four genotypes (WT, ISL1-/-, PDX1-/-, and PAX6-/-) were differentiated to pancreatic progenitors (day 11), transduced with ISL1-IRES2-BFP or BFP control lentivirus, and further differentiated to SC-islet (day 18). The BFP+ cells were isolated by flow cytometry sorting and subjected to RNA-seq to assess transcriptional responses to ISL1 overexpression across different genetic backgrounds.

overall_design: This study generated RNA-seq on 21 samples.  Cells were transduced with either ISL1-IRES2-BFP or BFP control on day 11 of islet differentiation and harvested on day 18. Most conditions were represented by three biological replicates. Three conditions, ISL1 overexpression in WT, BFP control overexpression in WT, and ISL1 overexpression in PDX1-/-, were represented by two biological replicates.

first: Danwei

last: Huangfu

first: Dingyu

last: Liu

first: Jiahui

last: Zhao


title: Transcriptional Profiling of Zebra Finch Hypothalamus After Chronic Heat Call Exposure

city: Clemson

first: Prakrit

last: Subba

state: SC

address: 132 Long Hall, 230 Parkway Drive

department: Biological Sciences

institute: Clemson University

summary: Late-stage zebra finch embryos were exposed to chronic playback of parental heat calls or control sounds to test how acoustic cues of extreme heat reshape hypothalamic gene expression. RNA-seq of medial hypothalamic punches revealed modest changes in neuroendocrine genes but strong downregulation of muscle and cytoskeletal programs, with evidence of altered isoform usage and enrichment in neurovascular cell populations. These findings indicate that parental heat calls drive a non-neuroendocrine transcriptional program underlying early-life developmental plasticity and acoustic-mediated adaptation to environmental extremes in birds.

overall_design: Embryonic zebra finch (Taeniopygia guttata) eggs from breeding pairs were incubated at 37.5°C and, on embryonic day 10 (E10) in the morning, were randomly allocated to either heat-call playback (whine + heat calls; n=10) or control-call playback (whine + tet calls; n=9) using a within-clutch design that balanced laying order. Playbacks were delivered via speakers attached to incubators from E10-E13 for 9 h/day over 4 days, with eggs and playbacks swapped daily between incubators to minimize incubator-specific effects. On the night of E13, all embryos were transferred to a new incubator without playback so both groups experienced identical conditions immediately prior to sampling and the experimenter could be blind to treatment. On E14 (10:00-12:00), embryos were removed from the egg and decapitated, and one 1 mm medial hypothalamic punch was collected from 100 um coronal cryosections at the level where the third ventricle first became visible; punches were frozen on dry ice and stored at -80°C. RNA was sequenced on an Illumina NextSeq 500 (75 bp, paired-end) following adapter/quality trimming (Trimmomatic v0.39), and expression was analyzed to test effects of playback condition (and sex, where applicable), with downstream co-expression network, pathway enrichment, and cell-type deconvolution analyses to link transcriptional changes to hypothalamic cell populations.

first: Katerina

last: Palios

first: Michael G.

last: Emmerson

first: Elisabetta

last: Versace

first: Katherine L.

last: Buchanan

first: Mylene M.

last: Mariette

first: David F.

last: Clayton

first: Julia M.

last: George


title: Microglia replacement by ER-Hoxb8 conditionally immortalized macrophages provides insight into Aicardi-Goutières Syndrome neuropathology

status: Public on Dec 18 2025

city: Philadelphia

first: Frederick

middle: Chris

last: Bennett

address: 3501 Civic Center Blvd

department: Neurology

institute: University of Pennsylvania

summary: Microglia, the brain’s resident macrophages, can be reconstituted by surrogate cells - a process termed “microglia replacement.” To expand the microglia replacement toolkit, we here introduce estrogen-regulated (ER) homeobox B8 (Hoxb8) conditionally immortalized macrophages, a cell model for generation of immune cells from murine bone marrow, as a versatile model for microglia replacement. We find that ER-Hoxb8 macrophages are highly comparable to primary bone marrow-derived (BMD) macrophages in vitro, and, when transplanted into a microglia-free brain, engraft the parenchyma and differentiate into microglia-like cells. Furthermore, ER-Hoxb8 progenitors are readily transducible by virus and easily stored as stable, genetically manipulated cell lines. As a demonstration of this system’s power for studying the effects of disease mutations on microglia in vivo, we created stable, Adar1-mutated ER-Hoxb8 lines using CRISPR-Cas9 to study the intrinsic contribution of macrophages to Aicardi-Goutières Syndrome (AGS), an inherited interferonopathy that primarily affects the brain and immune system. We find that Adar1 knockout elicited interferon secretion and impaired macrophage production in vitro, while preventing brain macrophage engraftment in vivo - phenotypes that can be rescued with concurrent mutation of Ifih1 (MDA5) in vitro, but not in vivo. Lastly, we extended these findings by generating ER-Hoxb8 progenitors from mice harboring a patient-specific Adar1 mutation (D1113H). We demonstrated the ability of microglia-specific D1113H mutation to drive interferon production in vivo, suggesting microglia drive AGS neuropathology. In sum, we introduce the ER-Hoxb8 approach to model microglia replacement and use it to clarify macrophage contributions to AGS.

overall_design: Myeloid cells (progenitors, monocytes, or macrophages) sequenced in vitro or in vivo (brain-engrafted), with or without CRISPR-editting. A minimum of 3 replicates per sample.

first: Nemec

last: Kelsey M

first: Uy

last: Genevieve

first: Chaluvadi

last: V Sai

first: Purnell

last: Freddy S

first: Elfayoumi

last: Bilal

first: Byerly

last: Leila

first: O'Reilly

last: Micaela L

first: O'Brien

last: Carleigh A

first: Aisenberg

last: William H

first: Lombroso

last: Sonia I

first: Guo

last: Xinfeng

first: Blank

last: Niklas

first: Oon

last: Chet Huan

first: Yaqoob

last: Fazeela

first: Temsamrit

last: Brian

first: Rawat

last: Priyanka

first: Thaiss

last: Christoph A

first: Bailis

last: Will

first: Williamson

last: Adam P

first: Wang

last: Qingde

first: Bennett

last: Mariko L

last: F Chris


title: Peromyscus maniculatus DNAm Data

city: Los Angeles

first: Steve

last: Horvath

state: CA

address: 695 Charles E. Young Drive South, Box 708822

department: Human Genetics

institute: University of California, Los Angeles

type: Methylation profiling by genome tiling array

summary: Kinship relationships between parents affect offspring fitness. Beyond its effects in heterozygosity or its impact in deleterious alleles that can be reduced to homozygosity and decrease the individuals’ fitness, the consequences of parental relatedness in the offspring remain understudied. By leveraging the availability of detailed pedigrees of captive Peromyscus we explored how parental relatedness impacts the methylome and the epigenetic age estimation of the offspring. Global CpG methylation analysis showed that parental relatedness positively impacts lifespan expectancy and reduces epigenetic aging, contributing about 13% of variation in epigenetic age estimation. Global hypermethylation due to relatedness was considerably higher than hypomethylation, was more pronounced in the male offspring, and mainly affected chromosomal loci associated with development. A relatedness-associated methylation signature was described that predicts parental relatedness with high accuracy, providing the proof of concept that kinship relationships can be inferred by epigenetic analyses. These findings identify parental relatedness as a modifier of epigenetic aging and global methylation, suggesting that kinship relations should be considered when epigenetic, and potentially transcriptomic data are interpreted in the context of aging and of other pathophysiological processes.

platform_organism:
Homo sapiens
Mus musculus
Rattus norvegicus

overall_design: The study involved ninety-six (96) tail specimens from a closed colony of Peromyscus maniculatus (North American deer mouse) of ages 1.3-33 months and variable degrees of parental relatedness (kinship) that was calculated by pedigree analysis. Animals were obtained by the Peromyscus Genetic Stock Center of the University of South Carolina and maintained under standard chow diet. Samples were assayed for genome wide DNA methylation. The aim of the study was to explore if parental kinship influences DNA methylation profiles and epigenetic age predictions.

first: Hippokratis

last: Kiaris


title: Single-cell multi-omic and multi-region atlas of the Aging Male Mouse Brain

city: La Jolla

first: Joseph

middle: R

last: Ecker

address: 10010 North Torrey Pines Road

department: Genomic Analysis Laboratory

institute: HHMI-Salk-Institute

type: Methylation profiling by high throughput sequencing

summary: Aging is the primary risk factor for many neurodegenerative diseases, primarily attributed to progressive changes in cellular epigenomes. Despite this known association, the complexity of the mammalian brain complicates the identification of brain regions and cell types that are most susceptible to aging effects. While alterations in gene expression have been observed in aging neural cells, comprehension of the epigenetic regulatory mechanisms underlying the transcriptomic changes remains largely elusive.  To unveil these complexities in a comprehensive manner, we utilized single-nucleus methylome sequencing (snmC-seq3) and multi-omic sequencing (snm3C-seq) to produce extensive datasets comprising 132,551 methylomes and 72,666 chromatin conformation-methylome joint profiles from eight distinct brain regions of C57BL/6J mice aged 2, 9, and 18 months. These regions include the anterior hippocampus (AHC), posterior hippocampus (PHC), frontal cortex (FC), amygdala (AMY), nucleus accumbens (NACB), PAG/PCG, entorhinal cortex (ENT), and caudate putamen (CP). We utilized this dataset to investigate age-related changes in DNA methylomes and transcription factor motifs potentially affected by methylation alterations. We also examined methylation changes in transposable elements, observing locus-specific retrotransposon activation. At the chromatin conformation level, we analyzed aging-related changes in compartmentalization, topologically associating domains (TADs), and chromatin loops. Furthermore, we explored regional heterogeneity during aging within identical cell types and validated our findings using the MERFISH dataset.

overall_design: C57BL/6J (males and females) mice of different ages were purchased from Jackson Laboratories and maintained in the Salk animal barrier facility on 12-hour dark-light cycles with food ad-libitum for up to 4 weeks (Housing condition: Temperature: 21-23 °C, relative humidity: 61-63%). Brains were extracted, sliced, and dissected in an ice-cold dissection buffer as previously described (Liu et. al. 2021). Females were synchronized for their estrous cycle by exposing them to male bedding for three days, and collected during diestrus. For snmC-seq3 and snm3C-seq samples, brains were sliced coronally at 600 μm intervals from the frontal pole across the whole brain, yielding 18 slices, and dissected brain regions were obtained according to the Allen Brain Reference Atlas Common Coordinate Framework version 3 (CCFv3) as previously described (Liu et. al. 2023). For nuclei isolation, each region was dissected from 2-7 animals and pooled to make 2-3 biological replicates. No statistical methods were used to predetermine sample size. We empirically determined to use two to three biological experiments for all single-cell epigenomic experiments to achieve minimum reproducibility for this large-scale project. Blinding and randomization is not performed during handling the tissue samples. Additionally, all dissected regions were digitally registered into CCFv3 using ITK-SNAP60 (v4.0.0) at a 25 μm resolution.

first: Qiurui

last: Zeng

first: Wei

last: Tian

first: Anna

last: Bartlett

last: Nery

first: Rosa

last: Gomez Castanon

first: Julia

last: Osteen

first: Jordan

last: Altshul

first: Nicholas

middle: D

last: Johnson

first: Mia

last: Kenworthy

first: Cynthia

last: Valadon


title: Dietary folic acid prevents peripheral neuropathy in mouse models of neural tube defects and type 2 diabetes

status: Public on Dec 17 2025

city: Schwerzenbach

first: Adhideb

last: Ghosh

address: Schorenstrasse 16

department: Health Sciences and Technology

country: Switzerland

institute: ETH Zurich

summary: Folate-mediated one-carbon metabolism is implicated in several pathologies including neural tube defects (NTDs), cancer and neurodegenerative disorders, whereas diabetes is associated with NTDs and peripheral neuropathy (PN). The development of peripheral neuropathy was assessed in Shmt1+/- and Shmt1 -/- mice, which are models of human folic acid-responsive NTDs, and diabetic (Leprdb) mice to determine if NTDs and PN have a shared etiology. From 6 weeks of age, male and female mice with reduced Shmt1 expression exhibited PN, with greater severity in females compared to males. The neuropathic progression was distinct from diabetic peripheral neuropathy (DPN) observed in Leprdb mice. Excess dietary folic acid prevented PN in both Shmt1-/- and Leprdb/db mice, whereas dietary uridine caused demyelinating PN in mice independent of genotype and folate status. The transcriptome from L3-L5 dorsal root ganglia (DRG) exhibited distinct sex-specific differences in glial cell gene expression when comparing Shmt1+/+ and Shmt1-/- mice. DRG sensory neurons exhibited changes in the expression of solute carriers and ion channels involved in nociception, neurotransmission and structural support. We conclude that reduced thymidylate synthesis causes folic-acid responsive NTDs and PN in mice, and that diabetes sensitizes mice to folic acid-responsive PN. Diabetes induces a special nutritional requirement for high intake of folic acid to prevent PN.

overall_design: For the RNA-seq experiments, wild type (Shmt1+/+) and knockout (Shmt1-/-) female and male mice were randomly weaned to AIN-93G (control) diet. For the rescue arm of the study, Shmt1-/- female mice were weaned to AIN-93G diet supplemented with 8mg/kg Folic Acid (excess FA) diets. The number of mice in each diet group were 5. After six months, dorsal root ganglions (DRGs) were surgically extracted from left and right sides of L3-L5 region of the spinal column. Total mRNA was extracted from the combined L3-L5 DRGs from each mice and represent an individual data point replicate in the RNA-seq data for analysis.

first: Joydeep

last: Chakraborty

first: Eunice

middle: B

last: Awuah

first: Sally

middle: P

last: Stabler

first: Martha

middle: S

last: Field

first: Regan

middle: L

last: Bailey

first: Patrick

last: Stover


title: Early-life NAD⁺ deficiency programs skeletal muscle aging via epigenetic downregulation of hyaluronic acid synthesis

status: Public on Dec 16 2025

city: Toyama

first: Jun-Dal

last: Kim

state: Toyama

address: 2630 Sugitani

department: Department of Complex Biosystem Research (CBR), Institute of National Medicine (INM)

country: Japan

institute: University of Toyama

summary: Nicotinamide adenine dinucleotide (NAD+) levels decline with age, which has been associated with the development of aging-associated diseases. However, it remains unknown whether low NAD+ levels in early life affect aging. This study demonstrates that deficiency of NAD synthetase (NADS), a critical enzyme of the deamidated NAD+ biosynthesis pathway, drastically reduced NAD+ levels in skeletal muscle and impaired muscle function at a young age. Intriguingly, NAD+ levels were restored to normal in middle-aged NADS knockout mice, whereas muscle function remained compromised. Gene expression analysis identified that hyaluronic acid synthase 2 (Has2) was downregulated in both young NADS knockout mice and aged wild-type mice. We also revealed that Has2 was epigenetically downregulated via the α-ketoglutarate-JMJD3 axis. Then, impaired hyaluronic acid signaling dampened muscle stem cell, leading to decreased locomotor activity. These results suggest that maintaining NAD+ levels during early life is important for promoting healthy aging in skeletal muscle.

overall_design: ChIP sequencing with anti-H3K27me3 antibody using the skeletal muscle samples from young WT and NADS KO mice.

first: Mariam

last: Karim

first: Takashi

last: Nakagawa


title: Differential Cellular Mechanisms Underlie Language and Executive Decline in Amyotrophic Lateral Sclerosis [Visium spatial transcriptomics]

city: New York

first: Christopher

last: Jackson

address: 101 Avenue of the Americas

department: Center for the Genomics of Neurodegenerative Disease

institute: New York Genome Center

summary: Half of all amyotrophic lateral sclerosis (ALS) patients demonstrate a spectrum of cognitive and behavioral changes over the course of the disease, but the mechanisms underlying this heterogeneity remain unclear. We assemble a high-resolution cellular map of prefrontal cortex regions of the ALS brain by integrating spatial and single-nucleus transcriptomic profiles of a cognitively stratified ALS patient cohort that includes non-neuropathological controls. We find cellular programs characteristic of ALS, including a frequent gliotic response. We also find that executive and language cognitive impairments differ from ALS without cognitive impairment, and from each other, in the extent and pattern of neuronal dysregulation and neuron-glial interactions across different brain regions. These findings reveal a relationship between cognitive phenotype and prefrontal cortex dysfunction in ALS.

overall_design: 246 10x Visium spatial transcriptomic libraries generated from 64 human donor prefrontal cortex samples (BA44/45 and BA46), across a range of non-neuropathological sudden-death controls, ALS patients, and ALS patients who exhibit cognitive impairment on a standardized screening exam

first: C

first: A

last: Daly

last: Roque

first: J

last: Petrescu

first: H

last: Phatnani


title: Enteric adenovirus antibody reactivity in year-1 infant serum measured using a protein microarray

city: Charlottesville

first: Jennifer

last: Hendrick

state: VA

address: 345 Crispell Drive

department: Medicine, Division of Infectious Diseases

institute: University of Virginia

summary: Processed and raw enteric adenovirus protein microarray reactivity data from 119 year-1 infant serum samples from a Bangladeshi birth cohort, with sample-level metadata aligned to Table 1 of the associated manuscript (Hendrick J, et al. J Infect Dis. 2025; jiaf558. doi:10.1093/infdis/jiaf558).

overall_design: Infant serum samples collected at ~1 year of age were probed on a multi-adenovirus protein microarray containing AdV 40/41 and related serotypes. Normalized IgG signal intensities were analyzed to identify antibody targets associated with protection from AdV 40/41 infection in year 2. Children were grouped by AdV 40/41 infection status in year 1 and year 2 (Y1+Y2-, Y1-Y2+, Y1+Y2+, Y1-Y2-).


title: Diurnal Light Transitions in Chlamydomonas reinhardtii

city: Berkeley

first: Sean

middle: D.

last: Gallaher

state: California

address: 176 Stanley Hall, room 408

department: California Institute for Quantitative Biosciences

institute: UC Berkeley

summary: For the model alga Chlamydomonas, acclimation to diurnal low light (LL) or high light (HL) results in changes in photosynthetic complexes, chlorophyll content, thylakoid membrane architecture, and nonphotochemical quenching capacity that are maintained through the intervening night phases. To determine how diurnal photoacclimation influences algal fitness and document the molecular events during reacclimation upon a change in daylight intensity, we transitioned LL-acclimated populations to diurnal HL and HL-acclimated populations to diurnal LL and performed an RNA-Seq timecourse over two diurnal periods.

overall_design: Cells were grown photoautotrophically in turbidostat photobioreactors under diurnal cycles of 12 h light at 28°C and 12 h dark at 18°C for a minimum of two weeks in order to establish population synchrony and acclimate them to either LL (50 PFD) or HL (1000 PFD). Then, the LL-acclimated populations were subjected to diurnal HL conditions, and the HL-acclimated populations were subjected to diurnal LL conditions. Cell physiology (cell number, size, pigments, photosynthetic parameters), the transcriptome, and the proteome were monitored for two diurnal periods. Samples were collected for RNA-Seq every 2 h.

first: Sunnyjoy

last: Dupuis

first: Victor

last: Zhong

first: Sabeeha

last: Merchant


title: Transcriptomic changes in the hypothalamus of gasping mice by high concentration of sevoflurane.

summary: Gasping respiration is a terminal pattern that occurs after anoxia effort in response to severe hypoxia, and has been known to increase the chances of survival in patients with cardiac arrest. During severe hypoxia, increased activity of upper airway muscles would be essential for self-resuscitation in association with gasping respiration. Previously, we reported that high concentration of sevoflurane, one of the volatile anesthetics, causes a gasping-like respiration pattern in mice. Herein, to extend understanding of the molecular mechanism involving the gasping respiration, we performed a comprehensive analysis of the changes in hypothalamic transcripts of sevoflurane-induced gasping mice.

overall_design: mRNA profiles of hypothalamic tissues were generated by RNA sequencing using the NextSeq 500 (Illumina).

first: Yoko

last: Irukayama-Tomobe

first: Koichiro

last: Tatsumi


title: Comparative Analysis of microRNA Expression in Serum and Plasma in Patients Screened for BRCA1/2 Mutations, dataset 2

city: Lodz

first: Urszula

last: Smyczynska

address: 15, Mazowiecka Street

department: Department of Biostatistics and Translational Medicine

country: Poland

institute: Medical University of Lodz

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

summary: Serum samples from 94 healthy women were analyzed using a custom qPCR panel comprising 182 miRNAs. Since this experiment is part of a broader study on miRnome alterations associated with BRCA mutations or BRCA-related cancers (particularly ovarian and breast cancer), 37 of the analyzed samples came from patients with BRCA1 mutations and 19 from BRCA2 mutation carriers. This analysis was preceded by sequencing-based quantification on the same set of the samples, the results of which are submitted separately to GEO under accession number GSE299787. The generation of this dataset was supported by The Gray Foundation grant “Circulating microRNAs for assessment of risk beyond the BRCA genes and early detection of breast cancer in high-risk families” awarded to Dipanjan Chowdhury, and by the National Science Centre (Poland) OPUS grant “Predictive Potential of Circulating MicroRNA Biomarkers in Patients with High Familial or Genetic Risk of Cancer” (2023/49/B/NZ5/03835) awarded to Wojciech Fendler.

overall_design: A custom PCR panel comprising 186 miRCURY LNA miRNA PCR Custom assays was used. miRNAs detected in at least 50% of the samples were kept in analysis. Normalization was based on the mean of Cq values of miRNAs detected in all samples in a set. dCq values were calculated as the difference between the global mean Cq of a given sample and the Cq of the miRNA of interest. Correlation analyses were used to assess similarities and differences in miRNA abundance between qPCR and sequencing.

last: Smyczyńska

first: Wojciech

last: Fendler

first: Dipanjan

last: Chowdhury

first: Aleksander

last: Rycerz


title: Comparative Analysis of microRNA Expression in Serum and Plasma in Patients Screened for BRCA1/2 Mutations, dataset 1

summary: Paired serum and plasma samples from 23 patients were analyzed using a custom qPCR panel comprising 182 miRNAs. Since this experiment is part of a broader study on miRnome alterations associated with BRCA mutations or BRCA-related cancers (particularly ovarian and breast cancer), 17 of the analyzed samples came from patients with BRCA1/2 mutations. This analysis was preceded by sequencing-based quantification on a larger set subset of the samples, the results of which are submitted separately to GEO under accession number GSE299150. The generation of this dataset was supported by The Gray Foundation grant “Circulating microRNAs for assessment of risk beyond the BRCA genes and early detection of breast cancer in high-risk families” awarded to Dipanjan Chowdhury, and by the National Science Centre (Poland) OPUS grant “Predictive Potential of Circulating MicroRNA Biomarkers in Patients with High Familial or Genetic Risk of Cancer” (2023/49/B/NZ5/03835) awarded to Wojciech Fendler.

overall_design: miRCURY LNA miRNA PCR Custom panel with 182 miRNA was used. miRNAs detected in at least 50% of the samples of either serum or plasma were included in the final analysis. Normalization was based on the mean of Cq values of miRNAs detected in all samples in a set. dCq values were calculated as the difference between the global mean Cq of a given sample and the Cq of the miRNA of interest. Differential expression and correlation analyses were used to assess similarities and differences in miRNA abundance between plasma and serum.


title: Comparative Analysis of microRNA Expression in Serum and Plasma in Patients Screened for BRCA1 or BRCA2 Mutations - dataset 3 part 1

summary: This dataset consists of miRNA expression in plasma of 78 women with germline BRCA1/2 mutations and expression in serum of 11 of them. Serum samples of remaining 67 women have been already submitted to GEO in GSE226445 dataset and to SRA as Bioproject PRJNA898621, while counts generated in re-mapping for this project are deposited as GSE299846 data set. MicroRNA abundance was quantified with sequencing in both biological materials. Data was analyzed with the aim of assessing the impact of blood processing steps on quantified miRNA abundance. Generation of this dataset was supported by The Gray Foundation grant “Circulating microRNAs for assessment of risk beyond the BRCA genes and early detection of breast cancer in high-risk families” awarded to Dipanjan Chowdhury and Polish National Research Center grant OPUS “Predictive Potential of Circulating MicroRNA Biomarkers in Patients with High Familial or Genetic Risk of Cancer” (2023/49/B/NZ5/03835) awarded to Wojciech Fendler.

overall_design: The experiment was performed in 78 pairs of human plasma and serum samples. All plasma samples belong to this submission, while in the case of serum 67 samples have been submitted previously, while the remaining 11 belong to this submission. All patients were female carriers of BRCA1/2 mutations, among them 1 had breast cancer at sample collection, 3 had ovarian cancer, 74 were healthy.


title: Comparative Analysis of microRNA Expression in Serum and Plasma in Patients Screened for BRCA1 or BRCA2 Mutations - dataset 1

summary: This dataset was created in order to evaluate the concordance of miRNA expression between serum and plasma in humans. miRNA expression was quantified in both biological materials using sequencing. Differential expression and correlations analysis were used to evaluate similarities and differences between miRNAs abundance in plasma and serum. Concurrently, miRNA quantification in the subset of these samples was performed by qPCR, the results of which belong to the separate submission to GEO. Generation of this dataset was supported by The Gray Foundation grant “Circulating microRNAs for assessment of risk beyond the BRCA genes and early detection of breast cancer in high-risk families” awarded to Dipanjan Chowdhury and Polish National Research Center grant OPUS “Predictive Potential of Circulating MicroRNA Biomarkers in Patients with High Familial or Genetic Risk of Cancer” (2023/49/B/NZ5/03835) awarded to Wojciech Fendler.

overall_design: The experiment was performed in 30 pairs of human serum and plasma samples collected at the same time. Each sample title indicates the patient, so pairs of samples are identified. All samples came from healthy women, but some of them harbored germinal BRCA1/2 mutations as this experiment is a part of a larger study about changes in miRnome induced by BRCA mutations or the presence of BRCA-related cancers (especially ovarian and breast cancer).


title: Comparative Analysis of microRNA Expression in Serum and Plasma in Patients Screened for BRCA1 or BRCA2 Mutations - dataset 3 part 2

summary: This dataset consists of miRNA expression in serum of 69 women. This data is the result of remapping raw sequencing FASTQ files being a part of the GSE226445 dataset and the SRA Bioproject PRJNA898621. MicroRNA abundance was quantified by sequencing. Data was analyzed together with plasma samples of those same patients with the aim of assessing the impact of blood processing steps on quantified miRNA abundance. Plasma data belongs to a separate submission (accession will be added when issued). Generation of this dataset was supported by The Gray Foundation grant “Circulating microRNAs for assessment of risk beyond the BRCA genes and early detection of breast cancer in high-risk families” awarded to Dipanjan Chowdhury and Polish National Research Center grant OPUS “Predictive Potential of Circulating MicroRNA Biomarkers in Patients with High Familial or Genetic Risk of Cancer” (2023/49/B/NZ5/03835) awarded to Wojciech Fendler.

overall_design: The whole experiment was performed in 78 pairs of human plasma and serum samples. This submission contains data from 69 serum samples with raw FASTQ files already deposited to SRA as Bioproject PRJNA898621. The difference between this dataset and previous one lays in data processing procedures, namely here sequencing data was mapped with version 2.3.0 of nf-core/smrnaseq for compatibility with newer plasma dataset, while GSE226445 contains counts generated by version 1.1.0. Remaining serum and plasma samples belong to separate submission. All 69 sample donors were healthy, female carriers of BRCA1/2 mutations.


title: Dicer accumulates in cytoplasmic foci upon alphavirus infection and plays a proviral role in Myotis myotis bat cells

city: Strasbourg

first: Sébastien

last: Pfeffer

address: 2 allée Konrad Roentgen

department: UPR 9002 - Architecture et Réactivité de l'ARN

institute: CNRS - Institut de Biologie Moléculaire et Cellulaire (IBMC)

summary: Bats are reservoirs for many viruses that frequently cause epidemics in humans and animals. It is thus critical to better understand their immune system and mechanisms of antiviral immunity. Despite an increasing number of studies, much is still unknown about the molecular mechanisms that govern bat-virus interactions, especially given the large diversity of bat species. Dicer is a conserved ribonuclease with multiple activities that can modulate antiviral immunity, including the detection of viral RNA as part of the RNA interference (RNAi) pathway, the maturation of micro RNAs, and the direct inhibition of innate immunity in mouse and human cells. In view of these complex activities of Dicer, we tested its antiviral activity in Myotis myotis nasal epithelial cells. Surprisingly, we did not see strong evidence of RNAi in these cells, but instead saw a proviral effect of Dicer for two alphaviruses, Sindbis and Semliki forest virus. We also observed a striking relocalization of Dicer to cytoplasmic foci upon infection with these viruses, which did not occur in the several human cell lines we tested. These foci contained dsRNA and viral plus strand RNA, suggesting that they are sites of viral replication. Finally, we found that factors specific to M. myotis cells are needed for Dicer relocalization. Overall, we propose that Dicer can play different roles in different bat species and/or cell types, and is being repurposed by alphaviruses to promote viral replication.

sample_organism:
Homo sapiens
Myotis myotis

platform_organism:
Homo sapiens
Myotis myotis

overall_design: SmallRNA sequencing were performed in M. myotis nasal epithelial cells either infected with Sindbis virus (SINV) or Semliki forest virus (VSV). As control, the same procedure was applied with human HEK293T cells, previously showed for not displaying a very strong RNAi signature against SINV (Girardi et al., 2013). Reads were aligned against their respective host genomes and all sequences that failed to map were used for a new alignment against SINV-GFP or VSV-GFP genomes. siRNA signatures were research on 22nt viral reads.

first: Léa

last: Gaucherand

first: Hugo

last: Marie

first: Julie

last: Cremaschi


title: Comparative Analysis of microRNA Expression in Serum and Plasma in Patients Screened for BRCA1 or BRCA2 Mutations - dataset 2

summary: This dataset contains serum miRNA expression of 94 healthy women, among which 56 harbored germline BRCA1 or BRCA2 mutations. MicroRNA abundance was quantified with sequencing and qPCR, the latter being the subject of separate GEO submission. Data was analyzed with the aim of assessing concordance between two miRNA assays and the possibility of translating miRNA biomarkers from sequencing to qPCR panel. Generation of this dataset was supported by The Gray Foundation grant “Circulating microRNAs for assessment of risk beyond the BRCA genes and early detection of breast cancer in high-risk families” awarded to Dipanjan Chowdhury and Polish National Research Center grant OPUS “Predictive Potential of Circulating MicroRNA Biomarkers in Patients with High Familial or Genetic Risk of Cancer” (2023/49/B/NZ5/03835) awarded to Wojciech Fendler.

overall_design: The experiment was performed in 94 samples of human serum. All samples came from healthy women, but 56 of them were carriers of germinal BRCA1/2 mutations as this experiment is a part of a larger study about changes in miRnome induced by BRCA mutations or the presence of BRCA-related cancers (especially ovarian and breast cancer). In this technical comparison between miRNA quantification methods we included only cancer-free individuals.


title: Spatially resolved integrative analysis of transcriptomic and metabolomic changes in tissue injury studies

status: Public on Dec 15 2025

city: Mölndal

first: Benjamin

last: Keith

address: Pepparedsleden 1

country: Sweden

institute: AstraZeneca

summary: Recent developments in spatially resolved -omics have enabled studies linking gene expression and metabolite levels to tissue morphology, offering new insights into biological pathways. By capturing multiple modalities on matched tissue sections, one can better probe how different biological entities interact in a spatially coordinated manner. However, such cross-modality integration presents experimental and computational challenges. To align multimodal datasets into a shared coordinate system and facilitate enhanced integration and analysis, we propose MAGPIE (Multi-modal Alignment of Genes and Peaks for Integrated Exploration), a framework for co-registering spatially resolved transcriptomics, metabolomics, and tissue morphology from the same or consecutive sections. We illustrate the generalisability and scalability of MAGPIE on spatial multi-omics data from multiple tissues, combining Visium with both MALDI and DESI mass spectrometry imaging. MAGPIE was also applied to newly generated multimodal datasets created using a specialised experimental sampling strategy to characterise the metabolic and transcriptomic landscape in an in vivo model of drug-induced pulmonary fibrosis and to showcase the linking of small-molecule co-detection with endogenous responses in lung tissue. MAGPIE highlights the refined resolution and increased interpretability of spatial multimodal analyses in studying tissue injury, particularly in pharmacological contexts, and offers a modular, accessible computational workflow for data integration.

overall_design: A male Wistar Han rat (n=1) was subjected to daily inhalation exposure via snout-only administration for 14 days with 15 mg/kg/day of the AZX test formulation of AZX (10%), MPEG-2000-DSPE (1.25%), trileucine (5%), and trehalose (83.75%), in a flowpast exposure chamber. The rat was purchased from Charles River (Germany) at 7 weeks and were 10 weeks at the start of dosing. Animal handling conformed to standards established by the Council of Europe ETS123 AppA, the Helsinki Convention for the Use and Care of Animals, Swedish legislation, and AstraZeneca global internal standards. All mouse experiments were approved by the Gothenburg Ethics Committee for Experimental Animals in Sweden and conformed to Directive 2010/63/EU. The present study was approved by the local Ethical committee in Gothenburg (EA000680-2017) and the approved site number is 31-5373/11.

first: Eleanor

last: Williams

first: Lovisa

last: Franzén

first: Martina

last: Olsson Lindvall

first: Gregory

last: Hamm

first: Steven

last: Oag

first: Muntasir Mamun

last: Majumder

first: James

last: Denholm

first: Azam

last: Hamidinekoo

first: Javier

last: Escudero Morlanes

first: Marco

last: Vicari

first: Joakim

last: Lundeberg

first: Laura

last: Setyo

first: Trevor

last: Godfrey

first: Livia

last: Eberlin

first: Aleksandr

last: Zakirov

first: Jorrit

last: Hornberg

first: Marianna

last: Stamou

first: Patrik

last: Ståhl

first: Anna

last: Ollerstam

last: Tan

first: Irina

last: Mohorianu


title: A Microphysiological Model of Human MASLD Reveals Paradoxical Response to Resmetirom

first: Dominick

last: Hellen

state: MA

address: 32 Vassar St

institute: Massachusetts Institute of Technology

summary: Metabolic dysfunction-associated steatotic liver disease (MASLD) is a chronic disease with multiple etiologies, stemming from the interplay between local and systemic genetic, diet, and gene-environment interactions. To understand the progression of MASLD in a controlled setting, we utilized a human liver microphysiological system (MPS) to establish a physiologically relevant metabolic baseline and probe how primary human hepatocytes respond to perturbations in insulin, glucose, and free fatty acids (FFAs). Replicate liver MPS were maintained in media with either 200 pM or 800 pM insulin for up to 3 weeks alone and in combination with standard glucose (5.5 mM), hyperglycemia (11 mM glucose), normal (20µM) and elevated FFA (100 µM). Together, hyperinsulinemia along with elevated glucose and FFAs, induces the release of pro-inflammatory chemokines, accumulation of triglycerides, and predisposes hepatocytes to insulin resistance. Treatment with the thyroid receptor ß agonist resmetirom normalizes hepatic fat content and partially rescues insulin sensitivity, but paradoxically induces higher CXCL1 and IL8 expression in male and female donors. In aggregate, our enhanced in vitro MPS model establishes a metabolic baseline and perturbed condition that recapitulates a spectrum of phenotypes observed in MASLD, offering improved quantification and insight into disease progression with relevance to human physiology.

overall_design:
Microphysiological modeling of MASLD with human hepatocytes in the CN-Bio LiverChip system.

*** Raw data not provided due to the human cells, along with their sequencing data, were provided as part of a contractual agreement and data-ownership restriction between an organization (NovoNordisk) and MIT. The raw sequencing data are owned and controlled by the sponsor in this case. Under this contract, we are able to share processed, non-identifiable gene-level count data. ***

first: Jessica

last: Ungerleider

first: Erin

last: Tevonian

first: Pierre

last: Sphabmixay

first: Priyatanu

last: Roy

first: Nikolaos

last: Meimetis

first: Federico

last: Presutti

first: Ashleigh

last: Williams

first: Ryan

last: Ogi

first: Caroline

last: Lewis

first: Jacob

last: Jeppesen

first: Sixian

last: You

first: Damien

last: Demozay

first: Linda

last: Griffith


title: Transcriptomic landscape of human primary stromal cells upon therapy-induced senescence (genotoxic chemotherapy and ionizing radiation)

city: Shanghai

first: Yu

last: Sun

address: 320 Yueyang Rd, Life Sciences Building A #1508

department: Shanghai Institute of Nutrition and Health

institute: Chinese Academy of Sciences

summary: Cellular senescence is a permanent state of cell cycle arrest that promotes tissue remodeling during embryonic development and after trauma or injury, but can also contribute to the decline of organ regenerative potential and tissue normal function, to local and systemic inflammation, and to tumorigenesis in aged organisms. For years, the identification, characterization, and pharmacological elimination of senescent cells have gained attention in the research field of aging and age-related diseases. However, the non-specificity of current senescence markers and the existence of different senescence programs strongly limit these tasks. Here, we profiled the genome-wide expression of primary normal human prostate stromal cells (PSC27) upon therapy-induced senescence (TIS), with the aim to determine molecular regulators of senescence phenotypes and define the inherent correlation of gene expression pattern with the extensive senescence-associated 3D genome reorganization. This TIS-specific configuration of chromosome architecture brings active genes located in genomic regions adjacent to senescence-associated heterochromatin domains (SAHDs) in close spatial proximity and favors their expression. These data may provide a baseline to further explore show how multi-omics and 3D mapping can identify critical features of cellular senescence and discover key determinants of senescence and SAHF formation in the genome-wide landscape.

overall_design: RNA-seq examination of genome-wide transcriptional changes of primary normal human prostate stromal cells (PSC27) in proliferating versus senescence phase generated by the chemotherapeutic agent bleomycin or gamma-ray ionizing radiation. .

first: Changxu

last: Wang


title: Opposing functions of distinct regulatory T cell subsets in colorectal cancer

first: Sneha

last: Mitra

address: 1275 York Avenue

institute: Memorial Sloan Kettering Cancer Center

summary: Regulatory T (Treg) cells are considered major contributors to the growth of solid organ tumors, with the notable exception of colorectal cancer (CRC), despite the documented abundance of Treg cells in CRC. Here, we demonstrate that IL-10⁺ and IL-10⁻ Treg cells constitute two distinct subsets with opposing functions: IL-10⁺ Treg cells counteract, while IL-10⁻ Treg cells promote, the growth of genetically engineered CRC tumors. Our findings suggest that the tumor-suppressive function of IL-10⁺ Treg cells is mediated by their suppression of effector CD4⁺ T cell production of IL-17, a cytokine that directly stimulates CRC tumor cell proliferation. Consistently, IL-10⁺ Treg cells were more abundant in both mouse and human CRC tumors than in tumor-adjacent normal colon tissue, whereas IL-10⁻ Treg cells exhibited the opposite distribution. Furthermore, gene expression signatures associated with IL-10⁺ and IL-10⁻ Treg cells correlated with better and worse disease prognoses in human CRC, respectively. This functional dichotomy between Treg subsets provides a rationale for therapeutic strategies aimed at selectively targeting pro-tumoral Treg cells while preserving their anti-tumoral counterparts across various barrier tissue cancers that harbor both subsets.

overall_design: RNA-seq profiling of tumors from locally advanced rectal cancer (stage II-III) patients.

first: Xiao

last: Huang

first: Dan

last: Feng

first: Emma

last: Andretta

first: Nima

last: Hooshdaran

first: Aazam

last: Ghelani

first: Eric

middle: Y

first: Joe

middle: N

last: Frost

first: Victoria

last: Lawless

first: Aparna

last: Vancheswaran

first: Qingwen

last: Jiang

first: Christina

last: Leslie

first: Alexander

last: Rudensky


overall_design: Single-cell multi-ome data (ATAC-seq and nuclear RNA-seq) of T cells sorted from mouse AKP tumor and normal adjacent tissue samples 4 weeks after transplantation.


title: Altered MDC1 Interactions and Dysfunctional DNA Repair in Lobular Breast Cancer Confers Sensitivity to PARP Inhibition

city: AURORA

first: Etienne

last: Danis

state: CO

department: Cancer Center

institute: University of Colorado, Denver - Anschutz Medical Campus

summary: Invasive lobular carcinoma of the breast (ILC) is typically estrogen receptor α (ER)-positive and presents with biomarkers of anti-estrogen sensitive disease. Unfortunately, patients with ILC face particularly poor long-term outcomes with high recurrence risk, suggesting a divergent endocrine response and ER function in ILC compared to other breast cancers. ER is co-regulated by the DNA repair protein MDC1 specifically in ILC cells, driving distinct ER activity. Here, we profiled the MDC1 interactome to examine how MDC1 regulates ER activity and DNA repair function in ILC. MDC1-associated proteins in ILC cells mirrored a “BRCA-like” state lacking key homologous recombination (HR) proteins, consistent with HR dysfunction but distinct from classic “BRCAness”. Single-cell transcriptome and DNA repair activity analyses, along with DNA repair signaling and functional data, substantiated dysfunctional induction and execution of HR in ILC cells. In parallel, ILC tumor data were consistent with a form of HR dysfunction distinct from overt HR deficiency, lacking BRCA-like genomic scarring but showing elevated signatures of PARP inhibitor sensitivity. Treatment with the PARP inhibitor talazoparib produced a durable growth suppression both in vitro and in multiple ILC xenografts in vivo. Together, these findings reveal that ILC-specific ER:MDC1 activity comes at the cost of DNA repair dysfunction, which may be therapeutically targetable.

overall_design: ILC cell line MDA MB 134VI (MM134) was hormone-deprived, then treated with vehicle (0.01% EtOH) or estradiol (E2, 100nM) for 24 hours prior to sample collection. After treatment, single cell suspensions were prepared according to 10X Genomics recommendations; Haircut libraries were prepared as described (PMID: 32286626 and bioRxiv 2019.10.29.820233), and separate targeted capture libraries were prepared according to the manufacturer’s instructions (https://www.10xgenomics.com/products/targeted-gene-expression).

first: Matthew

last: Sikora

first: Joseph

last: Sottnik

first: Amanda

last: Richer

first: Rui

last: Fu

first: Jay

last: Hesselberth


title: In vivo screen reveals specific roles of Hippo pathway components in development and regeneration

city: Edinburgh

first: Carsten

middle: Gram

last: Hansen

address: 4-5 Little France Dr

department: Centre for Inflammation Research

institute: University of Edinburgh

summary: The Hippo signalling pathway is a major regulator of regeneration and development. However, the comparative importance and functional roles of individual Hippo pathway components in vivo is greatly unknown, particularly within the vertebrate lineage. To gain direct and comparable insights we took advantage of the zebrafish larvae model system. We generated individual and combined CRISPR/Cas9 F0 knockouts of a range of core Hippo pathway genes, including upstream regulators, the co-transcriptional regulators Yap1/Taz, and Yap1/Taz-target genes. We analysed and compared the resulting developmental and regenerative phenotypes. Our findings highlight that paralogues of core components have distinct, but in some instances overlapping, functions.  Intriguingly, we find that Yap and Taz have differential roles during development and regeneration. In addition, we characterise and compare two tail fin regenerative paradigms: after both severe and mild injury. These injury paradigms are drastically different and elicit diverse resolution processes. We confirm critical roles of the immune system in the regenerative process and identify that macrophages are recruited to lesser extent in tail fin regeneration upon Yap1 and Taz loss, suggesting defective regenerative macrophage function. This defective macrophage involvement might therefore be one of the mediators of the deficient regeneration in these two Crispants. Overall, our analysis emphasises distinct requirements and responses of the Hippo pathway during development and across different regenerative paradigms.

overall_design: Bulk RNA-seq of zebrafish tail fin tissue. Samples include uninjured and injured (severe tail fin injury paradigm tissue at 3dpf) tissue, from WT and Yap or Taz Crispant fish.

first: Susanna

middle: E

last: Riley

first: Michaela

last: Noskova

first: Shijia

last: Xia

first: Richard

last: Cunningham

first: Justyna

last: Cholewa-Waclaw

first: Yi

middle: G


first: Sneha

last: Mitra

overall_design: Mouse T cells and myelod cells were sort purified from transcplanted AKP tumor and the adjacent cecal tissue. Tissues were harvested from IL-10cre Foxp3 LSL-DTR mice treated with DT to deplete IL-10+ Treg cells, or bDT as control two weeks after tumor inoculation and DT/bDT treatment. DT/bDT treatments were done on Day 0, 1, 4, 7, 10, and 13.

first: Xiao

last: Huang

first: Dan

last: Feng

first: Emma

last: Andretta

first: Nima

last: Hooshdaran

first: Aazam

last: Ghelani

first: Eric

last: Wang

first: Joe

last: Frost

first: Victoria

last: Lawless

first: Aparna


title: FOLFIRINOX Plus Nivolumab Promotes Irregular Intra-Tumoral Lymphoid Aggregates in Borderline Resectable Pancreatic Adenocarcinoma: A Phase 1 Trial

status: Public on Dec 13 2025

first: Jason

middle: Michael

last: Link

address: 650 Charles E Young Dr S

department: Surgery

summary: Combination therapies of chemotherapy and immune checkpoint inhibitors (ICIs) have failed to improve survival in pancreatic ductal adenocarcinoma (PDAC), except in rare MSI-H cases, despite their success in other solid tumors.  Most prior studies have been conducted in advanced disease. Here, we present clinical, pathologic, and translational results from a phase 1b/2 investigator-initiated study evaluating neoadjuvant modified FOLFIRINOX (mFOLFIRINOX, mFFX) plus nivolumab in patients with borderline-resectable (BR) PDAC. Among 28 patients enrolled, 22 (79%) proceeded to surgery. Treatment was well tolerated with no significant delays or surgical complications, meeting the primary endpoint. Among patients who underwent surgical resection, median disease-free survival was 19.7 months, median progression-free survival was 26 months (95% CI: 14.7-34.3) and median overall survival was 38 months (95% CI: 27.9-not reached). The regimen demonstrated an acceptable safety profile, with all Grade 3-4 treatment-related adverse events due to chemotherapy and no Grade 3 immune related adverse events observed. Treatment effects were assessed using paired pre- and post-treatment samples and by comparing post-treatment tumors from the nivolumab cohort to historical BR mFFX-only controls. In paired analyses, intra-tumoral CD8 T cells and plasma cells increased together; in between-group comparisons, plasma cells were significantly higher in the nivolumab cohort, with a modest CD8 T cell increase. Immunohistochemistry revealed that plasma cell abundance correlated with dense intra-tumoral lymphoid aggregates (LA) lacking germinal center-like morphology, a pattern consistent with extrafollicular B cell differentiation. Single-cell spatial transcriptomics identified irregular lymphoid aggregates with high plasma cell to B cell ratios (PBRs) that were enriched for terminally exhausted CD8 T cells and de-enriched for progenitor exhausted CD8 T cells and central memory CD4 T cells. Together, these findings implicate intra-tumoral LA disorganization and skewed T cell subsets as complementary features associated with limited efficacy of PD-1-based chemoimmunotherapy in PDAC. (Clinicaltrials.gov identifier: NCT03970252).

overall_design: RNA-seq was performed on RNA extracted from 6 pre-treatment biopsies from patient primary pancreatic adenocarcinoma (PDAC) tumors, 21 post-treatment (FOLFIRINOX+nivolumab) primary PDAC tumors, and 9 post-treatment (FOLFIRINOX) primary PDAC tumors

first: Zev

last: Wainberg

first: Timothy

last: Donahue


title: RNAseq analysis of human neutrophils from healthy controls and from people with systemic lupus eruthematosus

city: Liverpool

first: Helen

middle: Louise

last: Wright

address: 6 West Derby Street

department: Institute of Life Course and Medical Sciences

institute: University of Liverpool

summary: We report gene expression profiles of blood neutrophils from (1) healthy adults (2) healthy pediatrics, (3) adults with SLE, (4) pediatrics with SLE. Participants were recruited from two sites, Liverpool UK or Bangkok, Thailand.

overall_design: Neutrophils (purity >97%) were isolated from peripheral blood by separation of leukocytes from erythrocytes using HetaSep, then centrifugation through density-gradient reagent (HetaSep). Remaining erythrocytes were removed by hypotonic lysis using ammonium chloride buffer. RNA was isolated using Trizol:chloroform, cleaned up by Qiagen RNeasy kit including on-column DNase digest and sequenced on the DNBseq platform.

first: Grace

last: Filbertine

first: Marie

last: Phelan

first: Direkrit

last: Chiewchengchol

first: Nattiya

last: Hirankarn


title: Differential Roles of Type I Topoisomerases in Regulating HPV Pathogenesis

status: Public on Dec 12 2025

city: Chiacgo

first: Arushi

last: Vats

state: Illinois

address: 320E Superior street

department: Microbiology-Immunology

institute: Northwestern University

summary: High-risk human papillomaviruses (HPVs) activate the ATM and ATR pathways by inducing DNA breaks through the action of viral oncoproteins E6 and E7, which target factors such as topoisomerases. Type I topoisomerases cleave and relegate a single strand of DNA, and little is known about how they regulate HPV pathogenesis. The levels of type I topoisomerases, TOP1A, TOP3A, and TOP3B, were all elevated in cells maintaining high-risk HPV genomes, as well as in squamous cell carcinomas. Only TOP1A and TOP3B, but not TOP3A, bound to HPV genomes and were critical for regulating viral gene transcription and replication with little effect on cell growth. Furthermore, the knockdown of TOP1A or TOP3B reduced levels of DNA breaks and differentially altered the expression of genes in key pathways. TOP1A knockdown reduced the expression of IL6 and activation of the pro-cytokine signaling pathway. In contrast, TOP3B targeted EGR3, which regulates growth and differentiation. Finally, TOP1A and TOP3B differentially regulate the formation of R-loops, which are critical for viral replication. These findings demonstrate the differential roles of type I topoisomerases in HPV pathogenesis.

overall_design: CIN 612 cells (keratinocytes isolated from a cervical biopsy that stably maintain the HPV 31 genome) were transduced with lentivirus to express either a scrambled sequence (Samples 1/2), shRNA targeting TOP1A (Samples 3/4), or TOP3B (Samples 5/6). RNA sequencing was performed on each of these samples and the scramble control CIN 612 cells were compared to CIN 612 cells depleted with TOP1A or TOP3B

first: Conor

middle: W

last: Templeton

first: Laimonis

last: Laimins


title: Comprehensive transcriptome analysis of skeletal muscle in the NADS knockout mice.

first: Jun-Dal

last: Kim

summary: Nicotinamide adenine dinucleotide (NAD+) is a pivotal molecule involved in various biological processes, including energy production, protein post-translational modification, DNA repair, calcium mobilization, and 5’-capping of mRNA. Accumulating evidence has revealed that NAD+ declines with age by disturbing the balance between its synthesis and degradation. Decreased NAD+ levels result in deterioration of physiological functions in multiple tissues, including the liver, muscle, kidney, and brain. Contrarily, the repletion of NAD+ levels by supplementation of NAD+ precursors have beneficial effects on lifespan, physiological aging, and aging-associated diseases. However, it is unknown whether declined NAD+ levels in young age affect aging processes. Therefore, in this study, to better understand the effect of NAD+ levels on the aging processes, we performed the RNA-sequencing using skeletal muscle samples from young and old wild-type and NAD synthetase (NADS)-deficient mice.

overall_design: mRNA profiles of  skeletal muscles were generated by RNA sequencing using the Illumina NovaSeq 6000  (Illumina).

first: Mariam

last: Karim

first: Takashi

last: Nakagawa


title: Systems Genetics of Lifespan and Senescence in Drosophila melanogaster

status: Public on Dec 11 2025

city: Greeenwood

first: Maryam

last: Nasiri Aghdam

address: 114 Gregor Mendel Cir

institute: Clemson University

summary: As global populations age, understanding the genetic basis of variation in lifespan becomes increasingly important. We used an outbred population derived from 37 inbred, sequenced lines from the Drosophila Genetic Reference Panel. We performed whole genome sequencing on pools of young and old flies, separately for males and females, to identify variants and genes associated with increased lifespan. We identified 742 variants in females and 428 in males, most of which were sex-specific; only 53 genes and 6 variants were shared between males and females, with some variants exhibiting sexually antagonistic patterns. Of the 1,117 mapped genes, 665 had human orthologs and many were associated with disease phenotypes. Gene Ontology analyses revealed enrichment for genes affecting nervous system development and mitochondrial functions. We conducted RNA sequencing of male and female heads, bodies, and reproductive tissues weekly up to 10 weeks of age. We identified nearly 2,600 genes with significant age-related changes, that were enriched in mitochondrial, metabolic, immune, and neuronal pathways. A total of 185 of these genes had variants associated with lifespan from the first study. Construction of interaction networks using all age-significant genes and their interacting partners revealed 25 xQTL-containing hub genes with human orthologs, including blw, klu, Dronc, ATP5PD, mEFTu1, levy, and Socs36E. Context-dependent correlation analysis revealed tissue- and sex-specific expression patterns among age-associated genes, highlighting xQTL genes with strong tissue-specific regulation. These findings illustrate how systems genetics can identify conserved pathways and candidate genes relevant to human aging and longevity.

overall_design: We used an outbred population derived from 37 sequenced inbred lines of the Drosophila Genetic Reference Panel. Whole-genome sequencing was performed on pooled young and old flies, separately by sex, to identify lifespan-associated variants and genes. Additionally, we conducted weekly RNA sequencing of male and female heads, bodies, and reproductive tissues up to 10 weeks of age.

first: Desiree

last: Unselt

first: Maria

last: Adonay

first: Tatania

middle: V

last: Morozova

first: Gunjan

middle: H

last: Arya

first: Lavanya

last: Turlapati

first: Vijay

last: Shankar

first: Robert

last: Anholt

first: Trudy

last: Mackay


first: Sneha

last: Mitra

overall_design: Single-cell multi-ome data (ATAC-seq and nuclear RNA-seq) of T cells sorted from human colorectal cancer tumor and normal adjacent tissue samples. T cells are sorted as live MHC-II- CD3+TCRb+.

first: Xiao

last: Huang

first: Dan

last: Feng

first: Emma

last: Andretta

first: Nima

last: Hooshdaran

first: Aazam

last: Ghelani

first: Eric

last: Wang

first: Joe

last: Frost

first: Victoria

last: Lawless

first: Aparna

last: Vancheswaran

first: Qingwen

last: Jiang

first: Christina

last: Leslie

first: Alexander

last: Rudensky


title: CD38 endows local antigen-specific Foxp3+ Treg cells with stress resilience for compartmentalized control of CNS inflammation

city: Munich

first: Thomas

last: Korn

email: thomas.korn@tum.de, c.sie@tum.de

address: Ismaninger Str. 22

department: Experimental Neuroimmunology

country: Germany

institute: Technical University of Munich

summary: Foxp3-expressing regulatory T (Treg) cells protect from systemic autoimmunity. However, little is known about the significance of Treg cells in inflammation-experienced tissues. Using experimental autoimmune encephalomyelitis (EAE), we show that Treg cells accumulate and persist in the central nervous system (CNS) until long after the resolution of the bulk of the inflammatory infiltrate. CNS-specific local depletion of post-inflammatory Treg cells, but not systemic depletion of Treg cells, immediately rekindles autoimmune inflammatory flares in the CNS by residual local effector T cells. Expression of the NAD-consuming ecto-enzyme CD38 is crucial for the functional adaptation of post-inflammatory CNS Treg cells to a stressful microenvironment, in which access to IL-2 is limited. CD38 counteracts ADP-ribosylation of the IL-2R and, thus, maintains its high sensitivity to IL-2. Their fully functional high-affinity IL-2 receptor prevents the loss of tissue-resident antigen-specific Treg cells. These "stress-tolerant" CNS Treg cells impede the collapse of immune homeostasis in the CNS once acute inflammation is controlled.

overall_design: We profiled the transcriptome of spleen, visceral adipose tissue, and CNS Foxp3+ Treg cells, along with Foxp3- conventional Th cells (Tconv), isolated from Foxp3 (GFP) reporter mice at different EAE disease stages (Naïve, Pre-onset, Peak, Recovery) using bulk RNA-seq. Additionally, we employed the same experimental design to isolate cells from Foxp3ERT2-Cre Rosa26LSL-tdTomato mice at the Recovery stage. Utilizing Tamoxifen labeling and the Foxp3 fate-mapping system, we sorted stable (Foxp3-GFP+, tdTomato+) and unstable (Foxp3-GFP+, tdTomato−) populations and performed bulk RNA-seq analysis.

first: Andreas

last: Muschaweckh

first: Hsin-Hsiang

last: Chen

first: Rupert

last: Öllinger

first: Christopher

last: Sie


first: Sneha

last: Mitra

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

overall_design: Refer to individual Series

first: Xiao

last: Huang

middle: R

first: Cheryl

last: Mai

first: Karuna

last: Ganesh


overall_design: Mouse T cells and myeloid cells were sort purified from transcplanted AKP tumor, liver metastases, and lymph node metastases ten weeks after tumor transplantation.

first: Dan

last: Feng

first: Emma

last: Andretta

first: Nima

last: Hooshdaran

first: Aazam

last: Ghelani


title: Whole-genome bisulfite sequencing of whole blood cells in dog lymphomas cases

city: Fujimino

first: Miyuki

last: Nakamura

state: Saitama

institute: KDDI research Inc

summary: DNA methylation patterns reflect the status of individual tissues in mammals, including factors such as cell composition, age, and local environment. These patterns can be leveraged to predict an individual's health status. The aim of this experiment is to discover the signature of lymphoma using DNA methylation from blood samples of dogs. We compared whole-genome DNA methylation data from individuals diagnosed with lymphoma to that from a control group. After adjusting for differences in age and breed, we detected differentially methylated regions.

overall_design: Whole-genome bisulfite sequencing was performed with whole blood obtained from twenty individual dogs diagnosed with lymphoma. The breeds of subjects were Poodle (Toy,Standard), Shiba, Dachshund (Miniature), Bichon Frise, Boston Terrier, Cavalier King Charles Spaniel, Chihuahua, French Bulldog, Golden Retriever, Norfolk Terrier, Papillon, Pug, Shetland Sheepdog, and Yorkshire Terrier.


title: Evaluation of the efficacy of radiodynamic therapy using talaporfin sodium in human pancreatic cancer MIA PaCa-2 xenograft models

city: Kitakyushu

first: Junko

last: Takahashi

state: Fukuoka

address: 2-7 Hibikino, Wakamatsu-ku

department: Graduate School of Information, Production and Systems

institute: Waseda University

summary: We investigated changes in gene expression in MIA PaCa-2 human pancreatic cancer xenografts in nude mice after radiodynamic therapy using talaporfin sodium.

overall_design:
MIA PaCa-2 human pancreatic cancer cells were implanted subcutaneously into immunodeficient mice to establish xenograft tumors.
Once tumors reached the experimental size, animals were randomly assigned to four treatment groups:
1. NT (control): no treatment.
2. TS: talaporfin sodium administration only.
3. XT: X-ray irradiation only.
4. TS-XT: combination of talaporfin sodium and X-ray irradiation.
Talaporfin sodium was administered intravenously at 10 mg/kg, 2 hours prior to each irradiation session.
X-ray irradiation was delivered at 3 Gy per day for three consecutive days (total dose = 9 Gy).
Tumors were excised 25 days after the final irradiation, and total RNA was extracted from each tumor.
RNA sequencing was performed to investigate changes in gene expression profiles among the four treatment groups.

first: Teppei

last: Yamaoka


title: scRNA-seq of MC38 syngeneic colorectal tumors after FAP-CAR mRNA-LNP therapy

status: Public on Dec 10 2025

city: Suita

first: Sikun

last: Meng

state: Osaka

address: Yamadaoka 2-2

institute: the Universiy of Osaka

summary: This study investigates the therapeutic potential of an mRNA–lipid nanoparticle (LNP)-based strategy delivering fibroblast activation protein (FAP)-specific chimeric antigen receptor (CAR) mRNA in colorectal cancer. Syngeneic colorectal mouse tumor models were treated with FAP-CAR mRNA-LNPs, and single-cell RNA sequencing (scRNA-seq) of tumor tissues was performed. The analysis aimed to explore mechanisms of tumor relapse following treatment, with a particular focus on the MIF–CD74 signaling axis. The data revealed heterogeneous immune and stromal cell states, highlighting immunosuppressive pathways associated with relapse.

overall_design: MC38 syngeneic colorectal tumors were established in C57BL/6 mice and treated with FAP-CAR mRNA-LNPs in combination with 5-fluorouracil (5-FU), anti-PD1, and anti-CTLA4 antibodies. Tumor tissues were collected from two relapse cases and one untreated control for single-cell RNA sequencing (scRNA-seq).

first: Tomoaki

last: Hara

first: Tetsuya

last: Sato

first: Shotaro

last: Tatekawa

first: Yasuko

last: Arao

first: Yoshiko

last: Saito

first: Toshiro

last: Hirai

first: Daisuke

last: Motooka

first: Sarah

last: Rennie

first: Taroh

last: Satoh

first: Kazuhiko

last: Ogawa

first: Yutaka

last: Miura

first: Masaki

last: Mori

first: Yuichiro

last: Doki

first: Hidetoshi

last: Eguchi

first: Hideshi

last: Ishii


title: CX-5461 and Doxorubicin activate a shared DNA damage–associated transcriptional response in human cardiomyocytes

city: Galveston

first: Michelle

middle: C.

last: Ward

address: 301 University blvd.

institute: UTMB

summary: CX-5461 (CX) is under investigation for the treatment of late-stage cancers. While CX was first described as an RNA polymerase I inhibitor, it has recently been shown to primarily inhibit the beta isoform of topoisomerase II. This isoform is also inhibited by anthracycline drugs including Doxorubicin (DOX) and mediates the toxic effects of these drugs on the heart. It is unclear whether CX will similarly cause cardiotoxicity. We therefore tested the effects of CX on iPSC-derived cardiomyocytes from six individuals. CX induces cell death in cardiomyocytes at micromolar concentrations. Transcriptome profiling following treatment over time reveals gene expression programs that correspond to the DNA damage response, which are pathways shared with DOX response genes. Micromolar CX concentrations affect heart-specific genes and 14 functionally-validated genes in loci associated with DOX cardiotoxicity. Our data demonstrate the impact of CX on the transcriptome of cardiomyocytes, a potential off-target cell type of the drug.

overall_design: We generated RNA-seq data from iPSC-derived cardiomyocytes differentiated from six healthy individuals, including three females (Individuals 1–3) and three males (Individuals 4–6). Cardiomyocytes were treated with 0.1 µM or 0.5 µM of CX-5461 (CX), Doxorubicin (DOX), or vehicle control (VEH) for 3, 24, or 48 hours.

first: Sayan

last: Paul

first: José

middle: A

last: Gutiérrez

first: Alyssa

last: Bogar

first: Renee

last: Matthews

middle: C


title: Socially Responsive Yolk Steroids Correlate with Early Extraembryonic Gene Expression

city: Bloomington

first: Center for Genomics and Bioinformatics

last: IU

state: IN

address: 1001 E Third St

department: Biology

institute: Center for Genomics and Bioinformatics

summary: Here, we identify socially sensitive yolk hormones and explore their relationship with transcript-wide gene expression patterns in extra-embryonic tissues during early embryonic development in male and female house sparrows (Passer domesticus). To enable the latter, we additionally characterized how yolk hormones change across development to identify the period during which maternally derived hormones are present. We exposed captive-breeding house sparrows to simulated territorial intrusions throughout the yolking period and collected eggs to measure >30 yolk hormones using LC-MS-MS. We additionally collected unmanipulated eggs from the aviary and the wild and incubated them to one of three timepoints: embryonic day 0 (ED0), ED3, or ED5. We characterized how yolk hormones changed across development and then explored relationships between transcript-wide gene expression levels in ED3 extra-embryonic tissues and levels of yolk hormones that are responsive to social stimuli.

overall_design: Eggs were unmanipulated and incubated to embryonic day (ED) 3 or 5. RNA was collected from extraembryonic and brain tissues.

first: Jasmeen

last: Kaur

first: Ryan

middle: T

last: Paitz

first: Taylor

last: Verrett

first: Alexandra

middle: B

last: Bentz


title: RNA-seq of colorectal cancer patient-derived xenograft (PDX) tumors treated with FAP-CAR mRNA-LNP therapy

first: Sikun

last: Meng

summary: This study investigates the therapeutic potential of an mRNA–lipid nanoparticle (LNP)-based strategy to deliver fibroblast activation protein (FAP)-specific chimeric antigen receptor (CAR) mRNA in colorectal cancer. Patient-derived xenograft (PDX) tumor models (PDX-1 and PDX-2) were treated by splenocytes with FAP-CAR mRNA-LNPs, including wild-type or 7SL1 knock-in splenocytes, in comparison with PBS controls. RNA sequencing of the tumor tissues was performed to profile transcriptional responses associated with treatment efficacy or resistance. Differential expression and pathway enrichment analyses revealed distinct immune and stromal gene programs, including HOX family transcription factor activation in resistant tumors.

overall_design: Tumor tissues were harvested from colorectal cancer PDX models following treatment with different regimens: PDX-1: PBS control vs. splenocytes + FAP-CAR mRNA-LNPs (with 7SL1 knock-in splenocytes). PDX-2: PBS control vs. splenocytes + FAP-CAR mRNA-LNPs (with wild-type splenocytes or 7SL1 knock-in splenocytes).

first: Tomoaki

last: Hara

first: Tetsuya

last: Sato

first: Shotaro

last: Tatekawa

first: Yasuko

last: Arao

first: Yoshiko

last: Saito

first: Toshiro

last: Hirai

first: Daisuke

last: Motooka

first: Sarah

last: Rennie

first: Taroh

last: Satoh


title: ATAC-seq of colorectal cancer patient-derived xenograft (PDX) tumors treated with FAP-CAR mRNA-LNP therapy

summary: This study investigates the therapeutic potential of an mRNA–lipid nanoparticle (LNP)-based strategy to deliver fibroblast activation protein (FAP)-specific chimeric antigen receptor (CAR) mRNA in colorectal cancer. Patient-derived xenograft (PDX) tumor models (PDX-1 and PDX-2) were treated by splenocytes (7SL1 knock-in) with FAP-CAR mRNA-LNPs, in comparison with PBS controls. ATAC sequencing of the tumor tissues was performed to profile transcriptional responses associated with treatment efficacy or resistance. Analysis revealed distinct chromatin accessibility programs, including activation of HOX gene clusters in resistant tumors, highlighting potential epigenetic mechanisms of therapeutic escape.

overall_design: Tumor tissues were harvested from colorectal cancer PDX models following treatment with different regimens: PDX-1: PBS control vs. splenocytes (7SL1 knock-in)  + FAP-CAR mRNA-LNPs. PDX-2: splenocytes (7SL1 knock-in) + FAP-CAR mRNA-LNPs.

first: Kazuhiko

last: Ogawa

first: Yutaka

last: Miura

first: Masaki

last: Mori

first: Yuichiro

last: Doki

first: Hidetoshi

last: Eguchi

first: Hideshi

last: Ishii


title: Functional interplay between (p)ppGpp and RNAP in Acinetobacter baumannii

city: Namur

first: Regis

last: Hallez

address: 61 Rue de Bruxelles

country: Belgium

institute: UNamur

summary: The (p)ppGpp-dependent stress response is required for pathogenic bacteria to survive both outside and inside the host but the mechanisms behind this survival are mostly unknown. In this study, we characterize the (p)ppGpp metabolism in the opportunistic pathogen multi-drug-resistant Acinetobacter baumannii. We show that two stressful conditions potentially encountered during infection – iron starvation and polymyxin exposure – induce (p)ppGpp production. The absence of (p)ppGpp led to multiple consequences on the physiology of A. baumannii, including an increase of surface motility, a decrease in catalase activity, a poor survival upon nutrient starvation, a rapid killing during desiccation and a strong attenuation in a Galleria mellonella model of infection. Using a motility suppressor screen, we isolated multiple independent stringent mutations in rpoB and rpoC that suppress the (p)ppGpp-dependent phenotypes. By combining the suppressor screen with deep sequencing, we isolated dozens of additional mutants, expanding the list of putative stringent RNAP mutations described so far. Furthermore, our transcriptomic data reveal that (p)ppGpp deeply impacts the transcriptional landscape of A. baumannii on solid surface to induce many stress-related genes, including catalase and hydrophilins critical for tolerance to desiccation. This work highlights the functional interplay between (p)ppGpp and RNAP in the successful survival of A. baumannii in the environment but also during infection.

overall_design: Determination of (p)ppGpp-dependent regulons in Acinetobacter baumannii WT, DrelA and DrelA rpoB_R557C suppressor mutant cells grown on LB low agar plates and in LB liquid medium

first: Anthony

last: Perrier

first: Aurélie

last: Budin-Verneuil

first: Régis