title: PUM2 knockdown regulates the expression and alternative splicing of genes associated with myocardial fibrosis in H9C2 cells

city: Urumqi City

first: Jie

address: No. 91, Tianchi Road

institute: People's Hospital of Xinjiang Uygur Autonomous Region

summary: Myocardial fibrosis (MF) represents a major pathological alteration observed in the progression of numerous heart conditions. The presence of excessive myocardial fibrosis is instrumental in the worsening of different heart diseases, which can ultimately lead to heart failure. It has been found that abnormal expression of Pumilio RNA-binding family member 2 (PUM2), an RNA-binding protein, is a contributing factor in the development of a variety of diseases. This study aims to investigate how PUM2 affects the expression and alternative splicing of genes associated with MF in H9C2 cells, thereby elucidating the role of PUM2 in this context.

overall_design: Inhibition of PUM2 expression in H9C2 cardiomyocytes was achieved through siRNA transfection. Cell proliferation was assessed using the Cell Counting Kit-8 (CCK-8)   assay, while apoptosis was detected via flow cytometry. RNA-seq was utilized to analyze the differential gene expression profiles and alternative splicing events in H9C2 cells regulated by PUM2. The sequencing results were confirmed through real-time quantitative polymerase chain reaction (RT-qPCR) experiments.

first: Zilong

first: Hangyu

last: Zhou

first: Wei

last: Zhu

first: Adili

last: Diliyaer

first: Yong

last: Liu

first: Wenzheng

first: Zhao

last: Wang


title: Essential role of NONO-HOXA1-Wnt axis in cardiomyocyte differentiation

status: Public on Dec 29 2025

city: Shanghai

first: Feizhen

last: Wu

state: Shanghai

address: Zhangheng Road 825, Pudong

department: Intelligent Medicine Institute

country: China

institute: Fudan Univ, Shanghai, China

type: Expression profiling by high throughput sequencing

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.

last: Sheng

first: Guoying

last: Huang

first: Zhiyu

last: Feng

first: Yuan

last: Gao


title: Haptoglobin and Hemopexin Redirect Heme-Driven Oxidative Stress and Neurotoxicity in Organotypic Brain Slices

city: Zürich

first: Raphael

middle: Matthias

last: Buzzi

address: Rämistrasse 100

department: Division of Internal Medicine

country: Switzerland

institute: Universitätsspital and University of Zurich

summary: The mechanistic links between hemoglobin oxidation, heme release, and neuronal death after intracerebral hemorrhage are incompletely defined. Using organotypic brain-slice cultures (BSCs) that model the RBC-toxin cascade, we dissect how the scavenger proteins haptoglobin (Hp) and hemopexin (Hpx) interrupt this pathology. BSCs exposed to free hemoglobin, heme, or their complexes (HbHp, hemeHpx) reveal that both Hb and heme drive iron-dependent neuronal injury, while Hp and Hpx confer protection by distinct mechanisms. Multi-modal readouts – including iron quantification, lipid peroxidation, neuronal apoptosis, and RNA-seq – demonstrate that Hpx abolishes toxicity by sequestering heme, whereas Hp stabilizes Hb and enables Nrf2-dependent cytoprotective gene expression. These data quantitatively map how Hp and Hpx reroute hemolytic toxicity toward resilience.

overall_design: RNA-seq profiling of wildtype C57BL/6J organotypic brain slice cultures exposed to free hemoglobin, free heme, or their respective scavenger complexes (haptoglobin for hemoglobin, hemopexin for heme).

first: Anna-Lea

last: Stalder

first: Dominik

middle: J

last: Schaer

middle: M


title: Chemotherapy triggers immune evasion by fostering LEPR+ Kupffer cell differentiation in liver metastases [CUT&Tag, ATAC-seq]

first: Xuege

address: 320 Yueyang Road

institute: Shanghai Institute of Nutrition and Health

type: Genome binding/occupancy profiling by high throughput sequencing

summary: Conventional chemotherapy achieves clinical efficacy beyond its cytotoxic effects by reactivating immune surveillance. However, whether chemotherapy promotes immune evasion by remodeling the tumor microenvironment (TME) remains largely unexplored. Here, we integrate cross-species single-cell and spatial transcriptomics to explore how chemotherapy reprograms immune cell dynamics and plasticity. Our findings reveal a central role for chemotherapy-educated, liver-resident Kupffer cells (KCs) in promoting immune tolerance and chemoresistance in liver metastases. These reprogrammed KCs, characterized by leptin receptor expression (LEPR+), originate from preexisting KCs and are differentiated via STING-ID1 signaling triggered by cGAMP released from chemotherapy-treated tumor cells. Unlike conventional KCs, LEPR+ KCs infiltrate tumors and engage in MerTK-dependent efferocytosis, which diminishes chemotherapy-induced immunogenic cell death (ICD) and suppresses antitumor immunity. Notably, targeting LEPR+ KCs enhances tumor immunogenicity and strengthens antitumor T-cell responses. Our study demonstrates that therapy-induced KC differentiation fosters immune evasion and suggests combining efferocytosis inhibitors with immunotherapy to overcome chemoresistance.

overall_design: This series is under a superseries and composed of cut&tag seq profiles and atac seq profiles.

first: Jun

last: Qin

first: Qiang

last: Pan

first: Yaqi

last: Li


title: Fructose-1,6-Bisphosphate Aldolase B (ALDOB) Regulates Hepatoblastoma Progression through ALDOB-AKT1/2-PPP1CC Complex Formation

city: Qingdao

first: Xiongwei

state: Shandong

address: Jiangsu road

institute: the Affiliated Hospital of Qingdao University

summary: Transcriptomic profiling of pediatric hepatoblastoma tissues revealed significant downregulation of ALDOB, underscoring transcriptome analysis as a key approach to uncover metabolic dysregulation and identify diagnostic biomarkers

overall_design: Transcriptome sequencing of liver tumor and adjacent non-tumor tissues samples from six patients.


title: Pathophysiological Significance of Impaired KAT7-Dependent Histone H3K14 Acetylation During Zinc Deficiency [ChIP-seq_Mice]

city: Tokyo

first: Takao

last: Fujisawa

address: 7-3-1, Hongo, Bunkyo-ku

country: Japan

institute: The University of Tokyo

summary: Zinc is an indispensable micronutrient for optimal physiological functions, and zinc deficiency has been implicated in the pathogenesis of various human diseases. One potential mechanism underlying such pathogenic effects is the alteration of gene expression caused by zinc deficiency; however, the details of this process remain largely unexplored. Here, we show that during zinc deficiency, the histone acetyltransferase KAT7 loses its enzymatic activity, leading to the attenuated acetylation of histone H3 at Lys14 (H3K14ac) at enhancer regions. Physiologically, the decrease in H3K14ac leads to the upregulation of the expression of ZIP10, a plasma membrane-localized zinc transporter, thereby facilitating the import of extracellular zinc to maintain cellular zinc homeostasis. Moreover, prolonged zinc deficiency in mice induced by a zinc-deficient diet or high-fat diet, accompanied by decreased H3K14ac levels in the liver, upregulated the expression of genes associated with intracellular lipid droplet formation, leading to the accumulation of lipids within liver tissue. Our findings demonstrate that cells respond to zinc deficiency by converting it into an epigenetic signal that drives physiological or pathophysiological biological processes.

overall_design: Mice were fed a normal diet or a zinc-deficient diet for two weeks. Then DNA was isolated using SimpleChIP Enzymatic Chromatin IP Kit and subjected to ChIP-seq.

first: Satoshi

last: Takenaka


title: ETC-501 is a Brain Penetrant MNK Kinase Inhibitor that Potentiates TMZ-Induced Senescence and Sensitizes Glioblastoma Cells to Senolytic Therapy

city: Singapore

first: Giselle

last: Nah

address: 8 College Road

country: Singapore

institute: Duke-NUS Medical School

summary: Glioblastoma (GBM) is the deadliest primary brain tumor in adults, with a median survival of only 15 months and fewer than 10% of patients surviving beyond 5 years. Despite aggressive multimodal therapies, including surgical resection, radiation, and temozolomide (TMZ) chemotherapy, recurrence is almost inevitable. The MNK-eIF4E axis plays a significant role in cancer cell survival, and MNK1 and MNK2 are upregulated in gliomas. In this study, we discovered that elevated MNK1/2 expression correlates with poor prognosis and aggressive GBM phenotypes. Development of ETC-501, a selective brain-penetrant MNK kinase inhibitor, enabled modulation of key oncogenic pathways, including MYC signaling, DNA replication, cell cycle regulation, and inflammation. ETC-501 effectively inhibited GBM proliferation, impaired DNA damage repair, delayed cell cycle progression, and suppressed ribosome biogenesis. Notably, in combination with TMZ, ETC-501 not only enhanced senescence but also attenuated the senescence-associated secretory phenotype in GBM cells. The augmented senescence increased the vulnerability of GBM cells to the senolytic agent navitoclax, facilitating targeted elimination of residual senescent cells. These findings underscore the therapeutic potential of MNK inhibition in GBM, offering a promising strategy to advance GBM treatment paradigms and improve patient outcomes.

overall_design:
To assess how the effects of ETC-501 on GBM cells, we treated LN229 and T98G GBM cell lines with 5 µM of ETC-501 for 5 hours.
We then performed gene expression profiling using RNA-seq data from 2 GBM cell lines, each treated with DMSO or ETC-501 at one time point.

first: Yuk Kien

last: Chong

first: Fatin Nasha

last: Salami

first: Kian Leong

last: Lee

first: See Wee

last: Lim

first: Qing You

last: Pang

first: Mengge

last: Yu

first: Zhen Wei

last: Neo

first: Jabed

last: Iqbal

first: Kassoum

last: Nacro

first: Jeffrey

last: Hill

first: Alex

last: Matter

first: Henry

last: Yang

first: Beng Ti

last: Ang

first: Carol

last: Tang

first: S. Tiong

last: Ong


title: 2p Gain-Driven REL Overexpression Confers Resistance to BTK Inhibitors in Chronic Lymphocytic Leukemia

city: Paris

first: Wail

last: Zeitouni

address: 29, rue du Faubourg Saint-Jacques

department: Paris Biotech Santé

country: France

institute: GenoSplice technology

summary: Gain of the short arm of chromosome 2 (2p) is a frequent chromosomal abnormality in advanced Chronic Lymphocytic Leukemia (CLL), but how it contributes to CLL pathogenesis and progression is still poorly understood. Using a multiparameter approach that combines scRNA sequencing, cellular biology on primary CLL cells and engineered cell lines, as well as clinical analyses, our data show that 2p gain leads to NF-kB activation through REL overexpression, thereby contributing to BTKi resistance.

overall_design: single-cell RNA-seq profiling of five peripheral blood mononuclear cells (PBMC) samples from CLL patients with a gain of the short arm of chromosome 2.

first: Lea

last: Dehgane

first: Elise

last: Chapiro

first: Florence

last: Nguyen-Khac

first: Santos

middle: A

last: Susin


title: Transcriptional dynamics of nitrogen fixation and senescence in soybean nodules: A dual perspective on host and Bradyrhizobium regulation

city: Davis

first: Patricia

last: Baldrich Gonzalez

state: CA

address: 451 Health Sciences Dr., Davis, CA 95616

department: Genome Center

country: USA

institute: University of California - Davis

type: Non-coding RNA profiling by high throughput sequencing

summary: The soybean–Bradyrhizobium symbiosis enables symbiotic nitrogen fixation (SNF) within root nodules, reducing reliance on synthetic N fertilizers. However, nitrogen fixation is transient, peaking several weeks after Bradyrhizobium colonization and declining as nodules senesce in coordination with host development. To investigate the regulatory mechanisms governing SNF and senescence, we conducted a temporal transcriptomic analysis of soybean nodules colonized with Bradyrhizobium diazoefficiens USDA110. Weekly nodule samples (2 to 10 weeks postinoculation, wpi) were analyzed using RNA and small RNA sequencing, and acetylene reduction assays assessed nitrogenase activity from 4 to 7 wpi. We identified three major nodule developmental phases: early development (2 to 3 wpi), nitrogen fixation (3 to 8 wpi), and senescence (8 to 10 wpi). Soybean showed extensive transcriptional reprogramming during senescence, whereas Bradyrhizobium underwent major transcriptional shifts early in development before stabilizing during nitrogen fixation. We identified seven soybean genes and several microRNAs as candidate biomarkers of nitrogen fixation, including lipoxygenases (Lox), suggesting roles for oxylipin metabolism. Soy hemoglobin-2 (Hb2), previously classified as nonsymbiotic, was upregulated during senescence, implicating oxidative stress responses within aging nodules. Upregulation of the Bradyrhizobium paa operon and rpoH during senescence suggesting metabolic adaptation for survival beyond symbiosis. Additionally, Bradyrhizobium nif gene expression showed stage-specific regulation, with nifK peaking at 2 wpi, nifD and nifA at 2 and 10 wpi, and nifH, nifW, and nifS at 10 wpi. These findings provide insights into SNF regulation and nodule aging, revealing temporal gene expression patterns that could inform breeding or genetic engineering strategies to enhance nitrogen fixation in soybeans and other legume crops.

overall_design: small RNAseq and RNAseq of Soybean-USDA110 nodules at different stages of development, including three biological replicates of each condition.

first: DelPercio

last: Ryan

first: Meyers

last: Blake

first: Baldrich

last: Patricia


title: Pathophysiological Significance of Impaired KAT7-Dependent Histone H3K14 Acetylation During Zinc Deficiency [ChIP-seq_Hela]

first: Takao

last: Fujisawa

overall_design: HeLa cells were culutred with the indicated medium (zinc-normal or zinc-defieicnt) or treated with each siRNA (non-targeting or KAT7). Then DNA was isolated using SimpleChIP Enzymatic Chromatin IP Kitand subjected to ChIP-seq

first: Satoshi

last: Takenaka


title: Chemotherapy triggers immune evasion by fostering LEPR+ Kupffer cell differentiation in liver metastases [RNA-seq]

first: Xuege

last: Wang

sample_organism:
Homo sapiens
Mus musculus

platform_organism:
Homo sapiens
Mus musculus

overall_design:
This series is under a superseries and composed of mRNA seq profiles, scRNA seq profiles and stereo seq profiles.

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

first: Jun

last: Qin

first: Qiang

last: Pan

first: Yaqi

last: Li


title: LXR agonism enhances T cell activation upon crosspresentation.

city: Berlin

first: Benjamin

middle: N

last: Ostendorf

address: Augustenburger Platz 1

country: Germany

institute: Charité University Medicine

summary: Here, we analyze transcriptional profiles of OT-I CD8+ T cells co-cultured with bone marrow-derived dendritic cells pulsed with the SIINFEKL peptide in the absence of presence of the synthetic LXR agonist RGX-104.

overall_design: Differential gene expression analysis of flow cytometry-sorted OT-I CD8+ T cells after co-culture with bone marrow-derived dendritic cells in the presence of absence of the synthetic LXR agonist RGX-104.


title: Ketogenic diet dampens excitatory neurotransmission by shrinking synaptic vesicle pools

city: Philadelphia

first: Yemin

last: Lan

state: PA

address: 3400 Civic Center Blvd

institute: University of Pennsylvania

summary: The ketogenic diet (KD) is a common dietary intervention for treating seizures in intractable childhood epilepsies and has been proposed to improve disease outcome in neurodegenerative disorders. Despite its clinical applications, we know little about how this diet impacts brain circuitry and neuronal function to elicit its protective effects. Here, we examined the impact of the KD on hippocampal function through integrative analysis of gene expression, epigenetics and neurotransmission.  We found that KD induces profound transcriptional reprogramming of the hippocampus, including altered expression of numerous synaptic genes. Proteomic analysis of histone variants and post-translational modifications also revealed significant changes in activating and repressive epigenetic marks in the hippocampus of KD mice. To determine how transcriptional and epigenetic rewiring of the hippocampus under KD impacts neurotransmission, we performed electrophysiological recordings to examine synaptic dynamics and synaptic summation at CA3-CA1 synapses. We found that KD diminishes synaptic gain and dampens short-term plasticity at excitatory synapses, resulting in reduced summation of synaptic inputs at the circuit level. We determined that the dampening of synaptic gain was due to a reduction in size of the readily releasable as well as the total of synaptic vesicles in excitatory but not inhibitory synapses. Our findings show that the ketogenic diet triggers synaptic remodeling in the hippocampus, driven by broad transcriptional and epigenetic changes that reduce synaptic vesicle pools and short-term plasticity at excitatory synapses ultimately dampening excitatory synaptic gain and integration at the circuit level. These synaptic adaptations may represent a major mechanism underlying the anti-epileptic effects of this diet.

overall_design: ChIP-seq analysis of H3K4me1 histone modifications in the hippocampus of mice fed either a chow or ketogenic diet.

first: Marion

middle: I

last: Stunault

first: Pan-Yue

last: Deng

first: Anjali

last: Yadav

first: Erica

last: Periandri

first: Francisca

last: de Luna Vitorino

first: Michael

last: Thomsen

first: Jasmin

last: Sponagel

first: Amelia

last: Barfield

first: Renzelle

last: Ponce

first: Layla

last: Foroughi

last: Garcia

first: Gabor

last: Egervari

first: Vitaly

last: Klyachko

first: Ghazaleh

last: Ashrafi


title: ICAM1 mRNA Functions Independently of Protein Coding to Inhibit Translation via a dsRNA-ILF2/ILF3 Pathway in Lung Cancer

city: Nanjing

first: siyuan

last: jiang

state: Jiangsu

address: sipailou NO2

department: Zhongda Hospital

institute: Southeast University

summary: This study investigates the role of Intercellular Adhesion Molecule 1 (ICAM1) in lung cancer using RNA-seq and CUT&Tag sequencing. We performed ICAM1 knockout and knockout&knockdown experiments in CALU-1 lung cancer cells to examine changes in gene expression and chromatin accessibility. Our findings provide insights into ICAM1's regulatory mechanisms and its potential as a therapeutic target in lung cancer.

overall_design: RNA-seq was performed on ICAM1 knockout and knockout&knockdown CALU-1 cells, along with control samples. CUT&Tag sequencing was conducted on ICAM1 knockdown in Calu-1 knockout cells and corresponding controls to assess changes in chromatin accessibility.

first: Siyuan

last: Jiang

first: Jinghan

last: Sun

first: Ya

last: Gao

first: Haifeng

last: Zhang

first: Ying

last: He

first: Yibi

first: Zhiyuan

last: Xu

first: Shuwen

last: Cheng

first: Hong

last: Yan

first: Liqiang

last: Duan

first: Peng

first: Qinong

last: Ye

first: Shan


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: Profound effect of asparagine-linked glycosylation protein 11 (TgALG11) on genomic expression of Toxoplasma gondii II

city: Wenzhou

first: Ya-Ni

last: Mou

state: China

address: Chashan University Town, Ouhai District, Wenzhou City, Zhejiang Province

institute: Wenzhou Medical University

summary: Toxoplasma gondii is an intracellular parasite that relies on complex molecular mechanisms to support its proliferation and survival. In this study, we investigate the role of TgALG11 in these processes and explore the underlying regulatory network. Our data demonstrate that TgALG11 is essential for maintaining T. gondii proliferation and for normal N-glycosylation. To further elucidate the molecular mechanisms underlying the essential functions of TgALG11, we performed transcriptome sequencing to identify the genes regulated by this factor. Total RNA was extracted from iTgALG11 strains cultured with 0.5 μg/ml ATc (knockdown strain) and DMSO (control), and subjected to deep sequencing using the Illumina Novaseq™ 6000 platform. The sequence reads were subsequently mapped to the T. gondii genome, resulting in a comprehensive transcriptome encompassing 8,948 genes. Among these, 8549 genes were differentially expressed due to TgALG11 deficiency, including 1307 downregulated and 1951 upregulated genes (DESeq, |log2(FoldChange)| ≥ 1, q ≤ 0.05). Functional enrichment analysis revealed that these genes were associated with various Gene Ontology (GO) terms and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways. Our findings provide novel insights into the profound impact of TgALG11 on the T. gondii transcriptome, underscoring its critical role in parasite biology.

overall_design: Three replicates of iTgALG11 transgenic parasites cultured with 0.5 μg/ml ATc (knockdown strain) and DMSO (control) were prepared and sent to LC Bio Technology CO.,Ltd (Hangzhou, China) for TgALG11-specific transcriptome construction and analysis. .

first: Feng

last: Tan

first: Yani

first: Siyu

last: Tian


title: Pathophysiological Significance of Impaired KAT7-Dependent Histone H3K14 Acetylation During Zinc Deficiency [RNA-seq]

first: Takao

last: Fujisawa

overall_design: Mice were fed a normal diet or a zinc-deficient diet for two weeks. Then RNA was isolated from the liver using ISOGEN and subjected to RNA-seq.

first: Satoshi

last: Takenaka


title: Combination of PARP and KRASG12D Inhibitors Enhances Therapeutic Efficacy by Exploiting Vulnerabilities(scRNA)

city: Beijing

first: Xin

state: Undefined

address: Panjiayuannanli 17

institute: National Cancer Center/Chinese Academy of Medical Sciences (CAMS) and Peking Union Medical College (PUMC)

summary: Combination of PARP and KRAS G12D Inhibitors Enhances Efficacy Therapeutic Vulnerabilities in PDAC

overall_design: For the subcutaneous KPC1199 tumor models, treatment was initiated when tumors reached an average volume of 80–200 mm3. For the treatment group, Olaparib was intraperitoneally injected daily with a dose of 50 mg/kg, and MRTX1133 was intraperitoneally injected daily with a dose of 30 mg/kg.

last: Chen

first: Rongli

first: Min

last: Deng


title: 3D genome organization in tissue regeneration: functional requirement of long-range chromatin loops [RNA-seq]

city: Barcelona

first: Carlos

last: Camilleri-Robles

address: Av. Diagonal

country: Spain

institute: UB

summary: The three-dimensional (3D) organization of the genome plays a fundamental role in gene expression regulation. However, little is known about how transcriptional responses are influenced by changes in genome architecture during tissue regeneration. Here, we used Hi-C to profile 3D chromatin conformation during Drosophila wing imaginal disc regeneration. We found that, although compartments and topologically associating domains (TADs) are largely maintained, regeneration is accompanied by reduced compartmentalization and increased boundary insulation. Notably, we identified three long-range chromatin loops with increased contact frequency during regeneration. Precise deletion of their anchors demonstrated that these loops are essential for proper disc regeneration but dispensable for normal wing development. Furthermore, disruption of any of these loops resulted in convergent changes in both gene expression and H3K4me1 3D environment, suggesting their coordinated activity during regeneration. These findings provide functional evidence that 3D genome architecture actively contributes to the regenerative process.

overall_design: RNA-seq and Hi-C profiling of L3 wing discs in control conditions and after 16 h of rpr expression to induce cell death. For the RNA-seq experiments, mutant samples were compared to control samples that were treated in parallel.

first: Palmira

last: Llorens-Giralt

first: Leo

last: Zuber

first: Jenisha

last: Khadka

first: Maria

last: Marti-Marimon

first: Florenci

last: Serras

middle: C

last: Gambetta

first: Marc

last: Marti-Renom

first: Montserrat

last: Corominas


title: The inflamed cauda epididymidis: a hub for ectopic lymphoid organ genesis

city: Giessen

first: Marek

last: Bartkuhn

state: Hessen

address: Aulweg 132

department: Biomedical Informatics and Systems Medicine

institute: Justus-Liebig-University Giessen

summary: Infection and inflammation of the male reproductive tract are major factors leading to infertility.  Uropathogenic Escherichia coli (UPEC) is a common pathogen specifically affecting the distal parts of the epididymis. The infection causes pathological alterations in the cauda epididymidis and these include interstitial edema, loss of epithelial integrity, leukocyte infiltration within the ducts and the interstitial space, along with fibrosis. A considerable number of patients with epididymitis, even after antibiotic treatment, exhibit the presence of an epididymal infiltrate and suffer from infertility. For this reason, this study focused on investigating the cauda epididymidis at later time points from the infection in a well-established model of acute bacterial epididymitis. We show that multiple elements associated with tertiary lymphoid organs formation, organization and maintenance are present in UPEC-infected epididymidis 28 days post-infection compared to sham cauda epididymidis.

overall_design: Cauda epididymidis from sham and UPEC-infected mice were compared for their differentially expressed genes 28 days post-infection.

first: Monika

last: Fijak

first: Hiba

last: Hasan


title: Combination of PARP and KRAS G12D Inhibitors Enhances Efficacy of Therapeutic Vulnerabilities

last: Xu

summary: To elucidate the molecular basis of the HR deficiency induced by KRASG12D inhibition, we conducted RNA sequencing (RNA-seq) on KRASG12D -mutant PDAC cells (AsPC-1, PANC-1, SW1990) treated with MRTX1133 and KRASG12V -mutant CFPAC-1 cell treated with pan-KRAS inhibitor BI-2865. To futher verified the molecular alternation, we also conducted RNA-seq on KRASG12D-mutant Patient-derived xenograft treated with MRTX1133.

overall_design: For cell lines, AsPC-1, PANC-1, SW1990, and CFPAC-1 cells were cultured in duplicate in 10-cm dishes. The cells were either left untreated or treated with 50 nmol/L MRTX1133(AsPC-1, PANC-1, SW1990) or 100 nmol/L BI-2865 (CFPAC-1). Cells were collected 24 hours after treatment. For tumor tissue,  tumor tissue from mice bearing pancreatic PDX in vehicle group and combination treatment group(Olaparib and MRTX1133) were collected after endpoint.

first: Ming


title: Transcriptomic analyses of mouse livers from an 18-month oral carcinogenicity study of HFPO-DA with a 9-month chronic toxicity phase

city: Asheville

first: Melissa

middle: Marie

last: Heintz

state: NC

address: 31 College Place, Suite B118

institute: ToxStrategies

summary: Transcriptomic anlayses were conducted on liver tissue from male and female CD-1 mice  orally exposed to 0, 0.05, 0.1, 0.5 or 5 mg/kg-bw/day HFPO-DA (ammonium 2,3,3,3-tetrafluoro-2-(heptafluoropropoxy)-propanoate; CASRN 62037-80-3) in a 18-month carcinogencity study that included a 9-month chronic toxicity phase in support of an investigation of the mode of action for HFPO-DA-mediated liver toxicity. This combined chronic toxicity and carcinogenicity study complied with Good Laboratory Practice (GLP) and Organization for Economic Co-operation and Development (OECD) 453 test guidelines for combined chronic toxicity/carcinogenicity studies. Transcriptomic responses in exposed mice were compared to time-matched control mice. Pathway enrichment of differentially expressed genes, as well as benchmark dose modeling and functional classification of dose-responsive genes were conducted. A low hepatic transcriptomic response was observed in mice exposed to 0.05 or 0.1 mg/kg-bw/day HFPO-DA for 9 or 18 months. In mice exposed to 0.5 or 5 mg/kg-bw/day, the top most significantly enriched gene sets were similar in male and female mouse livers regardless of exposure duration. Upregulated gene sets were related to b-oxidation of fatty acids and fatty acid metabolism, PPAR signaling, and peroxisome signaling. Downregulated gene sets were related to innate immune responses and amino acid metabolism. Results from benchmark dose-response analysis indicate livers from male mice exposed to HFPO-DA for 9 months had the greatest transcriptomic response.

overall_design: Comparative gene expression profiling analysis of RNA-seq data from FFPE liver tissue of male and female CD1 mice orally exposed to 0, 0.05, 0.1, 0.5 or 5 mg/kg-bw/day HFPO-DA (n= 3-5 per treatment group) once daily for a total of 9 or 18 months.

first: William

middle: D

last: Klaren

first: Amanda

last: Buerger

first: Chad

last: Thompson

first: Laurie

last: Haws


title: Sustained STING-IRF7 signaling aggravates LPS-induced endometrial inflammation via excessive neutrophil extracellular traps generation

status: Public on Dec 27 2025

city: Yantai

first: Min

last: Chu

address: No. 20 Yuhuangding Estern Road

institute: Yantai Yuhuangding Hospital

summary: The stimulator of interferon genes (STING) is a central mediator of innate immune sensing and represents a critical regulator of chronic inflammation. Upon persistent infection, excessive neutrophil activation leads to the formation of neutrophil extracellular traps (NETs) that damage the tissues. However, the mechanism by which STING signaling regulates NETs formation under chronic inflammatory conditions remains poorly understood. In this study, using LPS-induced murine endometritis models in wild-type and STING-deficient mice, we demonstrated that STING deficiency significantly suppressed myeloperoxidase activity, and diminished NETs formation. We identified neutrophil surface molecular CD11b as a key downstream target of STING, whose expression was transcriptionally regulated via IRF7. Furthermore, the STING-IRF7 axis was found to drive lipocalin-2 (LCN2) expression, which acted through its receptor MC4R to upregulate intracellular adhesion molecule-1 (ICAM-1), thereby facilitating neutrophil recruitment and NETosis during LPS stimulation. The role of this pathway was validated both in vitro using isolated neutrophils and in vivo using Lcn2-/- mice. Moreover, STING deficiency reprogramed the endometrial immune microenvironment by reducing inflammatory infiltration and restoring receptivity transcription factor homeobox A10 (HOXA10). Our findings revealed a novel mechanism in which the STING-IRF7 pathway exacerbated endometrial inflammation and tissue damage by coordinately upregulating CD11b and activating the LCN2-ICAM-1 axis. Consequently, targeting the STING signaling pathway may offer a promising therapeutic strategy for chronic endometritis.

overall_design: For LPS-induced endometritis, uterine tissues were collected from two groups: LPS-treated STING-deficient mice and LPS-treated WT mice. Each group included three biological replicates to ensure statistical robustness. In this study, using LPS-induced murine endometritis models in wild-type and STING-deficient mice, we demonstrated that STING deficiency significantly suppressed myeloperoxidase activity, and diminished NETs formation.

first: Ding

last: Ma

first: Zhan

last: Song

first: Li

last: Liang

first: Fengjuan

last: Xing

first: Hongchu

last: Bao


title: Gravitational and mechanical forces shape mitochondrial translation

city: Wako city

first: Taisei

last: Wakigawa

state: Saitama prefecture

address: 2-1, Hirosawa

institute: RIKEN

summary: Life on Earth has evolved in a form suitable for the gravitational force of 1 × g. Although the pivotal role of gravity in gene expression has been revealed by multiomics approaches in space-flown samples and astronauts, the molecular details of how mammalian cells harness gravity have remained unclear. Here, we show that mitochondria utilize gravity to activate protein synthesis within the organelle. Genome-wide ribosome profiling unveiled reduced mitochondrial translation in mammalian cells and Caenorhabditis elegans under microgravity in the International Space Station and under simulated microgravity in the 3D-clinostat on the ground. In addition, we found that cell adhesion through laminin–integrin interaction, which is attenuated by microgravity, and the downstream FAK, RAC1, PAK1, BAD, and Bcl-2 family proteins relay the signals for mitochondrial protein synthesis. Consistent with the role of integrin as a mechanosensor, we observed the decrease in mitochondrial translation by minimization of mechanical stress in mouse skeletal muscle. Our work provides mechanistic insights into how cells convert gravitational and mechanical forces into translation in an energy-producing organelle.

sample_organism:
Caenorhabditis elegans
Homo sapiens
Mus musculus

overall_design: Ribosome profiling; RNA-Seq; MitoIP-Thor-Ribo-Seq

first: Yusuke

last: Kimura

first: Mari

last: Mito

first: Toshiya

last: Tsubaki

first: Hironori

last: Saito

first: Abdul

middle: H

last: Khan

first: Tohru

last: Yamamori

first: Tomokazu

last: Yamazaki

first: Akira

last: Higashibata

first: Tatsuhisa

last: Tsuboi

first: Taku

first: Atsushi

last: Higashitani

first: Yuichi

last: Shichino

first: Shintaro

last: Iwasaki


title: LXR agonism promotes T cell effector chromatin landscapes upon crosspriming by dendritic cells.

first: Benjamin

last: Ostendorf

summary: Here, we assess chromatin accessibility profiles of OT-I CD8+ T cells upon co-culture with antigen-pulsed BMDCs in the presence or absence of the synthetic LXR agonist RGX-104.

overall_design: ATAC-seq of OT-I CD8+ T cells after co-culture with BMDCs in absence or presence of a synthetic LXR agonist.


title: Transcriptional profiles of tumor-draining lymph node resident CD11c+ cells in wildtype versus APOE-KO mice

summary: Here, we analyze transcriptional profiles of CD11c+ enriched cells from the lymph nodes draining E0771-cOC tumors in either wildtype or APOE-KO mice.

overall_design: Differential gene expression between CD11c+ cells from APOE-KO versus wildtype mice.


title: Epigenetic Signatures of Brain Aging by Single Nucleus Methylation Sequencing [FC-9mo-m]

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: Illustrating aging effects on the epigenomic features of brain is critical to understand brain functional decline and neurodegeneration. Single nucleus methylation sequencing was applied to brain regions of both male and female mouse at the age of 2, 9 and 18 months. We use these data to identify the epigenomic changes with aging in mouse brains.

overall_design: Apply snmC-seq3 to mouse brain regions to identify aging effects on epigenomics

first: Wei

last: Tian

first: Anna

last: Bartlett

first: Jordan

last: Altshul

first: Rosa

last: Gomez Castanon

last: Nery

first: Jacinta

last: Lucero

first: Julia

middle: K

last: Osteen

first: Huaming

last: Chen

first: M

last: Behrens


title: Kinetical scRNAseq Analysis Reveals Immune Mechanisms Underlying Hindered Lung Recovery following Influenza Virus Infection in Aged Hosts

city: Charlottesville

first: Jie

last: Sun

state: VA

address: 345 Crispell Dr

department: Beirne B. Carter Center for Immunology Research

institute: University of Virginia

summary: Aging is a major risk factor for host morbidity and mortality upon acute respiratory virus infections. To better elucidate the immune determinants of viral pathogenesis during aging, we conducted a time-course single-cell RNA sequencing (scRNAseq) and high-dimensional flow cytometry analysis on the pulmonary responses against influenza infection in young or aged mice. Notably, aged mice exhibited decreased populations of alveolar macrophages (AMs) and dendritic cells (DCs), alongside an increase in monocyte-derived macrophages (MoMs) and interstitial macrophages (IMs), which last weeks after acute viral infection. Additionally, there was enhanced accumulation of respiratory adaptive immune cell cells including tissue resident helper CD4 T cells (TRHs), CD8 tissue resident memory cells (TRMs) and a unique B cell population resembling age-associated B cells. Gene set enrichment analysis (GSEA) comparing lung transcriptomes of young and aged mice across time points highlighted persistent type I and type interferon signaling in aged hosts, especially in the macrophage population. Interestingly, inhibiting interferon signaling in aged mice after viral clearance led to ameliorated long-term sequelae, along with a decrease in IM and TRH populations. Our findings suggest that IFNα/γ signaling, particularly in MoM/IM, is pivotal in the development of long-term sequelae following acute respiratory infections in aged hosts.

overall_design: To distinguish tissue resident and circulating/vasculature-associated immune population, 2μg/ms anti-mouse biotin conjugated CD45 antibody (Biolegend, Clone: 30-F11) was injected intravascularly 5min before humanely euthanizing the animal. Single cell suspention from lung homogenate was stained with DNA-oligo conjugated streptavidin. Single Cell 5’ Library & Gel Bead Kit with Feature Barcoding was then utilized for scRNAseq library construction.

first: Yue

last: Wu


title: Gene regulatory programs underlying diversification of facial ligaments and tendons in zebrafish

city: Los Angeles

first: Gage

last: Crump

address: 1425 San Pablo St.

department: Stem Cell

institute: USC

summary: The musculoskeletal complex is held together by ligaments connecting skeletal elements and tendons bridging the musculature with the skeleton. How connective tissues of the right type and function are specified in distinct regions of the developing body remains understudied. To understand the gene regulatory programs specifying connective tissue subtypes, we generated single-cell datasets of RNA expression and chromatin accessibility for scxa:mCherry+ connective tissue cells of the developing zebrafish face. We identified cell clusters corresponding to tendon, ligament, periligament, perichondrium, and other connective tissue types, which we validated by in situ hybridization. We also uncovered tendon and ligament cells sharing an osteogenic signature, which may explain the remodeling of ligament-bone interfaces and the formation of sesamoid bone from tendons. This osteogenic potential of tendon and ligament cells is further reflected by co-enrichment of transcription factor-binding motifs for Scx and the osteogenic factor Runx2 in their enhancers. Moreover, several enhancers drive spatially-restricted transgenic activity in distinct ligaments, periligament tissue, perichondrium, and other jaw mesenchyme types, which we used to express a photoconvertible nlsEOS protein and reveal posterior-directed growth of the major jaw-stabilizing ligament. At the anterior end of this same ligament, we show that Nkx3.2 is required for its attachment to the jaw joint. Our study reveals gene regulatory programs for jaw connective tissue diversification and provides a mechanism underlying the propensity of tendons and ligaments to ossify in normal and pathological contexts.

overall_design: Tg(scxa:mCherry)+ single cells or nuclei were extracted and sorted from 5 and 14dpf zebrafish embryos. ScRNA, snRNA, and snATAC libraries were prepared using the 10X Genomics platform.

first: Ryan

last: Roberts

first: Hung-Jhen

first: Kuo-Chang

last: Tseng

first: J

last: Gage Crump


title: Dopamine biosynthesis in plants

city: Berkeley

first: Yezhang

last: Ding

address: 1 Cyclotron Road

institute: Berkeley Lab

summary: Dopamine, an essential human neurotransmitter, also plays important roles in plant-microbe interactions and abiotic stress tolerance in plants. Although dopamine biosynthesis is well-characterized in humans, it remains largely unclear in plants. Through metabolite-based genome-wide association studies, we identified a dopamine biosynthetic gene cluster in Brachypodium distachyon comprising two tyrosine decarboxylase genes and three putative polyphenol oxidase genes. Biochemical and knockout mutant analyses revealed that dopamine biosynthesis proceeds primarily via tyramine as an intermediate, and dopamine oxidation leads to tissue browning in B. distachyon. Homolog searches and enzymatic assays suggest that the dopamine biosynthetic pathway is likely conserved across numerous plant species. This discovery provides valuable insights into plant dopamine biosynthesis with potential applications in reducing food browning, improving plant stress resilience, and bioengineering valuable compounds.

overall_design: RNAseq profiling of 2- and 4-week-old Brachypodium distachyon Bd21-3 roots and shoots. These plants were grown in a hydroponic system.

first: John

last: Vogel

first: Trent

last: Northen


title: Vincristine induces spermatogenic impairment in a B-ALL PDX mouse model via downregulation of Tssk4 and Ccdc159: RNA-seq transcriptomic profiling

status: Public on Dec 26 2025

city: Fuzhou

first: Meng

last: Fu

state: Fujian

address: 310 Yangqiao Middle Road

institute: Fujian Children's Hospital

summary: This dataset contains RNA sequencing (RNA-seq) data generated from testicular tissues of a B-cell acute lymphoblastic leukemia (B-ALL) patient-derived xenograft (PDX) mouse model treated with vincristine (VCR). The study aimed to elucidate the molecular mechanisms underlying VCR-induced reproductive toxicity. Samples were collected from multiple experimental groups, including normal controls (NC), leukemia-bearing controls (ALL), and VCR-treated groups with varying leukemia infiltration levels. Transcriptomic analysis revealed widespread gene expression perturbations following VCR exposure, with significant downregulation of genes crucial for spermatogenesis and sperm flagellar assembly. This data provides a comprehensive resource for understanding the genetic pathways affected by VCR in the testicular microenvironment.

overall_design: RNA-seq profiling of testicular tissues from five experimental groups of PDX mice: Normal control (NC), B-ALL model control (ALL), VCR-only treated, and VCR-treated with low (Low-VCR) and high (High-VCR) peripheral blood leukemia infiltration.

first: Chaoming

last: Zhou

first: Suyun

first: Shengqi

last: Zheng

first: Xu

last: Cui


title: Chip-seq data for FGFR3-driven gene regulatory network analysis reveals a pro-tumoral role for p63 in luminal bladder tumors.

city: Gif-sur-Yvette

first: Lilia

last: Estrada Virrueta

address: 1, Avenue de la Terrasse

summary: FGFR3 (Fibroblast Growth Factor Receptor 3) is one of the most frequently altered genes in bladder cancer, primarily through activating mutations that drive oncogenesis and are enriched in luminal tumors. However, the underlying gene regulatory network (GRN) remains poorly characterized. Here, we inferred an FGFR3-mutated GRN using a bottom-up bioinformatics approach, integrating transcriptomic data from bladder cancer cell lines, FGFR3-mutated tumors, and FGFR3-perturbation experiments in human and mouse models. Using CRISPR-Cas9 screen public data, we identified transcription factors (TFs) from this GRN that regulate the viability of FGFR3-mutated cells, with a focus on p63 (TP63). We showed that FGFR3 activation upregulates p63 in patient-derived xenografts and cell lines, while single-cell RNA sequencing revealed heterogeneous p63 activation associated with basal differentiation. Functional studies, including TP63 knock-down in FGFR3-dependent in vitro and in vivo models and RNA-seq along with p63 ChIP-seq, demonstrated that p63 directly promotes cell proliferation and migration, and uncovered a positive feedback loop between FGFR3 and p63. Together, these findings identified p63 as a pro-tumorigenic regulator in FGFR3 mutated tumors despite their luminal differentiation and provide a detailed FGFR3-driven GRN, offering insights into FGFR3-induced oncogenic dependency and potential strategies to circumvent resistance to FGFR inhibitors.

overall_design: ChIP-seq of p63 in human bladder cancer cell lines (MGHU3, RT112, VMCUB1).

first: Isabelle

last: Bernard-Pierrot

first: Xiang-Yu

last: Meng

last: Estrada-Virrueta

first: Guerric

last: Gilbert

first: Helene

last: Neyret-Kahn


title: Investigating the Therapeutic Potential of the Antioxidant Epigallocatechin Gallate in Fetal Alcohol Spectrum Disorders: Cognition and RNASeq

first: Anna

last: Ramos-Triguero

address: C/ del Rosselló, 149

institute: FRCB-IDIBAPS

summary: Prenatal alcohol exposure (PAE) impacts fetal development, leading to Fetal Alcohol Spectrum Disorders (FASD) characterized by cognitive, behavioral, and physical impairments. This study explores Epigallocatechin Gallate (EGCG), a potent antioxidant and modulator of neuronal plasticity, as a therapeutic intervention for FASD improvement. In a 12-month pilot study, patients with 40 FASD received 9 mg/kg/day of EGCG, with outcomes assessed through RNA sequencing of blood samples and neurocognitive evaluations (WISC-IV, CBCL 6-18, and NEPSY-II). Reduced levels of oxidative stress were observed after 6 months of daily treatment with EGCG, to maintain the bioavailability of the molecule in the body, with decreased levels of MDA and 8-isoprostane and increased activity of LDH. Significant neurocognitive improvements were shown after one year of treatment in Perceptual Reasoning Index (PRI) and Working Memory Index (WMI) using the WISC-IV test. CBCL test revealed an improvement in aggressive behavior scores after EGCG treatment. NEPSY-II assessment showed improvements in face memory, and delayed face memory. Interestingly, no significant improvements were observed in intelligence quotient, attention, anxiety, or depression, which affect a proportion of individuals diagnosed with FASD. Additionally, EGCG modulates molecular pathways associated with neuroinflammation, oxidative stress, immune response, and neurogenesis. This study highlights EGCG as a potential therapeutic candidate to ameliorate cognitive and behavioral deficits caused by PAE in children affected by FASD, revealing potential pathways and biomarkers that contribute to these improvements. These advancements ultimately aim to enhance the quality of life for FASD patients and their families.

overall_design: RNA-seq analysis was conducted in 8 FASD patients at baseline (t0) and following 12 months of EGCG treatment (t12)

first: Marta

last: Astals-Vizcaino

first: Elisabet

last: Navarro-Tapia

first: Melina

last: Vieiros

first: Adriana

last: Bastons-Compta

first: Leopoldo

last: Martínez

first: Vicente

last: Andreu-Fernández

first: Óscar

last: García-Algar


title: 3D genome organization in tissue regeneration: functional requirement of long-range chromatin loops [Hi-C]

first: Carlos

last: Camilleri-Robles

first: Palmira

last: Llorens-Giralt

first: Leo

last: Zuber

first: Jenisha

last: Khadka

first: Maria

last: Marti-Marimon

first: Florenci

last: Serras

last: Gambetta

first: Marc

last: Marti-Renom

first: Montserrat

last: Corominas


title: VGSC mutations and P450 overexpression are associated with beta-cypermethrin resistance in Aphis gossypii Glover from a Chinese wolfberry (Lycium barbarum L.) field

city: Haikou

first: Yunfei

last: Zhang

address: 58 Renmin Avenue

institute: School of Tropical Agriculture and Forestry, Hainan University

summary: Identification and characterization of genes and target-site mutations associated with beta-cypermethrin resistance in Aphis gossypii Glover collected from a Chinese wolfberry (Lycium barbarum L.) field. we collected a beta-cypermethrin resistant A. gossypii strain (HSP) from a Chinese wolf-berry orchard in a major growing area of Ningxia wolfberry (Wuzhong city). Subsequently, to elucidate the potential roles of P450s, CarEs and GSTs in beta-cypermethrin resistance in the A. gossypii strain, we performed synergistic bioassays, as well as enzyme activity assays, to confirm their effects. Further, we carried out a comparative transcriptome anal-ysis to identified the overexpression of detoxification enzyme genes associated with the beta-cypermethrin resistance. According to the transcriptome variations, we also meas-ured the expression levels of the upregulated P450s genes involved in beta-cypermethrin resistance in the A. gossypii resistant strain, using a quantitative real-time PCR assay. Moreover, the potential mutations in VGSC genes and their frequencies were detected to reveal the VGSC genotype of the resistant strain.

overall_design: A highly beta-cypermethrin-resistant Aphis gossypii population was found in the field while high-throughput RNA-seq was used to determine the transcriptome profile of beta-cypermethrin-resistant (RGL) and beta-cypermethrin-sensitive (SGL) A. gossypii without exposure to beta-cypermethrin. Library construction and sequencing were conducted with three replicates for each pooled strain individuals. The cDNA library sequencing was performed by an Illumina HiSeq 2500 sequencing platform generating paired-end reads.

first: Fang

last: Wang

first: Shujing


title: The impact of Influenza A Virus infection on m6A RNA in MDCK cells

city: Tianjin

first: Shu-Lin

last: Liu

address: No.94 of Weijin Road

institute: Nankai University

summary: m6A is the most common RNA modification in eukaryotic cells. Spatially ordered molecular interactions associated with m6A modification are crucial for the spatial organization and functional distribution in living cells. Our m6A proximity labeling technique utilizes a fusion protein containing the YTH domain to identify m6A sites in host cells before and after viral infection. The m6A-modified RNA is pulled down and subjected to high-throughput RNA sequencing. The results indicate that after infection with Influenza A Virus, the m6A modification levels of ribosome-associated mRNA in host cells are upregulated. By combining downstream molecular biology techniques, we have determined that the upregulation of m6A levels in ribosome-associated mRNA is a key factor in promoting viral infection of cells, which is of significant importance for the synthesis of Influenza A Virus proteins.

overall_design: In MDCK cells, a fusion protein YTH-APEX2 containing the YTH domain was transfected for expression. The control group received no further treatment, while the experimental group was infected with the virus for 24 hours. Subsequently, m6A-modified RNA was pulled down using an antibody against the tag on the fusion protein for high-throughput sequencing analysis.

first: Zhong-Da

last: He

first: Shu-Liu


title: Single embryo total RNA sequencing to map the effect of maternal SETDB1 on the 2-celll and 8-cell transcriptome

city: Grand Rapids

first: Piroska

last: Szabó

state: MI

address: 333 Bostwick Ave NE

department: Department of Epigenetics

institute: Van Andel Insitute

summary: Embryos with maternal mutation of the H3K9 methyltransferase SETDB1 die before implantation. We tested the role of maternal SETDB1 in the timely processes of the preimplantation stage embryo. Using single embryo total RNA sequencing from 2-cell and 8-cell embryos, we found that maternal SETDB1 is required for switching off maternal transcripts by the 2-cell stage, minor ZGA transcripts by the 2-cell stage, and major ZGA transcripts by the 8-cell stage. By timely extinguishing of endogenous retroviruses, oocyte-specific ERVL-MaLRs, many oocyte-specific genes, MERVLs, MERVL LTR-driven chimeric transcripts and ZGA genes as well as KRAB ZF genes, maternal SETDB1 secures the proper transition from totipotency to pluripotency.

overall_design: Setdb1 maternal mutant (Zp3Cre +) and control (Zp3Cre -) 2c and 8c stage mouse embryos were collected at 1.5 dpc and 2.5 dpc, respectively. Single embryo total RNA-seq was done using biological replicates.

middle: E

first: Tie-Bo

last: Zeng

first: Zhen

last: Fu


title: Pancreatic volume and immunological biomarkers predict checkpoint inhibitor-associated autoimmune diabetes in humans.

city: Westmead

first: Christopher

last: Liddle

state: NSW

address: 176 Hawkesbury Rd

department: Westmead Institute for Medical Research

country: Australia

institute: University of Sydney

summary: Background: Checkpoint inhibitor-associated autoimmune diabetes (CIADM) is a rare but life-altering complication of immune checkpoint inhibitor (ICI) therapy. Biomarkers that predict type 1 diabetes (T1D) are unreliable for CIADM. Aim To identify biomarkers for prediction of CIADM. Methods: From our prospective biobank, 14 CIADM patients who had metastatic melanoma treated with anti-PD-1±anti CTLA4 were identified. Controls were selected from the same biobank, matched 2:1. Pre-treatment, on-ICI and post-CIADM serum and peripheral blood mononuclear cells (PBMCs) were analysed. Serum was analysed for T1D autoantibodies, C-peptide, glucose and cytokines. PBMCs were profiled using flow cytometry. Pancreatic volume was measured using CT volumetry. Results: Before treatment, CIADM patients had smaller pancreatic volume (27% reduction, p=0.044) and higher anti-GAD antibody titres (median 2.9 versus 0, p=0.01). They had significantly higher baseline proportions of Th17 helper cells (p=0.03), higher CD4+ central memory cells (p=0.04) and lower naïve CD4+ cells (p=0.01). With ICI treatment, greater declines in pancreatic volume were seen in CIADM patients (p<0.0001). Activated CD4+ subsets increased significantly in CIADM and controls with immune-related adverse effects (IRAE) but not controls without IRAE. Using only pre-treatment results, pancreatic volume, anti-GAD antibody titre and baseline immune flow profile were highly predictive of CIADM development, with an area under the curve (AUC) of >0.96. Conclusions: People who develop CIADM are immunologically predisposed and have antecedent pancreatic and immunological changes that accurately predict disease with excellent sensitivity. These biomarkers could be used to guide ICI use, particularly when planning treatment for low-risk tumours.

overall_design: Fourteen deidentified patients with checkpoint inhibitor (CI)-associated autoimmune diabetes (CIADM) and 28 deidentified treated controls that had longitudinal biospecimens were identified from the prospectively collected Melanoma Institute of Australia medical record database and biospecimen bank.The diagnosis of CIADM was based on new onset diabetes (HbA1c ≥ 6.5% and/or blood glucose ≥ 11mmol/L) in the setting of CI therapy, with evidence of insulin deficiency (either presence of diabetic ketoacidosis or low C-peptide ≤ 0.4nmol/L with elevated glucose). No patients had previous diabetes. Two controls were selected for each CIADM patient, matched as closely as possibly for age (±5 years), gender, type of immune checkpoint inhibitor therapy (single agent anti-PD1 versus combined anti-CTLA4 plus anti-PD1), time on therapy, treatment response and concurrent other immune related adverse effects. Control patients had prospectively collected pre-CI and on-CI FACS sorted CD8 positive periperal blood mononuclear cells (PBMCs) (~3 months after treatment initiation) samples analysed by RNA-seq. CIADM patients similarly had pre-CI and on-treatment PBMCs collected at approximately 3 months. CIADM patients additionally had samples collected approximately 3 months after CIADM diagnosis. Note: for RNA-seq some timepoints have one control case where the second had poor sequence quality.

first: Linda

last: Wu

first: John

last: Wentworth

first: Nicole

last: Fewings

first: Matteo

last: Carlino

first: David

last: Brown

first: Roderick

last: Clifton-Bligh

first: Georgina

middle: V

last: Long

first: Richard

last: Scolyer

first: Norris

last: Nicholas

first: Sarah

last: Sasson

first: Vanessa

last: Tsang

first: Alexander

last: Menzies

first: Jenny

last: Gunton


title: Effect of Low-dose-rate Radiation on Cognition and Gene Expression Profiles in Type II Diabetes Mellitus Mouse Model

city: Seoul

first: Yeonghoon

last: Son

address: 75, Nowon-ro

country: South Korea

institute: Korea Institute of Radiological & Medical Sciences (KIRAMS)

summary: By using RNA sequencing (RNA-seq), we analyzed gene expression profiles in the hippocampus to demonstrate the molecular mechanisms of low-dose-rate radiation in mice model of type II diabetes mellitus

overall_design: Comparative gene expression profiling analysis of RNA-seq data in hippocampus of mice brain following low-dose-rate radiation

first: Yoonsoo

last: Choi

first: YeJi

last: Jeong

first: Soo-Ho

last: Lee

first: Chang Geun

first: Joong-Sun

last: Kim

first: Hae-June


title: Chromatin Assembly Factor 1 is Required for Normal Gene Repression and Facultative Heterochromatin Formation in Neurospora crassa [RNA-seq]

city: Athens

first: Zachary

last: Lewis

state: GA

address: 120 E. Green St.

department: Microbiology

institute: University of Georiga

summary: Formation of facultative heterochromatin by Polycomb Repressive Complex 2 (PRC2) is a well conserved epigenetic mechanism that functions to control transcriptional dynamics across eukaryotes. PRC2 catalyzes histone H3 lysine 27 tri-methylation (H3K27me3), a histone post-translational modification that helps maintain stable gene repression. Gene repression by PRC2 is important for organismal development and defects in PRC2 function are associated with human ailments, such as Weaver syndrome and various cancers. In this study, we reveal the replication-dependent histone chaperone, Chromatin Assembly Factor 1 (CAF-1), is required for normal facultative heterochromatin formation in model fungus N. crassa. CAF-1 deficiency results in widespread misregulation of gene expression, particularly within facultative heterochromatin domains, which is accompanied by a rearrangement of H3K27me3 patterns. Regional losses of H3K27me3 are associated with reduced levels of ASH-1 catalyzed H3K36 methylation, and gains of histone modifications associated with active transcription. Furthermore, analysis of a double mutant deficient for both CAF-1 and PRC2 activity revealed that these complexes play distinct roles in maintaining gene repression and facultative heterochromatin. Collectively, these results shed light on CAF-1's role in maintaining a repressive chromatin environment.

overall_design: RNA-seq performed on mycelial tissue after overnight growth in WT and mutant strains

first: Eduardo

last: Torres

first: Collin

last: Link

first: Rochelle

last: Yap

first: Aileen

last: Ferraro

first: Abigail

last: Deaven

first: Jackie

middle: F

last: Pelham


title: Distinct Physiological and Transcriptomic Responses between Tolerant and Susceptible Rapeseed (Brassica napus) Germplasm to Submergence Stress

city: Yangling

first: Chengyu

last: Yu

state: Shaanxi

address: 3 Taicheng Road

department: College of Agronomy

institute: Northwest A&F University

summary: Waterlogging and submergence are major abiotic stresses impairing rapeseed development and hence evaluation of waterlogging tolerance ability is crucial for the development of tolerant lines through breeding approaches. This study investigated submergence impact on the survival rate, physiological responses, and transcriptomic variation of the young seedlings of 706 Brassica napus germplasm. We identified 57 highly tolerant and 109 highly susceptible accessions underwent six days submergence. Most accessions originated from the downstream of Yangtze River region had higher tolerance level. SOD enzymic activity increased both in the five representative tolerant and susceptible genotypes under submergence stress. POD activity also increased in the tolerant genotypes whereas CAT activity decreased, showing a opposite trend compared to the susceptible genotypes. The tolerant genotypes showed less chlorosis and produced less malondialdehyde than that in the susceptible group, while soluble protein content increased more than that in the susceptible genotypes. Transcriptome analysis detected 5,072 and 5,063 up-regulated genes, as well as 3,512 and 3,889 down-regulated genes in the tolerant / susceptible group in comparison to their respective control. Many genes encoding the transcription factors in AP2/ERF, bHLH, MYB, WRKY, and NAC families were also significantly regulated. The differentially expressed genes shared by the two pairs comparison were mainly enriched in such KEGG pathways as circadian rhythm, tryptophan metabolism, and porphyrin and chlorophyll metabolism. The specific pathways in the tolerant group were enriched in carbon metabolism, phenylpropanoid biosynthesis, and biosynthesis of amino acid etc. while the specific pathways in the susceptible group were more distributed in hormone signal transduction, sucrose and starch metabolism, and vitamin B6 metabolism etc. The results uncovered distinct physiological and transcriptomic differences between tolerant and susceptible genotypes.

overall_design: The young seedlings of five resistant and five sensitive germplasm were divided into two groups: the control group cultivated under normal conditions and the treatment group submerged in water for 24 hours. Then equal amounts of young seedlings of each genotype were mixed for RNA extraction, with three biological replicates for each sample.

first: Xing

last: Su

first: Ronghao

last: Guo

first: Yongli

last: Fu


title: β-sitosterol-mediated cardioprotection: a transcriptomic perspective

city: Xiamen

first: Zhonggui

last: Shan

address: No. 55, Zhenhai Road

department: School of Medicine

institute: Xiamen University

summary: β-sitosterol has been implicated in mitigating cardiovascular diseases, yet its role in MI remains underexplored. This study investigates the therapeutic potential and underlying mechanisms of β-sitosterol  in MI using both in vivo and in vitro models.Transcriptome sequencing combined with molecular docking and protein validation assays revealed that β-SITO exerts its beneficial effects primarily through the regulation of inflammatory and necroptotic signaling pathways, particularly via modulation of NF-κB, NLRP3 inflammasome, and RIPK3/MLKL-mediated necroptosis.

overall_design: RNA-seq analysis of HO-induced NMCMs treated with either vehicle or β-SITO.


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

city: Honolulu

first: Xue

last: Wang

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: Reduced cortico-muscular output   is associated with intrinsic hypoexcitability and reduced persistent inward currents  in motor cortex neurons of TDP-43Q331K ALS mice.

city: Columbia

first: Jose

last: Viteri

state: MO

address: 1030 Hitt St

institute: University of Missouri - Columbia

summary: Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by spinal and cortical motor neuron loss and progressive neuromuscular decline. When ALS pathology involves the primary motor cortex (PMC), cortical excitability is often disrupted, yet how these alterations map onto motor deficits during symptomatic ALS remains unclear. To investigate this, we examined the neuromuscular function, cortico-muscular output, and neuronal excitability of symptomatic 4-month-old TDP-43Q331K mice. TDP-43 mice exhibited reduced neuromuscular excitability and impaired strength compared to WT mice. Cranial motor evoked potentials were significantly reduced in TDP-43 mice, indicating decreased cortical output to muscle. Compared to WT mice, whole-cell patch-clamp recordings from TDP-43 PMC layer V pyramidal neurons revealed intrinsic hypoexcitability, diminished persistent inward currents (PICs), and decreased excitatory synaptic activity. Corroborating PIC findings, immunohistochemical analysis showed reduced colocalization of the PIC-associated proteins Nav1.6 and 5-HT2C with PMC layer V neurons. Bulk RNA-seq of the cortex showed distinct transcriptional profiles in TDP-43 mice, with enrichment analysis indicating altered pathways relating to ion transport, synaptic signaling, and neuronal excitability. These results suggest that cortex-wide transcriptional changes may reflect broader and additional molecular mechanisms underlying cortical hypoexcitability in ALS. Together, our results demonstrate that symptomatic TDP-43Q331K mice exhibit a reduction in cortico-muscular output and PMC neuron excitability, accompanied by reduced PICs and PIC-associated proteins within these neurons. These findings identify cortical hypoexcitability as a defining feature of the TDP-43Q331k ALS mouse model and establish multi-level associations between cortical cellular-level dysfunction and impaired motor systems output.

overall_design: Bulk RNA-seq of brain cortex from c57bl6/n and TDP-43-Q331K (ALS) mice to assess whole tissue transcripomic changes during disease.

first: Nathan

last: Kerr

first: Charles

last: Brennan

first: Priyanka

last: Paradkar

first: Leena

last: Suleiman

last: Wendt

first: Chunhui

last: Xu

first: Hong

last: An

first: Meifang

first: Hiroshi

last: Nishimune

first: Joseph

last: Santin

first: William

last: Arnold


title: Targeting cathepsin B alleviates activation of IL-17A-netrophils axis to suppress atopic dermatitis

city: Nanjing

first: po

last: hu

state: jiangsu

address: 栖霞区 南京中医药大学 B3-F106（栖霞仙林校区）

institute: 南京中医药大学

summary: Atopic dermatitis (AD) is a common chronic relapsing inflammatory skin disease lacking therapeutic drugs that address its complex, heterogeneous pathogenesis. By clinical data analysis and AD model verification, our study demonstrated that lysosomal destabilization and the subsequent cytoplasmic release of cathepsins was a critical pathway that amplifies the Interleukin-17A (IL-17A) inflammatory response and promotes AD progression. We revealed that Isoliensinine (IsoL) is a novel therapeutic agent that can target cathepsin B (CTSB) to delay the progression of AD, rather than alleviate symptoms of inflammation. Mechanistically, IsoL significantly suppressed AD and inhibited inflammation, specifically downregulating IL-17A signaling by suppressing dendritic cell mediated Type 17 T-helper cell (Th17) differentiation, thus suppressing neutrophil infiltration. Rescue experiments confirmed that IsoL’s anti-inflammatory and AD-suppressing effects were dependent on its inhibition of CTSB-IL-17A-neutrophil axis. These findings highlighted CTSB as a crucial drug target in AD and present IsoL as a promising novel candidate for AD treatment.

overall_design: The submission includes ear tissue samples from mice assigned to different experimental groups.Experimental conditions include blank, MC903-induced atopic dermatitis, and Isoliensinine treatment.Biological replicates are included for all groups.

first: Yuxuan

last: Huang


title: Metabolic adaptation of stromal cells to fatty acid drives metastasis of oral squamous cell carcinoma [RNA-Seq]

city: Wuhan

first: Hui

last: Zhao

address: Luoyu Road

institute: Wuhan university

summary: Metabolic adaptation enables cancer cell survival under nutrient stress, but how stromal cells in tumor microenvironment (TME) withstand similar metabolic change remains elusive. Here, we report that fatty acids (FAs), a nutrient with dual roles in energy provision and lipotoxicity, orchestrate a pro-metastatic adaptation program in cancer-associated fibroblasts (CAFs). In patients with oral squamous cell carcinoma (OSCC), the FA transporter CD36 was upregulated not only in cancer cells but also in myofibroblastic CAFs (myoCAFs), where it correlated with more advanced metastasis stage. Among 5 kinds of FAs enriched in OSCC tissues, palmitic acid (PA) potently activated myoCAFs phenotypes across 2D, 3D, and organoid co-culture models. In vivo, PA promoted lymph node metastasis in orthotopic tumors comprising OSCC cells and CAFs, an effect abolished by CD36 knockdown in CAFs. Mechanistically, PA engaged chromatin occupancy of H3K27ac at multiple genes including IRE1 and TMBIM6, two stress-adaptive regulators. Transcription of IRE1 and TMBIM6 in CAFs was regulated by CCAAT/enhancer-binding protein γ (CEBPG) through an enhancer-dependent manner. Disruption of the CEBPG–IRE1/TMBIM6 axis attenuated myoCAFs properties and abrogated PA-driven metastasis. Our results unveil a stromal metabolic checkpoint and establish CEBPG-enhanced stress resilience as a therapeutic target to curtail metastasis.

overall_design: To investigate how PA influences CAF phenotype, we performed RNA sequencing on two CD36-high CAF lines treated with or without PA.

first: Yiling

last: Duan

first: Yitong

last: Li

first: Yufei

last: Wu

first: Rui

first: Xiao

last: Yang

first: Zhengjun

last: Shang


title: Transcriptomic profiling of lung tissues from a rat model of acute respiratory distress syndrome and vagus nerve stimulation

city: Dalian, Liaoning

first: Ye

last: Gao

address: No.467, Zhong Shan Street

institute: Second Affiliated Hospital of Dalian Medical University

summary: This dataset contains bulk RNA-sequencing profiles generated from lung tissues of Sprague–Dawley rats subjected to cecal ligation and puncture (CLP)-induced acute respiratory distress syndrome (ARDS), with or without right cervical vagus nerve stimulation (VNS).

overall_design:
Four experimental groups were included (n=5 per group):
(1) Sham control, receiving midline laparotomy with gentle cecum manipulation but no ligation or puncture;
(2) ARDS, induced by CLP;
(3) Sham + VNS, sham-operated rats receiving right cervical VNS;
(4) ARDS + VNS, CLP-induced ARDS rats receiving right cervical VNS.


title: Discovery of myrsinane diterpenoids from Euphorbia prolifera as a new type of anti-liver fibrosis agents that inhibit PI3K-AKT signaling pathway

city: Guangzhou

first: 雷名

last: 吴

address: sun-yat san university

institute: 中山大学药学院

summary: Liver fibrosis represents an unmet clinical need. Building on the high screening hit rate of Euphorbiaceae diterpenoids in our previous anti-fibrotic campaigns, we constructed a library of 29 myrsinane diterpenoids from the roots of Euphorbia prolifera in the current study. This collection features three skeletal subtypes and includes 13 new compounds, euphpronoids A-M (1-13), whose structures were elucidated by comprehensive spectroscopic analyses, ECD calculations, chemical correlation, and single-crystal X-ray diffraction. Anti-liver fibrosis screening of this library in TGF-β1-stimulated LX-2 cells revealed ten compounds that significantly suppressed fibronectin (FN) expression. The most active hit, compound 11, dose-dependently reduced the protein levels of FN, α-smooth muscle actin, and collagen I. Mechanistic studies indicated that 11 exerts its anti-fibrotic effect by inhibiting the PI3K-AKT signaling pathway. These findings underscore the potential of the myrsinane scaffold as a promising structural motif for anti-liver fibrosis drug development.

overall_design: LX-2 cells mRNA profiles of treatment with TGF-β1+ DMSO or TGF-β1 + 10 μM 11 for 48 h.

first: Sheng

last: Yin

first: Dong

first: Lu

last: Gan

first: Wei

last: Liu

first: Shuqi


title: Translated retained intron 11 sequence confers pathological properties to Tau in Alzheimer’s disease

city: Singapore

first: Yow-Yong

last: Tan

address: 1 Research Link

institute: Temasek Life Sciences Laboratory

summary: The pathological aggregation of Tau protein into oligomers and fibrils plays a central role in Alzheimer's disease (AD). Here, we explore the biochemical and cellular properties conferred by a unique 19-amino acid intronic peptide found exclusively in the Tau11i isoform. We demonstrate that this intronic peptide mediates robust formation of high molecular weight (HMW) oligomers that resist denaturing and reducing conditions, distinguishing Tau11i from other Tau isoforms lacking this sequence. Tau11i also uniquely forms stable heterodimers with Tau441, suggesting a role in the propagation of Tau pathology. Additionally, the intronic peptide enhances Tau11i’s liquid-liquid phase separation (LLPS), a critical early event associated with pathological aggregation. In vitro assays showed that Tau11i aggregates into β-sheet-rich fibrils more efficiently than other Tau isoforms, significantly facilitating fibril formation and cellular seeding in Tau biosensor cells. Transcriptomic profiling indicated substantial dysregulation in neuronal pathways involving immune response, synaptic function, and metabolism, with Tau11i-expressing neurons closely mirroring the gene expression patterns of AD neurons, particularly the AT8-negative subtype. Furthermore, Tau11i specifically interacts with stress granule-associated RNA-binding proteins, notably PABPC1, implicating it in stress granule dynamics and RNA homeostasis. Collectively, these findings identify the intronic peptide as a critical factor driving Tau11i-specific oligomerization and early-stage molecular alterations associated with Alzheimer's disease, highlighting its potential as a novel therapeutic target distinct from classic Tau pathology.

overall_design: RNA-seq profilling of isogenic control neuron and Tau expressing neurons (Tau441 and Tau11i) at day 55 of differentiation from human NSC

first: Zhen-Kai

last: Ngian

first: Jiazi

first: Chin-Tong

last: Ong


title: Genome-wide maps of chromatin state changes upon Ano1 deficiency in mouse aortic smooth muscle cells

first: Sijia

last: Liang

address: 74 Zhongshan 2 Rd

department: Pharmacology

institute: Sun Yat-Sen University

summary: To explore the role of smooth muscle cell (SMC) Ano1 in atherosclerosis, Ano1 SMC-sepcific knockout mice (Ano1<SMCKO>) and the control mice (WT<SMC>) were injected with AAV-PCSK9DY followed by feeding a high-fat diet for 12 weeks. Subsequently, mouse aortic SMCs (MASMCs) were isolated and subjected to Chip sequencing (ChIP-seq) analysis.

overall_design: ChIP-seq was performed to analysis the chromatin state changes and transcriptional factor MAFK enrichment in MASMCs from HFD-fed Ano1<SMCKO> and WT<SMC> mice.

first: Si-Jia


title: Ketogenic diet dampens excitatory neurotransmission by shrinking synaptic vesicle pools

city: Saint Louis

first: Marion

middle: Isabelle

last: Stunault

state: MISSOURI

address: 660 S Euclid Ave

institute: Washington University School of Medicine

summary: The ketogenic diet (KD) is a common dietary intervention for treating seizures in intractable childhood epilepsies and has been proposed to improve disease outcome in neurodegenerative disorders. Despite its clinical applications, we know little about how this diet impacts brain circuitry and neuronal function to elicit its protective effects. Here, we examined the impact of the KD on hippocampal function through integrative analysis of gene expression, epigenetics and neurotransmission.  We found that KD induces profound transcriptional reprogramming of the hippocampus, including altered expression of numerous synaptic genes. Proteomic analysis of histone variants and post-translational modifications also revealed significant changes in activating and repressive epigenetic marks in the hippocampus of KD mice. To determine how transcriptional and epigenetic rewiring of the hippocampus under KD impacts neurotransmission, we performed electrophysiological recordings to examine synaptic dynamics and synaptic summation at CA3-CA1 synapses. We found that KD diminishes synaptic gain and dampens short-term plasticity at excitatory synapses, resulting in reduced summation of synaptic inputs at the circuit level. We determined that the dampening of synaptic gain was due to a reduction in size of the readily releasable as well as the total of synaptic vesicles in excitatory but not inhibitory synapses. Our findings show that the ketogenic diet triggers synaptic remodeling in the hippocampus, driven by broad transcriptional and epigenetic changes that reduce synaptic vesicle pools and short-term plasticity at excitatory synapses ultimately dampening excitatory synaptic gain and integration at the circuit level. These synaptic adaptations may represent a major mechanism underlying the anti-epileptic effects of this diet.

overall_design: RNAsequencing analysis of the hippocampus of young and Adult mice fed either a chow or ketogenic diet.

first: Pan-Yue

last: Deng

first: Anjali

last: Yadav

first: Erica

last: Periandri

first: Francisca

last: de Luna Vitorino

first: Michael

last: Thomsen

first: Jasmin

last: Sponagel

first: Amelia

last: Barfield

first: Renzelle

last: Ponce

first: Layla

last: Foroughi

first: Benjamin

last: Garcia

first: Gabor

last: Egervari

first: Vitaly

last: Klyachko

first: Ghazaleh

last: Ashrafi


title: cMaf supports Zeb2 expression for primitive hematopoiesis (FL mono RNA-seq)

first: Jing

last: Chen

address: 600 S Euclid Ave

institute: Washington University in St. Louis

summary: Tissue-resident macrophages (TRMs) are essential for tissue homeostasis and play a key role in disease and pathology. They originate from distinct waves of hematopoietic progenitors, including primitive, transient-definitive, and definitive hematopoiesis. We found that loss of the Zeb2 ‒165kb enhancer impairs monocyte development and alters TRM transcriptional landscapes, with only HSC-derived monocytes requiring Zeb2 for their development. In Zeb2∆‒165kb mice, primitive TRMs persist in tissues due to the lack of replacement by later hematopoietic waves, and Maf is required for maintaining Zeb2 expression in primitive macrophages.

overall_design: TRMs were isolated from the lung, liver, brain and spleen of wildtype and Z165KO mice and performed bulk RNA-seq.

first: Theresa

middle: L

last: Murphy

first: Kenneth


title: Inflammation in a severe model of dystrophic cardiomyopathy contains a high proportion of T-cells that contribute to onset of pathology

city: Columbus

first: Jill

last: Rafael-Fortney

state: OH

address: 460 W. 12th Ave

department: Physiology & Cell Biology

institute: The Ohio State University

summary: Duchenne muscular dystrophy (DMD) is a severe neuromuscular disorder characterized by progressive muscle degeneration and cardiomyopathy leading to heart failure. While the inflammatory environment in dystrophic skeletal muscle has been well-studied, little is known about inflammation in the progression of DMD cardiomyopathy due to the lack of adequate animal models. To address this, we developed the Fiona/dko mouse model, which exhibits severe, isolated dystrophic cardiomyopathy. In this study, we used Fiona/dko mice to characterize the immune cell composition in dystrophic heart and investigated the contribution of T-cells to the onset and progression of cardiac pathology. Flow cytometry analysis revealed that T-cells constitute a significant proportion of the immune cell population in Fiona/dko hearts, in contrast to the predominantly myeloid signature observed in dystrophic skeletal muscle. Furthermore, we demonstrated that T-cell infiltration precedes the development of cardiac fibrosis and dysfunction in Fiona/dko mice and that depletion of circulating CD3+ T-cells ameliorates early pathology, suggesting a role for T-cells in the initiation and persistence of dystrophic cardiomyopathy. These findings highlight the distinct inflammatory environment in the dystrophic heart and provide new insights into the pathogenesis of DMD cardiomyopathy, paving the way for the development of targeted anti-inflammatory therapies.

overall_design: To investigate gene expression differences between more severe cardiomyopathy in Fiona/dko mice compared to less severe Het/Fiona mice, 9-month-old mice of each genotype, including males and females for each, were dissected and RNA was extracted from heart ventricles to send for bulk RNA sequencing.

first: Arden

middle: B

last: Piepho

first: Swathy

last: Krishna


title: Dissecting the intra- and intertumoral heterogeneity of adrenocortical carcinoma by single-cell multi-omics analyses

city: Chengdu, Cihna

first: Xaingyu

last: Pan

state: Sichuan

address: No.17 Renming road section3

department: State Key Laboratory of Biotherapy, West China Hospital, Sihcuan University.

institute: Sichuan University

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

overall_design: Refer to individual Series


title: IL-9 in psoriasis: human endothelial cells and murine T cells

city: Pittsburgh

first: Daniella

last: Schwartz

state: PA

address: 200 Lothrop St

institute: University of Pittsburgh

summary: Atherosclerotic cardiovascular disease (ASCVD) is a leading cause of death in patients wiht systemic autoimmune and inflammatory diseases. The inflammatory cytokine interleukin 9 (IL-9) has been linked to ASCVD atherogenesis, raising fundamental questions about the populations in which and the mechanisms by which IL-9 drives ASCVD, leading us to investigate IL-9 in psoriasis. This incuded mRNA sequencing of IL-9+ and IL-9- circulating CD4+ T cells from INFER (IL-9 reporter) mice treated with imiquimod to induce psoriatic inflammation, as well as vehicle vs. IL-9-treated primary human aortic endothelial cells

overall_design:
Experiment 1: mRNA sequencing of IL-9+ and IL-9- circulating CD4+ T cells from INFER (IL-9 reporter) mice treated with imiquimod for 6 weeks to induce psoriatic inflammation
Experiment 2: mRNA sequencing of primary human aortic endothelial cells (HAoEC) exposed to IL-9 vs. vehicle for 16 hours


title: The Piezo1-ATF3-PPP1r15a axis transduces mechanical stress into apoptosis in glioma under low-intensity focused ultrasound

status: Public on Dec 25 2025

city: Harbin

first: mingming

last: li

address: No. 2075, Qunli Seventh Street

department: Department of Qunli Ultrasound

institute: The First Affiliated Hospital of Harbin Medical University

summary: This study aims to evaluate the therapeutic effects of LIFU on GBM and investigate its mechanisms of action.

overall_design: U251 cells were exposed to LIFU (1 W/cm2) for 40 s, followed by three bioduplications, and RNA was extracted using Trizol. Nuohe Zhiyuan (Tianjin, China) performed RNA sequencing and analysis. Then, it was subjected to Illumina sequencing.

first: Mingming

last: Li

first: Weidong

last: Wang

first: Jian

last: Jiang

first: Yingxuan

last: Mao

first: Mingwei

last: Zhu

first: Pengfei

last: Liu

first: Xiuhua

last: Yang


title: DNA methylation of K562 and KU812 cells sensitive and resistant to imatinib.

city: Kharghar

first: Rukmini

last: Govekar

state: Maharashtra

address: Sector 22, Utsav Chowk-CISF Rd, Owe camp

department: Cancer Research Institute

country: India

institute: Advanced centre for Treatment, Research and Education in Cancer

type: Methylation profiling by genome tiling array

summary: CML-CP Patients showing resistance to Imatinib, due to Bcr-Abl mechanisms of resistance  are treated with 2nd and 3rd generation TKIs but some non-responders shown Bcr-Abl independant mechanism of resistance. We hypothesize that this could be due to activation of novel pathway, or activation of downstream molecules of Bcr-Abl pathway. In this study we have performed Transcriptomics and epigenomics analysis of K562 and KU812 CML-BC cell sensitive and resistant to imatinib, ITGB3  showed high transcript levels, and was also  hypomethylated in K562/R cells as compared to sensitive counterparts and showed higher protein levels  in both K562 and KU812 resistant cell lines. Previous studies in the lab also showed  ITGB1 as a differentiator in proteomic analysis and further on-going studies indicate its role in resistance. ITGB1 was however not modulated at transcriptional level.  The protein levels of ITGB3 were significantly increased in resistant cells (K562; KU812: while those of ITGB1 were significantly decreased in resistant cells (K562; KU812. With the known switching of integrins, whether higher expression of ITGB3 had a role in modulating the levels of transcriptionally non-regulated ITGB1 was investigated in K562/S cells with ITGB1 knocked down (KD)  protein levels of ITGB3 were upregulated as compared to VC. Similarly,  knock down of ITGB3 in K562/R resulted in increased level of  ITGB1 protein. These striking results confirmed switching of integrins and explained reduced levels of ITGB1 despite no alteration at genomic or transcriptomic level in resistant cells.

overall_design: The Infinium HumanMethylation850 (EPIC array)  was performed for detection of differential methylation btetween 2 comparisons in 4 samples of K562 and KU812 cells sensitive and resistant to imatinib.

first: Shashi

last: Kumari

first: Rahul

last: Mojidra

first: Mythreyi

last: Narasimhan


title: DNA methylation of PLAG1 KD and VC cells resistant to imatinib.


title: cMaf supports Zeb2 expression for primitive hematopoiesis (CUT&RUN)

first: Jing

last: Chen

summary: Microglia arise exclusively from yolk sac (YS) progenitors during primitive hematopoiesis, while other tissue resident macrophages (TRMs)originate during transient-definitive and definitive hematopoiesis. Macrophages require the transcriptional repressor Zeb2 for development, and macrophages developing during definitive hematopoiesis require the ‒165 kb Zeb2 enhancer. However, microglia develop normally in Zeb2 ‒165kb mice lacking this enhancer, indicating that a distinct genetic program supports macrophage development in primitive hematopoiesis. Here, we identify the molecular basis that distinguishes macrophage development in primitive vs. definitive hematopoiesis. We show that all tissue resident macrophages (TRMs) that develop in Zeb2 ‒165kb mice arise exclusively during primitive hematopoiesis, showing that even erythro-myeloid progenitors (EMPs) from the transient-definitive stage rely on the ‒165 Zeb2 enhancer. Next, we identified the transcription factors Maf and Jun as being expressed by yolk sac (YS) progenitors during primitive hematopoiesis, but not by progenitors during definitive hematopoiesis. Further, we find that Maf and Jun together induce Zeb2 expression independently of the ‒165 kb Zeb2 enhancer and restore macrophage development from adult bone marrow progenitors in Zeb2 ‒165kb mice.  Finally, Maf-deficient embryos show severe ablation of microglia development, confirming the in vivo requirement for Maf in supporting Zeb2 during primitive hematopoiesis. These results illustrate distinct transcriptional pathways controlling macrophage development during primitive and subsequent waves of hematopoiesis.

overall_design: Lin- bone marrow cells were isolated from Zeb2 ‒165kb mice and overexpressed with Maf-hCD4 and Jun-Thy1.1 or empty vector controls (hCD4 and Thy1.1). 250k single and double infected cells were sorted and cut&run was performed with antibody against Maf or Jun.

first: Chen

last: Jing

first: Murphy

last: Theresa

last: Kenneth


title: Synergistic Protective Effects of Ginsenoside Rb1 and Berberine Against Type 2 Diabetes Mellitus via the GDF15/HAMP Signaling Pathway Throughout the Liver Lobules: Insights from Spatial Transcriptomics Analysis

city: Hangzhou

first: Rongfang

last: Guo

address: 866 Yuhangtang Road, Xihu District

institute: Zhejiang university

summary: Type 2 diabetes mellitus (T2DM) is a significant public health issue with high mortality and morbidity. Ginsenoside Rb1 and berberine, the main bioactive compounds of Panax ginseng and Coptis chinensis, respectively, are known for their hypoglycemic effects. Nevertheless, the synergistic effects and underlying mechanism of ginsenoside Rb1 and berberine on T2DM remain unclear. In this study, we utilized a leptin receptor- deficient (db/db) mouse model to investigate the protective effects of their combination treatment. Our findings demonstrated that the combined use of ginsenoside Rb1 and berberine at a 1:4 ratio had more pronounced effects than the first-line anti-diabetic drug metformin on reducing the weight ratio of white adipose tissue, ameliorating insulin resistance, and improving glucose and lipid metabolism. Using spatial transcriptomics, we revealed that metformin treatment improved gluconeogenesis and lipogenesis only in the periportal zone, while the combination treatment induced improvements throughout the liver lobule, with distinct key targets across different zones, thus underscoring a more comprehensive and nuanced modulation of hepatic metabolism. This may be the key reason why this combination therapy demonstrated superior protective effects against T2DM. Additionally, the reversed expression of the key callback gene Hamp and its regulator Gdf15 following the combination therapy across all zones, along with validation experiments, further suggested that the GDF15/HAMP signaling pathway might be a key mechanism underlying the beneficial effects of ginsenoside Rb1 and berberine against T2DM. This study also indicates a path toward innovative drug cocktails for treating T2DM, offering a holistic approach to regulate the entire liver lobule metabolism.

overall_design: Total 171 areas of interest representing three zones of liver zonation from control group (db/m), model group (db/db),  and drug treatment groups (Rb1, BBR, RB, and Met) were sequenced using Nanostring GeoMX Digital Spatial Profiling (DSP) with (v1.0) Mouse NGS Whole Transcriptome Atlas RNA Probeset.

first: Shuying

last: Zhang

first: Anyao

first: Ping

first: Xin

last: Peng

first: Xiaoyan

last: Lu

first: Xiaohui

last: Fan


title: Reprogramming the Tumor Microenvironment with a Membrane-Proximal AXL Antibody to Overcome Immune Checkpoint Blockade Resistance

city: Beijing

first: Zuming

address: No. 30 Shuangqing Road Haidian District

institute: Tsinghua University

summary: Immune-cold tumors failed to respond to immunotherapy due to insufficient lymphocytes infiltration within tumor tissue. How to increase the objective response rate is an urgent challenge. Here, we report the development of a monoclonal antibody (6C5) that specifically targets the membrane-proximal epitope of receptor tyrosine kinase AXL, which modulates the anti-tumor immunity. Unlike traditional membrane-distal AXL antibodies, 6C5 significantly enhanced innate immune sensing by promoting macrophage-mediated antigen uptake and type I interferon production via the MyD88 pathway. This reshaped the tumor microenvironment , further boosting CD8+ T cell infiltration and effector function. However, AXL antibody treatment concurrently induced a suppressive subset of PD-1hiFoxp3-CD4+ T cell, attenuating antitumor responses. The combination of AXL Ab with dual immune checkpoint blockade (anti-PD-1 plus anti-CTLA-4) or PD-1-targeted IL-2 fusion protein therapy mitigated this immunosuppression, achieving potent tumor regression and durable immune memory. Our findings demonstrate that membrane-proximal AXL targeting antibody effectively converts immune-cold tumor microenvironment, overcoming resistance to both conventional and next-generation immune checkpoint inhibitors.

overall_design: Tumor-bearing mice treated with an anti-AXL antibody. After treatment, tumors were collected and enzymatically dissociated into single-cell suspensions. CD4+T subsets were subsequently isolated by fluorescence-activated cell sorting (FACS) and subjected to RNA sequencing.

first: Shuai

last: Cao


title: A high-quality chromosomal-level reference genome of Dendrobium nobile L. provides new insights into the biosynthesis and accumulation of picrotoxane-type sesquiterpenoid alkaloids

city: Guiyang

first: Songtao

last: He

state: Guizhou

address: Bachelor's Road, Sunshine Community Service Center, Huaxi District

institute: Guizhou university

summary: Transcriptome data of sequencing at both ends of different tissues in Dendrobium officinale

overall_design: Six tissues of Dendrobium officinale,two duplications, sequenced at both ends

first: Dandan

last: Li

first: Qiuyue

first: Qunwei

last: Han

first: Kaijie

first: Ronghui

last: Gu

first: Guangchong

last: Zhou

first: Houlin

last: Yu

first: Yiyong

last: Zhao

first: Mingjin

last: Huang