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

city: Stony Brook

first: Harold

last: Bien

state: NY

address: 100 Nicolls Road

institute: Stony Brook University

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

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

first: Abigail

last: Booth

first: Giuseppe

last: Caso

first: Barbara

last: Rosati

first: Richard

middle: Z

last: Lin


title: The CXCL10/CXCR3 axis is essential for sustaining immunological dormancy in triple-negative breast cancer

status: Public on Feb 02 2026

city: Bristol

first: Qiang

last: Lan

address: Biomedical Sciences Building, University Walk

department: School of Cellular and Molecular Medicine

country: United Kingdom

institute: University of Bristol

type: Expression profiling by high throughput sequencing

summary: Immune surveillance plays a pivotal role in controlling tumor emergence, dormancy and progression, including in breast cancer. Despite its potential clinical relevance, the mechanisms governing dormancy initiation, maintenance and escape, as well as the molecular mediators involved, remain poorly understood. Here, we identify the interferon-inducible chemokine CXCL10 and its receptor CXCR3 as key regulators of immunological dormancy in triple-negative breast cancer (TNBC). By transcriptomic profiling, we observed high expression of Cxcl10 in dormant cells in two different orthotopic, syngeneic models of breast cancer dormancy (D2.0R and 4T1-MR20). Genetic silencing of Cxcl10 in dormant cells or pharmacological blockade of CXCR3 in vivo led to early tumor onset and rapid growth in immunocompetent mice. In contrast, dormant cells effectively formed tumors in immune-deficient mice independently of Cxcl10 status, demonstrating that the CXCL10/CXCR3 axis-mediated dormancy requires a functional immune system. Further analysis confirmed that Cxcl10 silencing altered the local immune microenvironment, reducing CD4+ and CD8+ T cell infiltration while increasing the presence of granulocytic Myeloid Derived Suppressor Cells and Natural Killer cells. Moreover, Cxcl10 silencing significantly increased the burden of tumor cells disseminated to the lung. Leveraging these findings, we identified a CXCL10-mediated dormancy signature that predicts improved overall survival in TNBC patients. Our findings have identified a new mechanism modulating breast cancer dormancy with two important clinical implications: the CXCL10/CXCR3 axis as a potential therapeutic target for improving survival of patients with TNBC, and the CXCL10-dependent dormancy signature as a tool for identifying these patients.

overall_design: RNAseq profiling of in vitro cultured wildtype D2A1 and D2.0R, and knockdown varients of dormant D2.0R (D2.0R-shCTL and D2.0R-shCXCL10) cells.

first: Alev

last: Yilmaz

first: Curzio

last: Rüegg


title: Integration of tumor-specific dendritic cell and antibody therapy within tumor drives innate and adaptive anti-cancer immunity [PanCancer_IO360_NanoString]

city: Tampa

first: jiqiang

last: yao

address: 12902 USF Magnolia Drive

country: USA

institute: moffitt cancer center

summary: Comparison of gene expression profiles of HER2+ murine mammary carcinoma treated with HER2 DC1, anti-Sema4D, and combination of both HER2 DC1 and anti-Sema4D therapy

overall_design: Performed gene expression comparison by analyzing gene expression values using the oncology nanostring panel (GPL32728)

first: Saurabh

last: Garg

first: Brian

last: Czerniecki


title: Hepatic NIK Protects Against Ethanol-Induced Steatosis by Stabilizing INPP5B to Suppress PI3K/AKT/ACLY Lipogenesis

city: Nanjing

first: Wen

last: Zhang

address: No. 101 Longmian Avenue, Jiangning District, Nanjing, China

country: China

institute: Nanjing Medical University

summary: Alcohol-associated liver disease (ALD) imposes a major global health burden, yet lacks FDA-approved targeted therapies. While NF-κB-inducing kinase (NIK) is recognized for its dual roles in hepatic inflammation and lipid metabolism, its specific function in ALD pathogenesis remained incompletely defined. Contrary to its established protective role against high-fat diet-induced steatosis, this study reveals a paradoxical protective function of hepatic NIK in chronic ethanol-induced steatosis. We demonstrate that liver-specific NIK deficiency unexpectedly exacerbates hepatic steatosis in chronic ethanol-fed mice. This aggravation occurs via activation of the PI3K/AKT-ATP Citrate Lyase (ACLY) signaling pathway, promoting lipogenesis. Importantly, NIK overexpression reversed steatosis in deficient mice, independent of the non-canonical NF-κB effector p52. Mechanistically, proteomics and functional studies identified Inositol polyphosphate-5-phosphatase b (INPP5B), a negative PI3K/AKT regulator, as a key downstream target. NIK stabilizes INPP5B by suppressing its ubiquitination and enhancing its interaction with Adaptor protein APPL1, thereby inhibiting PI3K/AKT/ACLY signaling. These findings unveil a novel, kinase/scaffold-dependent role for NIK in mitigating ethanol-induced steatosis through INPP5B stabilization and highlight its context-dependent, double-sided effects in ALD progression, offering new insights for therapeutic strategies.

overall_design: NIKF/F and NIKHKO mice were treated with the Lieber-DeCarli ethanol liquid diet containing 5% ethanol for 4 weeks


title: Integration of tumor-specific dendritic cell and antibody therapy within tumor drives innate and adaptive anti-cancer immunity [Immunology_NanoString]

overall_design: Performed gene expression comparison by analyzing gene expression values using the Immunology nanostring panel (GPL32407)


title: Integration of tumor-specific dendritic cell and antibody therapy within tumor drives innate and adaptive anti-cancer immunity [Myeloid_Innate_Immunity_NanoString]

overall_design: Performed gene expression comparison by analyzing gene expression values using the myeloid nanostring panel (GPL31165)


title: CLK1 Promotes MDSC Trafficking and Reprograms the Tumor Microenvironment by activating Hippo/YAP signaling in Colorectal Cancer

city: Guangzhou

first: Peisi

last: Li

state: China

address: Yuancunerheng Road

institute: Department of Colorectal Surgery, The Sixth Affiliated Hospital of Sun Yat-sen University

summary: Colorectal cancer (CRC) is a highly heterogeneous malignancy, characterized by complex interactions between tumor cells and the immune system. The tumor microenvironment (TME) plays a crucial role in CRC progression and response to therapy. However, its regulatory mechanisms remain poorly understood due to the genetic and phenotypic diversity of tumor cells. In this study, we investigated the tumor-intrinsic factors contributing to TME formation and evaluated genotype-based combination strategies to enhance the efficacy of immunotherapy in CRC. RNA sequencing, single-cell analysis, and immunohistochemistry were conducted to identify pro-oncogenic proteins associated with low immune activation. Functional studies using in vitro co-culture systems, subcutaneous CRC tumor models, flow cytometry, and immunohistochemistry revealed the pivotal role of CLK1 in tumor progression and immunosuppressive TME remodeling. Mechanistically, CLK1 activation led to hyperactivation of the Hippo signaling pathway, promoting nuclear translocation of YAP and subsequent transcriptional upregulation of the chemokine CXCL1. Elevated CLK1 expression correlated with increased infiltration of myeloid-derived suppressor cells (MDSCs) and impaired antitumor immune responses. Knockdown of CLK1 significantly reduced MDSC recruitment and restored CD8+ T cell activity. Moreover, combined CLK1 knockdown and anti-PD1 therapy synergistically enhanced intratumoral CD8⁺ T cell infiltration and elicited robust antitumor responses in murine CRC models. Collectively, our findings identify the CLK1-Hippo/YAP-CXCL1 signaling axis as a key regulator of immune evasion and TME remodeling in CRC, and highlight its potential as a therapeutic target to improve the efficacy of immune checkpoint blockade.

overall_design: RNA-seq file of MC38 cells treated with or without CLK1 inhibitor TG003.


title: Integrated Spatial Transcriptomics and Single-Cell RNA Sequencing Reveal Lars2-Mediated Spatiotemporal Dynamics of Myocardial Remodeling in a Mouse Model of Transverse Aortic Constriction (TAC)

city: Shanghai

first: Hanwen

last: Ni

state: Shanghai

address: 197th, Ruijin 2nd rd.

department: Department of Cardiology

institute: Ruijin Hostpital, School of Medicine, Shanghai Jiao Tong University

summary: Multi-omics approaches have emerged as a cornerstone in medical biology, offering an integrative perspective on tissue and cellular composition, gene expression patterns, functional states, and metabolic dynamics. In this study, we employed multi-omics methodologies, combining spatial transcriptomics (ST) and single-cell RNA sequencing (scRNA-seq), to perform large-scale bioinformatics analysis on heart samples from Transverse Aortic Constriction (TAC) mouse models at various stages of disease progression. The aim was to investigate the spatial and temporal characteristics of cellular distribution, gene composition, and associated functional changes within the myocardium in response to pressure overload. For the first time, the pathophysiology of myocardial hypertrophy in this model is described through the integrated lens of spatial and single-cell transcriptomics. The spatial transcriptomics analysis revealed a uniform cellular distribution across the heart tissue in TAC mice at different disease stages. However, substantial shifts in cellular composition were observed, with the most significant alterations occurring in cluster 1, which primarily involved changes in fibroblasts and macrophages. Single-cell RNA sequencing further demonstrated that the most notable changes in cellular composition occurred at the TAC-4W stage, characterized by a reduction in fibroblast and macrophage populations and an increase in immune cell subsets, such as neutrophils and T cells. By TAC-6W, the cellular composition returned to a state comparable to that observed at TAC-2W. Further analysis integrating both spatial and single-cell transcriptomes highlighted cluster 1 as the site of the most prominent microenvironmental changes, predominantly involving T cells and macrophages. Notably, the genes Lef1, Ccr7, Sell, and Lars2 were identified as significantly differentially expressed in these cells—an observation not previously reported. In particular, the expression of Lars2 exhibited dynamic modulation throughout disease progression. While its expression at TAC-2W did not differ significantly from controls, Lars2 expression peaked at TAC-4W, only to decline at TAC-6W. This study provides a comprehensive characterization of myocardial hypertrophy in the TAC mouse model, leveraging the power of spatial transcriptomics and single-cell RNA sequencing. The findings offer novel insights into the spatial and temporal dynamics of cellular distribution and gene expression, advancing our understanding of the molecular mechanisms underpinning cardiac remodeling in response to pressure overload.

overall_design: Eight-week-old male C57BL/6J mice (25–27 g) were randomly assigned to sham or transverse aortic constriction (TAC) groups. Hearts were harvested at 2, 4, and 6 weeks after surgery. Cardiac tissues were processed for both spatial transcriptomics (10x Genomics Visium) and single-cell RNA sequencing (10x Genomics Chromium 3’ v3.1). Sequencing was performed on the Illumina NovaSeq 6000 platform. This design enabled the integration of temporal, spatial, and single-cell transcriptomic data to characterize myocardial remodeling under pressure overload.

first: Feng

last: Liang

first: Huanhuan

last: Huo

first: Xuechao

last: Feng

first: Ben

last: He


title: esBAF and INO80 fine-tune subcompartments and differentially regulate enhancer-promoter interactions [HiC]

city: Pittsburgh

first: Sarah

middle: J

last: Hainer

state: PA

address: 4249 Fifth Ave

department: Department of Biological Sciecnes

institute: University of Pittsburgh

summary: The genome is compacted in the nucleus through a hierarchical chromatin organization, ranging from chromosome territories to compartments, topologically associating domains (TADs), and individual nucleosomes. Nucleosome remodeling complexes hydrolyze ATP to translocate DNA and therefore mobilize histone proteins. While nucleosome remodeling complexes have been extensively studied for their roles in regulating nucleosome positioning and accessibility, their contributions to higher-order chromatin architecture remain less well understood. Here, we investigate the roles of two key nucleosome remodelers, esBAF and INO80, in shaping 3D genome organization in mouse embryonic stem cells. Using Hi-C, we find that loss of either remodeler has minimal effects on global compartment or TAD structures. In contrast, subcompartment organization is notably altered, suggesting that esBAF and INO80 contribute to finer-scale chromatin topology. To overcome the limited resolution of Hi-C for detecting regulatory loops, we employed promoter capture Micro-C, which revealed that the loss of esBAF or INO80 alters a subset of promoter anchored looping interactions. Although these changes occur at distinct genomic loci for each remodeler, the affected sites are commonly enriched for bivalent chromatin regions bound by OCT4, SOX2, and NANOG, as well as BRG1 and INO80 themselves. Together, our findings reveal that esBAF and INO80 selectively influence subcompartment identity and enhancer–promoter communication at key regulatory loci, highlighting a previously underappreciated role for nucleosome remodelers in higher-order chromatin organization.

overall_design: Hi-C

first: Braulio

last: Bonilla

first: Benjamin

last: Patty

first: Snehal

middle: V

last: Sambare

first: Job

last: Dekker

first: Thomas

middle: G

last: Fazzio


title: Characterization of a Novel Transmembrane Activating STING Agonist using Genetically Humanized Mice

city: Beaverton

first: Victor

middle: Robert

last: DeFilippis

state: Oregon

address: 505 NW 185th Ave.

department: Vaccine and Gene Therapy Institute

institute: Oregon Health and Science University

summary: Transcriptome analysis of bone marrow derived dendtitic cells from C57Bl/6 parental and genetically humanized STING (huSTING) mice treated ex vivo with two STING agonists and LPS

overall_design: We analyzed RNA harvested from BMDC treated for 6 hours in duplicate treatments using the Affymetrix Clariom S platform. Array data was processed by Trancriptome Analysis Console (Affymetrix).

middle: R

first: Nobuyo

last: Mizuno

first: Jinu

last: Abraham

first: Ian

last: Rose

first: Laura

last: Springgay

first: Kevin

last: Jimenez-Perez

first: Omer

last: Rasheed

first: David

last: Burkhart

first: Shannon

last: Miller

first: Dylan

last: Boehm

first: Takeshi

last: Ando

first: Daniel

last: Streblow

first: Janine

last: Ward

first: Elias

last: Haddad

first: Roshell

last: Muir

last: Joyner

first: Uddav

last: Pandey

first: Ahmad

last: Junaid


title: Cytochrome P450 1B1 directs pathogenic-Th17 cell generation and autoimmune disease by maintaining cellular redox homeostasis and mitochondrial function

city: Wuhan

first: yunqing

last: sun

state: 洪山区

address: Luoyu Road 237#

institute: wuhan university

summary: Th17 cells are heterogenous. Pathogenic Th17 cells induced by IL-23, have been well implicated in inflammatory bowel disease (IBD), while the underlying mechanisms remain unclear. Here, we revealed that cytochrome P450 1B1 (CYP1B1) is specifically upregulated in mice and human colitis disease. With CYP1B1 knockout mice, we found that CYP1B1 specifically promoted IL-6+IL-1b+IL-23 induced pathogenic-Th17 cells while has no effect on TGFb1+IL-6-induced homeostatic Th17 cells. CYP1B1 deficiency significantly ameliorated disease severity in both DSS-induced colitis and colitis-associated colorectal cancer (CAC) models, and impaired pTh17 responses in vivo. Additionally, CYP1B1 deficiency in T cells disrupted glutathione/ROS homeostasis, leading mitochondrial dysfunction and apoptosis by pTh17 cells. ROS elimination by NAC or ectopically GSS expression increased mitochondria fitness and promoted pTh17 cell generation. Taking together, our findings uncover a CYP1B1-ROS-mitochonrial axis in driving pTh17 cell generation and proinflammatory function, interfering this hub may be benefit for pTh17 cell-related immunopathology.

overall_design: RNA-seq profiling of wildtype and Cyp1b1-/- mouse CD4 T cells at Day2 pathogenic Th17 differentiation


title: Functional characterization of podocyte-expressed THSD7A in experimental membranous nephropathy

city: Hamburg

first: Ming

last: Huang

address: Martinistrasse 52

department: III. Department of Medicine

country: Germany

institute: University Medical Center Hamburg-Eppendorf

summary: While the pathogenic role of autoantibodies targeting the podocyte protein THSD7A in membranous nephropathy (MN) is well described, the consequences of autoantibody binding for podocyte homeostasis and the function of THSD7A remain unclear. Here, we induced an MN model in control and podocyte-specific Thsd7a knockout (Thsd7a-/-) mice using rabbit anti-THSD7A antibodies, followed by transcriptome and proteome analyses. Anti-THSD7A antibodies in WT mice caused significant loss of key slit diaphragm (SD) proteins such as nephrin and NEPH1, without transcriptional downregulation. Glomeruli showed substantial transcriptomic and proteomic reconfiguration indicative of extensive podocyte injury, including disruptions in podocyte adhesion, cytoskeletal dynamics, and marked upregulation of ubiquitin-proteasome system components, cathepsins and ADAM proteases. Notably, experiments in C3-deficient mice revealed that proteolytic activation and SD protein loss are driven by complement-independent pathways. While Thsd7a-/- mice only displayed a mild phenotype under basal conditions, they were completely protected from MN development upon anti-THSD7A antibody transfer. Finally, interactomic analysis identified a protein complex including THSD7A and integrin α3, linking THSD7A complexes to pathogenic regulation of cytoskeleton, adhesion, and membrane signaling in MN. Thus, anti-THSD7A antibodies induce profound molecular reconfiguration, including dysregulated proteolytic systems via a complement-independent pathway, revealing potential therapeutic targets in MN.

overall_design: Comparative gene expression profiling analysis of bulk RNA-seq data in mouse kidney glomerulus (THSD7A-associated MN vs. control mice).

first: Nicola

middle: M

last: Tomas


title: esBAF and INO80 fine-tune subcompartments and differentially regulate enhancer-promoter interactions [microC]

first: Sarah

last: Hainer

overall_design: micro-C

first: Braulio

last: Bonilla

first: Benjamin

last: Patty

first: Snehal

last: Sambare

first: Job

last: Dekker

first: Thomas

last: Fazzio


title: Characterization and miRNA Profiling of Extracellular Vesicles from Rabbit Oviduct and Uterine Fluids

city: Madrid

first: Lena

last: Arévalo

state: Madrid

address: Avda. Puerta de Hierro, 18

department: Animal Reproduction

country: Spain

institute: INIA-CSIC

type: Non-coding RNA profiling by high throughput sequencing

summary: This study aims to uncover how extracellular vesicles (EVs) influence key reproductive processes by isolating, characterizing, and analyzing the miRNA cargo of these oviductal and uterine fluid-EVs. Small RNA sequencing identified 388 miRNAs in OF-EVs and UF-EVs. However, 4 miRNAs significantly more abundant in OF-EVs, while 17 were significantly more abundant in UF-EVs, indicating potential differences in their roles in embryo-maternal communication. The most abundant miRNAs in both fluids included ocu-miR-148a-3p, ocu-let-7i-5p, and ocu-miR-10b-5p, which are associated with embryo development and implantation. Gene target prediction analysis of the top abundant revealed that miRNAs in OF-EVs regulate key signaling pathways such as MAPK, Hippo, TGF-β, Ras, PI3K-Akt, and mTOR, while UF-EVs are associated with Hippo, PI3K-Akt, FoxO, endocytosis, and mTOR signaling. These pathways are essential for cell proliferation, differentiation, and immune regulation, crucial for embryo-maternal interactions. Our findings suggest that EVs in rabbit reproductive fluids play a fundamental role in early embryonic development and successful pregnancy. These results provide new insights into reproductive biotechnology and veterinary medicine, with potential applications in improving fertility and embryo viability.

overall_design: Characterization, comparison and analysis of the rabbit miRNA cargo of oviductal and uterine fluid extracellular vesicles

first: Yulia

middle: N

last: Cajas

first: Kevin

last: Burbano

first: Carolina

last: Nuñéz-Puente

first: María

last: Millán de la Blanca

first: Maria

last: Iniesta-Cuerda

first: Ana Josefa

last: Soler-Valls

first: Dimitrios

last: Rizos

first: Pilar

last: Rebollar

first: Karina

last: Cañón-Beltrán


title: Endothelial cell-conditioned medium enhanced astrocyte differentiation in cerebral organoids

city: Vestec

first: Zuzana

last: Matusova

address: Prumyslova 595

department: Laboratory of Glial Biology and Omics Technologies

country: Czech Republic

institute: Institute of Biotechnology of the Czech Academy of Sciences

summary: Human brain organoids (hBOs) are self-organizing, three-dimensional structures that recapitulate aspects of early brain development, including astrogliogenesis. However, astrocyte differentiation does not occur until months into the differentiation process, and astrocytes continue to mature for years after that. Astrogliogenesis and astrocyte maturation could be further delayed by innate shortcomings of the model such as a lack of endothelial cells (ECs). Indeed, studies suggest that ECs or EC-derived factors promote astrogliogenesis and astrocyte maturation in vitro. Here, we exposed unguided hBOs to conditioned medium of immortalized human cerebral microvascular ECs (hCMEC/D3 cells) and determined their expression profile on the single-cell level at two time points. We found that EC-secreted proteins do not induce premature astrogliogenesis in hBOs but do affect hBO cellular composition and the maturation of radial glia, which are the precursors to astrocytes. These findings indicate the potential of EC-secreted factors to enhance astrocyte (precursor) maturation in hBOs and emphasize the importance of considering EC effects when aiming to accurately study developing astrocytes using hBOs.

overall_design: Cerebral organoids were cultivated in a medium conditioned by endothelial cells. For scRNA-seq, they were harvested at 64 and 118 days in culture, along with their control counterparts cultivated in normal medium.

first: Lois

last: Kistemaker

first: Lukas

last: Valihrach

first: Elly

last: Hol


title: Patient iPSC-derived brain organoids of neuronopathic Gaucher disease identify imbalances in neural lineages and deficits in interneuron function

summary: Gaucher disease is a rare lysosomal storage disorder caused by autosomal recessive mutations in the GBA1 gene, encoding the lysosomal enzyme glucocerebrosidase. Gaucher disease is classified in 3 different subtypes depending on the presence and severity of neurological affectation, with type 2 resulting in fatal early-onset neuropathology and patients exhibiting developmental delays, seizures and early death. Studies investigating disease mechanisms of neuronopathic Gaucher disease are mainly based on animal models and focus predominantly on late neuronal progression phenotypes. Here, we established a healthy control and Gaucher disease patient iPSC lines and engineered them to obtain isogenic control and disease lines. Using these lines, we generated cortical and subpallial brain organoids in which we identified early-onset lipid dysregulation in form of highly elevated glucosylsphingosine and a posterior increase in gangliosides. Moreover, we uncovered a new phenotype consisting of an increase in more mature inhibitory and excitatory populations at the expnse of a deficit in proliferating and migratory, suggesting a higher susceptibility of specific cell types to Gaucher disease. Interestingly, at the functional level we observed deficits in interneuron function, a clinically significant phenotype as many patients exhibit an excitation/inhibition imbalance leading to treatment-resistant seizures, hastening their decline. In conclusion, our defined human model of Gaucher disease identifies novel and clear phenotypes that can be used for drug screening or aide in development of new therapeutic strategies to ameliorate Gaucher disease.

overall_design: Two cell lines - patient-derived cell line carrying a GBA1 mutation (GD) and GBA1 knock-out (HC-KO) - and their isogenic controls (GD-iso and HC) were used for cultivation of cortical (hCOs) and subpallial organoids (hSOs). These were harvested at day 75 and 150 in culture, several organoids were pooled, and used for the scRNA-seq experiment (16 samples).

first: James

last: Crowe

first: Oskar

last: Zetterdahl

first: Aline

last: Girard

first: Joachim

last: Björklund

first: Madalina

last: Sacultanu

first: Leal

last: Oburoglu

first: Ulf

last: Ellervik

first: Henrik

last: Ahlenius

first: Isaac

last: Canals


title: Distinct tumor immune microenvironmental (TIME) landscapes drive divergent immunotherapy responses in glioblastoma

city: Leuven

first: Gabriele

last: Bergers

address: Herestraat 49

country: Belgium

institute: KU Leuven

summary: Glioblastoma (GBM) exhibits significant molecular heterogeneity leading to variable treatment responses. Despite multimodal therapies, prognosis remains poor, highlighting the need for personalized approaches targeting the tumor immune microenvironment (TIME). Using single-cell RNA sequencing, multiplex immunohistochemistry, and orthotopic mouse models, we characterized distinct TIME subtypes and evaluated responses to anti-angiogenic immunotherapy and myeloid-targeting approaches. We identified three TIME subtypes: TIME-low (immune-excluded with abnormal vasculature), TIME-med (immune-infiltrated with functional T cells), and TIME-high (heavily infiltrated with immunosuppressive myeloid cells and anergic T cells). TIME-low GBMs responded transiently to anti-angiogenic immunotherapy with immunostimulatory T cell shifts, while anti-angiogenic therapy was ineffective in TIME-high GBMs due to immunosuppressive myeloid cells. CD40 agonist treatment worsened outcomes in TIME-high GBMs by increasing immunosuppressive cells and reducing NK recruitment. Conversely, PI3Kγ/δ inhibition combined with anti-angiogenic immunotherapy modestly extended survival in TIME-high tumors. Our study reveals that GBM subtypes require tailored therapeutic strategies, with TIME classification potentially predicting treatment responses and TIME-high tumors requiring myeloid reprogramming to overcome immunosuppression.

overall_design: We performed single-cell RNA sequencing to investigate how different murine GBM models can recapitulate distinct human GBM subtypes, and how tumor cells and the tumor immune microenvironment adapt to different immunotherapies. The study included NSCG (TIME-low) and NFpp10 (TIME-high) murine GBM tumor models under different treatment conditions: untreated (UT) or vehicle control (IgG), BP (B20 + PD-L1), CD40 agonist, and BPI (BP + IPI-145). Tissues were collected at approximately day 14 (after 3 rounds of treatment). Single-cell suspensions were prepared from fresh whole tumor tissues from at least two mice pooled within each treatment group using enzymatic digestion before 10X Genomics single-cell RNA sequencing.

first: Linqian

last: Weng

first: Krish Skandha

last: Gopalan


title: Uncovering the Acetylation Sites of Dnmt3L to Regulate Protein Stability and Potency of Differentiation in Embryonic Stem Cells

city: Seoul

first: DONG-MYUNG

last: SHIN

address: Pungnap-2 dong, Songpa-gu

department: Department of Biomedical Sciences

country: South Korea

institute: University of Ulsan College of Medicine

summary: The epigenetic status, a key mechanism regulating the cellular identity and differentiation potential of pluripotent stem cells (PSCs), dynamically responds to the culture environment, affecting the safe and effective use of PSCs for basic research and therapeutic applications. However, it remains unclear about key mediator(s) for representing the epigenetic signatures of PSCs under distinct culture conditions. Here, we investigated the role of DNA methyltransferase 3-Like (Dnmt3L) in modulating the DNA methylation and differentiation potential of mouse embryonic stem cells (mESCs). Unlike other de novo DNA methyltransferases, Dnmt3L exhibited a uniquely dynamic expression pattern during prolonged 2i-LIF cultures, marked by a rapid post-transcriptional upregulation that sensitively reflected changes in the extracellular environment. Through mass spectrometry, we identified acetylation at lysine-residues K238 and K412 as key factors controlling Dnmt3L protein stability. These modifications critically affected the expression of genes associated with naïve pluripotency and differentiation, especially within germline, neural, and cardiac lineages through locus-specific DNA methylation. Our findings highlight Dnmt3L as a key regulator of epigenetic stability at developmentally critical loci in mESCs, acting as a dynamic responder to changes in the extracellular culture environment. Thus, understanding the regulation mechanism of Dnmt3L could provide insight into the onset of epigenetic aberrations and suggest the optimal culture conditions to preserve epigenetic integrity of ESCs, which have significant implications for regenerative medicine.

overall_design: All animal experiments were approved and performed in accordance with the guidelines and regulations of the Institutional Animal Care and Use Committee of the University of Ulsan College of Medicine (IACUC 2021-12-271). We subcutaneously injected eight-week-old male NOD-PrkdcEM1 mice (JA BIO, Suwon-si,Gyeonggi-do, Korea) with 5x106 cells of each ESC cultured with FBS-LIF medium. The mice and site of injection were monitored for 46 days. Teratomas were recovered by dissection to measure tumor size and for histological examination or for transcriptome analysis at day 21 post-injection. Histological analyses and immunostaining were performed as previously described 5. Mice were randomly allocated to treatment groups (n = 7/group), and the order of cell transplantation, treatment, and evaluation, as well as daily examinations, was randomized. Investigators involved in teratoma size measurements and histological assessments were blinded to the treatment groups.

first: Yun Ji

last: Nam

first: Hyungu

last: Kwon

first: Seungun

last: Lee

first: Dong-Myung

last: Shin

first: Kyunggon

last: Kim


title: L1CAM promotes human endometrial cancer via NF-κB activation

city: Sapporo

first: Hiroyuki

last: Kurosu

state: Hokkaido

address: Kita 15, Nishi 7, Kita-ku

department: Faculty of Medicine and Graduate School of Medicine

country: Japan

institute: Hokkaido University

summary: RNA-seq analysis of human endometrial carcinoma HHUA cells was performed to determine the impact of L1CAM knockdown. Cells were transduced with shRNA targeting L1CAM or shscramble and harvested 48 hours later for total RNA extraction. This dataset provides insight into gene expression changes associated with L1CAM suppression in uterine cancer.

overall_design: L1CAM knockdown using shRNA was performed in a lentiviral system in the HHUA cell line and RNA-seq profiles were obtained.

first: Hiroshi

last: Asano

first: Shugo

last: Tanaka

first: Issei

last: Kawakita

first: Atsushi

last: Niida

first: Hidemichi

last: Watari

first: Koji

last: Taniguchi


title: Antigen-specific immunotherapy with a CD4 hybrid insulin peptide neoepitope arrests CD8 T cell differentiation in islet grafts

city: Aurora

first: James

middle: E

last: DiLisio

state: CO

address: 1775 Aurora Ct

department: Immunology and Microbiology

institute: University of Colorado

summary: Antigen‐specific immunotherapies aim to induce peripheral tolerance in autoreactive T cells without the collateral risks of broad immunosuppression. In type 1 diabetes, certain class II HLA molecules strongly predict disease risk, indicating the centrality of CD4 T cell epitopes in disease. However, CD8 T cells targeting islet-antigens are predominant in human islet infiltrates and critical for disease progression. Understanding how peripheral tolerance induction to CD4 peptide autoantigens can generate the suppression of antigen-specific CD8 T cells is still not entirely understood.  Here, we show that nanoparticles conjugated to a single CD4 T cell epitope, a hybrid insulin peptide, can reshape the fate of antigen‐specific CD8 T cells in islet grafts. Induction of tolerance arrested the functional differentiation of antigen-specific CD8 T cells and restricted their TCR repertoire towards a lower‐avidity public TCR. Antigen-specific CD8 T cells are arrested in part by the expansion of interleukin-10 (IL-10)-producing antigen-specific CD4 regulatory populations that function through indirect suppression of dendritic cell licensing in grafts. Neutralization of IL-10 during hybrid insulin peptide tolerance induction abrogates graft protection, restores CD8 effector differentiation and TCR affinity, and rescues dendritic cell licensing, establishing an IL-10 dependent suppression axis. These findings help explain how antigen‐specific therapy to a single CD4 hybrid insulin peptide epitope can arrest autoreactive CD8 T cell effector fates in transplanted islets, prolonging graft survival.

overall_design: Following syngeneic islet transplant and 2.5HIP-nanoparticle tolerance induction, IGRP-tetramer+ CD8 T cells were sorted by FACS from the graft (8 days post-transplant) from 2.5HIP-nanoparticle treated or control HEL-nanoparticle treated animals and submitted for scRNAseq. CD4 T cells were also sorted in the sequencing event and must be removed by transcript expression of the Cd4 gene to leave the remaining CD8+ IGRP-specific T cells.

first: Kathryn

last: Haskins


title: Integration of tumor-specific dendritic cell and antibody therapy within tumor drives innate and adaptive anti-cancer immunity [Metabolic_Pathways_NanoString]

first: jiqiang

last: yao

overall_design: Performed gene expression comparison by analyzing gene expression values using the Metabolism nanostring panel (GPL30557)

first: Garg

last: Saurabh

first: Czerniecki

last: Brian


title: ZFP148 is a transcriptional regulator of effector CD8+ T cell differentiation [single-cell_multiome]

city: Columbus

first: Tong

last: Xiao

state: OH

address: 2255 Kenny Rd, Room 3130

institute: Pelotonia Institute for Immuno-oncology

type: Genome binding/occupancy profiling by high throughput sequencing

summary: Chronic antigen exposure, as seen in persistent viral infections and cancer, drives CD8⁺ T cells to differentiate into diverse subsets: progenitor/stem-like, effector, and exhausted/dysfunctional cells. While genetic and epigenetic factors influencing these subsets are known, the mechanisms regulating their dynamic balance remain unclear. We identified Zinc-Finger Protein 148 (ZFP148) as a novel transcriptional checkpoint in CD8⁺ T cell effector differentiation. Using a genetic approach that deletes ZFP148 specifically in CD8+ T cells, we performed matched single cell RNA-seq and ATAC-seq on antigen-specific CD8+ T cells.

overall_design: CD44High GP33-41 tetramer+ CD8+ T cells were FACs-sorted from the spleens of control or ZFP148 KO mice 21 days-post lymphocytic choriomeningitis virus (LCMV) Clone 13 (Cl13) infection. After sorting, cells were washed with PBS containing 0.04% BSA, then approximately 10,000 nuclei of either control or ZFP148 KO sample were isolated and processed with the Chromium Single Cell Multiome ATAC + Gene Expression Reagent Kit following manufacture’s manual (10x genomics). Two separate sets of libraries, Gene expression (GEX) and ATAC, were generated from each sample according to manufacturer’s instructions. Pre-sequencing quality control was performed using an Agilent Tapestation. GEX libraries and ATAC libraries were sequenced on an Illumina Novaseq X plus platform by Azenta Life Sciences.

first: Xiao

last: Tong

first: Ma

last: Anjun

first: Li

last: Zihai


title: Single-cell transcriptomic analysis of the normal mouse colon and small intestine

city: Vari

first: Vasiliki

last: Koliaraki

state: Attiki

address: 34 Fleming street

country: Greece

institute: BSRC "Alexander Fleming"

summary: The aim of this study was to characterise the composition, expression profile, and functions of stromal cells, including fibroblasts, endothelial cells, pericytes, and smooth muscle cells, in the healthy mouse colon and small intestine. This data are expected to provide information on stromal cell functions in intestinal homeostasis and can be used as control for different murine intestinal disorders, such as inflammation and cancer.

overall_design: Single-cell RNA sequencing (scRNA-seq) was performed to characterize the transcriptional heterogeneity of normal colon and small intestinal. 10X Chromium Next GEM Single Cell 3' Kit v3.1 sequencing was performed at live stromal cells that were isolated by FACS sorting after the exclusion of epithelial and immune cells.

first: Athanasia

last: Stavropoulou

first: Niki

last: Chalkidi


title: Single-cell transcriptomic analysis of the AOM/DSS-induced tumor stroma

summary: The aim of this study was to characterise the composition, expression profile, and functions of stromal cells, including fibroblasts, endothelial cells, pericytes, and smooth muscle cells, in the microenvironment of AOM/DSS-induced tumors. This data are expected to provide information on stromal cell functions during carcinogenesis and potentially reveal novel targetable mechanisms of stromal activation at the early stages of tumor development.

overall_design: Single-cell RNA sequencing (scRNA-seq) was performed to characterize the transcriptional heterogeneity of the AOM/DSS tumor microenvironment. Tumors were obtained from AOM DSS treated mice. 10X Chromium Next GEM Single Cell 3' Kit v3.1 sequencing was performed at live stromal cells that were isolated by FACS sorting after the exclusion of epithelial and immune cells.


title: ZFP148 is a transcriptional regulator of effector CD8+ T cell differentiation

summary: In the setting of chronic antigen stimulation, such as chronic viral infection and cancer, antigen-specific CD8+ T cells differentiate into a heterogeneous pool of progenitor/stem-like, effector, and exhausted/dysfunctional subsets. Though genetic and epigenetic programs that contribute to the generation of each subset have been reported, how these subsets are dynamically regulated and how their balance can be shifted from exhausted toward cytolytic effector cells remain as outstanding questions. Here, we identified Zinc-Finger Protein 148 (ZFP148) as a novel transcriptional checkpoint for CD8+ T cell effector differentiation. We performed CUT&Tag followed by seuqencing (CUT&Tag-seq) of ZFP148 in activated CD8+ T cells from healthy C57BL/6J mice to identify direct DNA-binding activity of ZFP148.

overall_design: Naïve CD8+ T cells were isolated from the spleens of healthy mice and activated with 5 μg/ml plate-bound anti-CD3 and 2 μg/ml soluble anti-CD28 antibody for 24 hours in 24-well plate. A total of 1 million cells were used for library construction of each target (ZFP148 or IgG control) using the CUT&Tag-seq following the stepwise protocol from Epicypher https://www.epicypher.com/resources/protocols/cutana-cut-and-tag-protocol/. Libraries with equal molar ratio were pooled together. Paired-end sequencing was performed on an Illumina Novaseq X plus platform by Azenta Life Sciences, and 50 million reads were generated for each sample.

first: Zihai

last: Li


title: Induction of anergy in human T lymphocytes by exposure to single amino acid mutated antigens is stochastic

city: Kobe

first: Yoko

last: Nakai-Futatsugi

address: 2-2-3 Minatojima-minamimachi, Chuo-ku

institute: RIKEN

summary: A single RNA sequencing approach using 10x Genomics scRNAseq was employed to stuudy induction of anegy in hunam T lymphocytes. Anergy is a condition of immune T cells becoming sustainably inactive. Theoretically, it occurs when a T cell recognizes its antigen but cannot be active. Induction of anergy by single amino acid mutated antigen has been shown in mouse models decades ago. The present study applied this method to human cells in vitro, and demonstrated induction of annergy in human T lymphocytes.

overall_design: HLA-A24-positive healthy donor derived PBMC was cultured with (A24-3) or without (A24-1) single amino acid mutated CMV-antigen (QYDPVSALF) for 24hrs, followed by culture in the presence of the original CMV-antigen (QYDPVAALF) for two weeks.


title: Effect of ablating DGCR8 expression on steady state RNA levels in embryonic teratocarcinoma PA-1 cells

city: Edinburgh

first: Alasdair

last: Ivens

address: Kings Buildings

institute: Centre for Immunity, Infection and Evolution

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

overall_design: Refer to individual Series


title: Effect of ablating DGCR8 expression on steady state RNA levels in embryonic teratocarcinoma PA-1 cells [RNA-Seq]

summary: In this dataset we use total RNA-seq to study the effect of DGCR8 absence (knockout) on steady state RNA levels

overall_design: Comparison between RNA samples from wildtype and DGCR8 KO PA-1 cells (WT samples from total RNA-seq were deposited at GSE197472)

first: Lisanne

middle: I

last: Knol

first: Sara

last: Macias


title: Effect of ablating DGCR8 expression on steady state RNA levels in embryonic teratocarcinoma PA-1 cells [miRNA-Seq]

summary: Small RNA sequencing analysis to study the effect of DGCR8 absence (knockout) on miRNA levels

overall_design: Comparison between RNA samples from wildtype and DGCR8 KO PA-1 cells (WT samples from small RNA seq were deposited at GSE197470)


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

city: Rochester

first: Alexander

middle: Quinn

last: Wixom

state: MN

address: 200 1st St SW

department: Quantitative Health Sciences

institute: Mayo Clinic

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

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

first: Yunjung

last: Jin

middle: Q

last: Zhao


title: Long-distance transport of siRNAs with functional roles in pollen development [BiSulfite-seq]

city: Uppsala

first: Juan

middle: C

last: Santos-González

state: Uppsala

address: Almas Allé 5

department: Department of Plant Biology and Forest Genetics

country: Sweden

institute: SLU

type: Methylation profiling by high throughput sequencing

summary: Small interfering RNAs (siRNAs) play a crucial role in plant reproduction, yet their mobility and function remain incompletely understood. We report that a large proportion of siRNAs found in pollen of Capsella rubella relies on mobile siRNAs from maternal sporophytic tissues, highlighting the importance of non-cell-autonomous siRNAs in male gametophyte development. Unlike tapetal siRNAs, which guide DNA methylation and require CLASSY3 and DNA-dependent RNA polymerase IV (Pol IV) activity in the tapetum, we found that Pol IV-dependent mobile siRNAs (PMsiRNAs) mainly function post-transcriptionally and do not guide DNA methylation. Nevertheless, PMsiRNAs share key features with tapetal siRNAs, including Pol IV dependency, clustering and a size range of 21–24 nucleotides. Using a grafting approach, we show that sporophytic Pol IV-dependent siRNAs act as non-cell-autonomous mobile signals that trigger PMsiRNA formation through post-transcriptional gene silencing. This process parallels reproductive phased siRNA biogenesis, which is widespread across angiosperms but has been considered absent in Brassicaceae. Loss of PMsiRNAs causes pollen arrest, underscoring their essential role. Together, these findings highlight siRNAs as long-distance communication signals from maternal sporophytic tissues to the male gametophyte with critical functions in developmental regulation.

overall_design: Hypocotyl grafting was conducted 3 days after germination. The BS-Seq libraries were prepared from DNA of different tissues: pollen, microspores, leaves of grafted plants, and seedling leaves from the progeny of grafted plants. Two biological replicates were used for each genotype.

first: Jiali

last: Zhu

first: Zhenxing

last: Wang

first: Tinja

last: Strothans

first: Thales

last: Cherubino Ribeiro

first: Ai

last: Zhang

first: Charles

last: Melnyk

first: Blake

last: Meyers

first: Claudia

last: Köhler


title: Convergence of aging- and rejuvenation-related epigenetic alterations on PRC2 targets [ChIP-Seq]

city: Baltimore

first: Andrew

middle: Paul

last: Feinberg

state: Maryland

address: 855 N. Wolfe Street

department: Center for Epigenetics

institute: Johns Hopkins University

summary: Rejuvenation of tissues in physiologically aging mice can be accomplished by long-term partial reprogramming via expression of reprogramming factors (Oct4, Sox2, Klf4 and c-Myc). To investigate the epigenetic determinants of partial reprogramming-mediated rejuvenation, we used whole genome bisulfite sequencing to carry out unbiased comprehensive profiling of DNA methylation changes in skin from mice subjected to partial reprogramming, as well as young and untreated old controls. We found a striking convergence of age- and rejuvenation-related epigenetic alterations on targets of the Polycomb repressive complex 2 (PRC2). These results are also supported by a likewise prominent enrichment of PRC2 targets in gene expression data, suggesting that PRC2 activity can modulate aging and mediate tissue rejuvenation.

overall_design: ChIP-Seq for H3K27me3 and H3K9me2 histone marks in isolated epidermis from tail skin collected from old (22 months) and young (3 months) C57BL/6 mice.

first: Oscar

last: Camacho

first: Michael A.

last: Koldobskiy

first: Andrew P.


title: Convergence of aging- and rejuvenation-related epigenetic alterations on PRC2 targets


title: The effects of ATP and CD39 inhibition in monocyte-derived dendritic cells.

city: Hayward

first: Soonweng

last: Cho

state: CA

address: 3928 Point Eden Way

institute: Arcus Biosciences

summary: Extracellular ATP (eATP) is a damage associated molecular pattern (DAMP) that may be released by cancer cells as a result of chemotherapy-induced immunogenic cell death (ICD). We have demonstrated that preserving extracellular ATP (eATP) by inhibiting the extracellular ATPase CD39 boosts anti-tumor immunity in various models. We recently reported the development of AB598, a very specific and potent therapeutic antibody that inhibits CD39 enzymatic activity. We demonstrated using a cancer cell-moDC co-culture system that chemotherapy-induced ATP release with AB598 inhibition is sufficient to activate moDCs to a greater antigen presenting cell (APC) phenotype. Using this co-culture system, we generated and tested an ATP signature that shows promising utility in tumor biopsies.

overall_design: RNAseq of monocyte-derived dendritic cells (moDCs) in various co-culture conditions including combinations of A549 cells, docetaxel, AB598 or isotype control, or ATP. Viable moDCs were sorted out from A549 cells using positive selection for CD11c.

first: Rebecca

last: Fuchs

first: Ke

first: Christine

last: Bowman

first: Jenna

middle: L

last: Pappalardo


title: Long-distance transport of siRNAs with functional roles in pollen development [RNA-seq]

first: Juan

overall_design: Each RNA-Seq library was prepared from microspores of grafted plants. 3 grams of flower tissue were used for microspore extraction. Two biological replicates were used for each genotype.

first: Jiali


title: Cup-like nuclei is a hallmark of IGH:DUX4 acute lymphoblastic leukemia and reveals cytoplasmic mitochondria accumulation

city: Paris

first: Hélène

last: CAVE

state: France

address: 48 Bd sérurier

department: Genetics

country: France

institute: APHP Hôpital Robert Debré

summary: Cup-like nuclei are a distinctive morphological feature observed in certain cases of acute lymphoblastic leukemia (ALL). We provide evidence that they characterize DUX4-rearranged ALL independently of IKZF1 deletion, and reveal marked mitochondrial accumulation in this ALL subset. We provide here the RNAseq data from DUX4 rearranged ALL and non-DUX4 rearranged ALL which revealed DUX4-rearranged distinct transcriptional mitochondrial signature.

overall_design: RNAseq data on mononucleated cells from 19 DUX4r and 67 non-DUX4r pediatric ALL cases

first: Chloé

last: Arfeuille

first: Hugo

last: Roux

first: Yoann

last: Vial

first: Aurélie

last: Caye

last: Cavé

first: Marion

last: Strullu

first: Alexia

last: Kinoo


title: mRNAseq profiling of hCoV229E infected A549 cells

city: Braunschweig

first: Fakhar

last: Waqas

address: Inhoffenstr

institute: Helmholtz Zentrum für Infektionsforshcung GmbH

summary: A549 cells are infected with hCoV229E and treated with Bardoxolone, 4-octyl itaconate and Selinexor in order to understand the antiviral mechanism of these treatments

overall_design: A549 cells were infected with hCoV229E for 4 hours and treated with compounds and samples were collected after 24 and 48 h. p.i.

first: Frank

last: Pessler

first: Robert

last: Geffers


title: Astrocytic FKBP5 regulates neuroinflammation and cognitive outcomes in male mouse models of excitotoxic epilepsy

city: Taipei City

first: Yu-Ling

last: Gan

address: No. 155, Sec. 2, Linong St. Beitou Dist.

department: Department and Institute of Physiology

country: Taiwan

institute: National Yang Ming Chiao Tung University

summary: FK506-binding protein 51 (FKBP51, encoded by FKBP5) is a multisignaling cochaperone that regulates cellular stress responses and inflammatory signaling through the NF-κB pathway. Although FKBP51 is upregulated in reactive astrocytes, its role in epilepsy and excitotoxic neuroinflammation remains unknown. Excessive astrogliosis and impaired glutamate transporter-1 (GLT-1)-mediated glutamate clearance promote excitotoxicity and increase seizure susceptibility. Here, we investigated how both global and astrocyte-specific Fkbp5 deletions influence seizure susceptibility, astrogliosis, neuroinflammation, and cognition in male mice subjected to a kainic acid (KA)-induced epilepsy mouse model. Global Fkbp5 knockout (Fkbp5-KO) presented lower seizure activity along with decreased neuronal loss and astrogliosis in the hippocampus compared with the wild-type mice. Astrocyte-specific Fkbp5 conditional knockout (aFkbp5-cKO) mice similarly attenuated seizure severity, decreased astrogliosis, improved novel object recognition, and preserved GLT-1 expression in hippocampal CA3. Glia-neuron mixed cultures derived from Fkbp5-KO brains showed reduced NMDA-induced neurotoxicity and astrogliosis, accompanied by decreased NF-κB p65 phosphorylation. Notably, overexpression of an Fkbp5 quadruple mutant that disrupts the FKBP51-NF-κB interaction inhibited proinflammatory lipopolysaccharide-induced astrogliosis and NF-κB activation. Transcriptomic analysis of Fkbp5-KO hippocampi further confirmed suppression of NF-κB-driven inflammatory pathways. In summary, astrocytic FKBP51 mediates reactive astrogliosis and GLT-1 downregulation, linking excitotoxic neuroinflammation with seizure susceptibility and cognitive impairment, and represents a potential intervention target for epilepsy.

overall_design: RNA-seq was performed on hippocampal tissues from 12-week-old male wild-type and Fkbp5 knockout mice 7 days after a single intraperitoneal injection of either saline or 3 mg/kg lipopolysaccharide.

first: Wei-Hsuan

last: Huang

first: Pin-Hua

last: Sung

first: Chung-Jiuan

last: Jeng

first: Yi-Hsuan

last: Lee


title: Development of a single domain antibody to target a G-quadruplex located on the hepatitis B virus covalently closed circular DNA Genome

city: Lethbridge

first: Trushar

last: Patel

state: Alberta

address: Science Commons

department: chemistry and Biochemistry

country: Canada

institute: university of lethbridge

summary: Guanine-quadruplexes (G4s) are a secondary structure that can be adopted by DNA and have recently been shown to play an important role in regulating viral replication, transcription, and translation. Here we describe the development of a humanized single-domain antibody (S10) that can target a G4 located in the PreCore/Core (PreC) promoter region on the hepatitis B virus (HBV) covalently closed circular DNA (cccDNA) genome. Using cross-linking chromatin immunoprecipitation (ChIP) coupled with qPCR and next-generation sequencing, we show that S10 binds to HBV’s PreC locus and cccDNA, showing target specificity. Herein, we demonstrate that a single domain antibody can be designed to probe the existence of a G4 in vitro and intracellularly within the HBV cccDNA genome.

overall_design: Chromatin Immunoprecipitation DNA-sequencing (ChIP-seq) to understand binding distribution for HBcAg, Sp1, S10-HA, S1-HA, H3K27Ac on hepatitis B virus genome.

first: Carla

middle: S

last: Coffin


title: Long-distance transport of siRNAs with functional roles in pollen development [sRNA-seq]

first: Juan

last: Santos-González

overall_design: Anther samples were collected after dissecting flowers and for RNA extraction, endosperm was manually dissected from seeds 6~7 days after pollination. Two biological replicates were used for anther, pollen, and endosperm samples, three biological replicates were used for root samples

first: Jiali

last: Zhu

first: Zhenxing

last: Wang

first: Tinja

last: Strothans

first: Thales

last: Cherubino Ribeiro

first: Ai

last: Zhang

first: Charles

last: Melnyk

first: Blake

last: Meyers

first: Claudia

last: Köhler


title: A Comprehensive Proteogenomic and Spatial Analysis of Innate and Acquired Resistance of Metastatic Melanoma to Immune Checkpoint Blockade Therapies

city: Philadelphia

first: Yeqing

last: Chen

address: 3601 Spruce Street

institute: The Wistar Institute

summary: While a subset of patients with metastatic melanoma achieves durable responses to immune checkpoint blockade (ICB) therapies, the majority ultimately exhibit either innate or acquired resistance to these treatments. However, the molecular mechanisms underlying resistance to ICB therapies remain elusive and are warranted to elucidate. Here, we comprehensively investigated the tumor and tumor immune microenvironment (TIME) of paired pre- and post-treatment tumor specimens from metastatic melanoma patients who were primary or secondary resistance to anti-CTLA-4 and/or anti-PD-1/PD-L1 therapies. Differentially expressed gene (DEG) analysis and single-sample gene set enrichment analysis (ssGSEA) with transcriptomic data identified cell cycle and c-MYC signaling as pathway-based resistance signatures. And weighted gene co-expression network analysis (WGCNA) revealed the activation of a cross-resistance meta-program involving key signaling pathways related to tumor progression in ICB resistant melanoma. Moreover, spatially-resolved, image-based immune monitoring analysis by using NanoString’s digital spatial profiling (DSP) and Cyclic Immunofluorescence (CyCIF) showed infiltration of suppressive immune cells in the tumor microenvironment of melanoma with resistance to ICB therapies. Our study reveals the molecular mechanisms underlying resistance to ICB therapies in patients with metastatic melanoma by conducting such integrated analyses of multi-dimensional data, and provides rationale for salvage therapies that will potentially overcome resistance to ICB therapies.

overall_design: To reveal the transcriptomic landscape of innate and acquired resistance to ICB therapies in patients with metastatic melanoma. We represent this cohort of RNAseq for patient-matched paired pre- and post- treatment tumor specimens from patients treated with ICB therapies.

first: Shiyou

last: wei

first: Kuang

last: Du

first: Hongbin

last: Lan

first: Zhenyu

last: Yang

first: Yulan

last: Deng

first: Zhi

last: Wek

first: Dennie

last: T Frederick

first: Jinho

first: Marilyne

last: Labrie

first: Tian

last: Tian

first: Tabea

last: Moll

first: Ryan

last: J Sullivan

first: Gordon

last: Mills

first: Genevieve

last: M Boland

first: Keith

last: T Flaherty

first: Lunxu

last: Liu

first: Meenhard

last: Herlyn

first: Gao


title: Genome-wide chromatin interaction profiling with Hi-C following VPA treatment in HEK293 cells

city: Tokyo

first: Yutaka

last: Saito

department: Artificial Intelligence Research Center (AIRC)

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

summary: Valproic acid (VPA), a histone deacetylase (HDAC) inhibitor induces epigenetic changes through histone hyperacetylation which lead to chromatin remodeling, including the alteration of compartments, TAD boundaries and chromatin loops. To determine the effects of VPA on 3D chromatin organization, we performed Hi-C sequencing on untreated and VPA-treated HEK293T cells. VPA treatment results in increased A compartments which represents regions associated with active transcription, with more switching from B-to-A compartments. In VPA-treated HEK293T cells, reduced TAD boundaries and increased chromatin loops were also observed, which supports the evidence of active transcription triggered upon histone hyperacetylation induced by VPA.

overall_design: We performed Hi-C on untreated and VPA-treated HEK293T cells. Differential analysis was performed to elucidate the genomic changes triggered by VPA.

first: Yicheng

last: Wang

first: Nur

last: Ab Ghani

first: Munmee

last: Dutta

first: Shungo

last: Adachi

first: Kaoru

last: Katoh

first: Masakazu

last: Namihira

first: Toutai

last: Mitsuyama


title: Genome-wide gene expression profiling with RNA-seq following VPA treatment in HEK293 cells

summary: Valproic acid (VPA), a histone deacetylase (HDAC) inhibitor induces epigenetic changes through histone hyperacetylation which could affect gene expression. To determine the effects of VPA on gene expression changes, we performed RNA-seq on untreated and VPA-treated HEK293T cells. Differentially-expressed genes (DEGs) induced by VPA exposure were enriched in signaling processes, regulation of ion transport and extracellular matrix organization, known to be associated with HDAC activities.

overall_design: We performed RNA-seq in HEK293T cells. The experiments were performed in triplicates. Gene count and differential RNA-seq peak analysis was performed to identify differentially expressed genes (DEGs). DEGs were further used for Gene Ontology and KEGG pathway analysis.

first: Wang

last: Yicheng

first: Ab

last: Nur Syatila

first: Dutta

last: Munmee

first: Adachi

last: Shungo

first: Katoh

last: Kaoru

first: Namihira

last: Masakazu

first: Mitsuyama

last: Toutai

first: Saito

last: Yutaka


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

city: Fuzhou

first: Sun

last: Minghui

address: Cangshan

institute: Fujian Agriculture and Forestry University

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

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

first: Minghui

last: Sun

first: Zhenhong

last: Zhuang


title: singlecell RNA sequencing of lung transplanted mice

city: Chicago

first: Yudai

last: Miyashita

state: IL

address: Simpson Querrey 5-402-C 303 E Superior Street

department: Thoracic Surgery

institute: Northwestern Univesity

summary: This dataset contains single-cell RNA sequencing (scRNA-seq) data from murine lung transplantation models. The study investigates the expression of fibroblast activation protein (FAP) as an early biomarker in chronic lung allograft dysfunction (CLAD). Lung samples were collected at baseline, day 7, and day 28 post-transplantation to analyze gene expression patterns associated with fibrotic remodeling. This dataset provides insights into the cellular heterogeneity and dynamic changes occurring in lung allografts during CLAD progression.

overall_design: C57BL/6 mouse lungs were orthotopically transplanted into C57BL/10 recipients. Lung tissues were harvested at three time points: baseline (resting), day 7, and day 28 post-transplantation. Single-cell suspensions were prepared and processed using the 10x Genomics platform. Raw sequencing data were processed using Cell Ranger, and subsequent data analysis was performed with Seurat for clustering, UMAP visualization, and differential gene expression analysis. This experimental design allows for temporal assessment of gene expression changes during CLAD development.

first: Taisuke

last: Kaihou

first: Hideki

last: Nagata

first: Takashi

last: Hiroshima

first: Yusuke

last: Sugiura

first: Kaijie

last: Zhang

first: Yuangqing

last: Yan

first: Alicia

last: Steffens

last: Kanou

first: Toru

last: Kimura

first: Bowen

last: Wang

first: Ankit

last: Bharat

first: Yasushi

last: Shintani

first: Chitaru

last: Kurihara


title: Mouse lung tissue RNA-Seq from C57Bl6 wild type and ALOX15 KO mice with and without house dust mite (HDM) exposure.

city: Thousand Oaks

first: Jonathan

last: Phillips

address: 1 Amgen center drive

institute: Amgen

summary: Purpose: Identify genes disregulated in wild type C57Bl6 mouse lung tissue in the house dust mite (HDM) asthma disease model and genes differentially expressed in ALOX15 KO mice.

overall_design: C57Bl6 mice were challenged daily for 14 days with intranasal house dust mite (HDM) extract.  The HDM challenged mouse lung RNA-Seq from wild type mice was compared to RNA-Seq from lungs of ALOX15 knock out mice.


title: Convergence of aging- and rejuvenation-related epigenetic alterations on PRC2 targets [WGBS]

first: Andrew

last: Feinberg

overall_design: WGBS on dorsal skin and isolated tail epidermis samples from five mice treated with long-term partial reprogramming from 15 months of age until 22 months, untreated mice (22 months), and young (3 months) mice.

first: Oscar

last: Camacho

first: Michael

middle: A

last: Koldobskiy

middle: P


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

first: Sun

last: Minghui

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

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

first: Minghui

last: Sun

first: Zhenhong

last: Zhuang


title: Plasma miRNA as potential biomarkers for Alzheimer's Disease

city: Kuala Lumpur

first: Siow-Wee

last: Chang

address: Faculty of Science

country: Malaysia

institute: Universiti Malaya

summary: The deregulation of microRNA (miRNA) might be potential biomarkers for Alzheimer's Disease (AD). In this study, we aim to investigate the miRNA profiles of AD in Malaysian AD patients. Small RNA sequencing was performed in order to obtain the miRNA profiles from the peripheral plasma of AD patients and normal controls.  Differential expression analysis was performed to identify the dysregulated miRNAs. Three miRNAs that are relevant with AD were identified. The functions of these miRNAs were found to be related with oxidative phosphorylation, mitochondrial dysfunction and calcium-mediated signalling, which contributed to AD pathogenesis. This study supports evidence that the miRNA expression changes in AD and indicates the need for further study in this area.

overall_design:
Small RNA sequencing was performed on 7 AD patient and 4 normal control. The miRNA profiles was extracted using NEXTflex Illumina Small RNA Sequencing Kit v3.

Grant ID: FRGS/1/2019/SKK06/UM/02/5
Grant Title: A Machine Learning Integrated Framework for Investigating Potential Biomarkers in Alzheimer's Disease
Funding source: Fundamental Research Grant Scheme (FRGS), Ministry of Higher Education Malaysia.

first: Mei-Sze

last: Tan

first: Phaik-Leng

last: Cheah

first: Ai-Vyrn

last: Chin

first: Lai-Meng

last: Looi


title: Loss of Serpin E2 alters antimicrobial gene expression by microglia but not astrocytes

city: Los Angeles

first: Ye

last: Zhang

address: 635 Charles E Young Dr S

institute: UCLA

summary: To investigate the influence of Serpin E2 (aka PN-1) on glia in the brain, we purified microglia and astrocytes and performed RNA sequencing from Serpine2-/- mice

overall_design: Microglia or astrocytes were purified from the brain of adult Serpine2-/- mice and littermates with at least one functional Serpine2 allele. Half of the sibling pairs were injected with lipopolysaccharides and others received saline injections.

first: Mitchell

last: Krawczyk

first: Marlesa

last: Godoy

first: Paul

last: Vander

first: Alice

middle: J


title: Genome-wide profiling of histone modification H3K27ac and CTCF transcription factor binding following VPA treatment in HEK293 cells

first: Yutaka

last: Saito

summary: Valproic acid (VPA), a histone deacetylase (HDAC) inhibitor induces epigenetic changes through histone hyperacetylation which lead to alteration to H3K27ac and CTCF binding in the genome. To determine the effects of VPA on 3D chromatin organization, we performed ChIP-seq  on untreated and VPA-treated HEK293T cells. VPA treatment results in elevated H3K27ac marks and slightly reduced CTCF binding, which supports the evidence of active transcription triggered upon histone hyperacetylation induced by VPA.

overall_design: We performed chromatin immunoprecipitation DNA-sequencing (ChIP-seq) for histone modification H3K27ac and transcription factor CCCTC-binding factor (CTCF) in both untreated and VPA-treated HEK293T cells. The experiments were performed in triplicates. Peak calling and differential ChIP-seq peak analysis was performed to elucidate the genomic changes triggered by VPA.

first: Wang

last: Yicheng

first: Ab

last: Nur Syatila

first: Dutta

last: Munmee

first: Adachi

last: Shungo

first: Katoh

last: Kaoru

first: Namihira

last: Masakazu

first: Mitsuyama

last: Toutai

first: Saito

last: Yutaka


title: Sex differences in Yap1 oncogene function in immune evasion [scRNA-seq]

city: Houston

first: Nourhan

last: Abdelfattah

state: TX

address: 6670 Bertner Avenue

institute: Houston Methodist Research Institute

summary: The incidence of many human cancers differs according to sex, but little is known about the interplay between oncogenic events and sex as a variable in tumorigenesis. Here we report that the oncogene Yap1 is sexually dimorphic in medulloblastoma progression and immune suppression. We show that Yap1 promotes stemness and blocks differentiation in sonic hedgehog (SHH)-subtype medulloblastoma by at least two distinct but complementary molecular mechanisms to regulate the RNA expression and protein functions of Sox2, Atoh1, NeuroD1, and Zic1/2. Yap1 also promotes an immune suppressive tumor microenvironment by directly regulating Csf1, Igf1, and Igfbp3 transcription and modulating IL6-JAK-STAT3, TNFR1, TGF-β, and CCL5 immune pathways. Notably, Yap1 function is more critical in males and this is evolutionarily conserved: genes downstream of YAP1 identified in mouse models stratify male but not female medulloblastoma patient survival. In summary, we demonstrate a sex-based function for an oncogene, underscoring the critical need to incorporate sex as a variable in cancer mechanism and clinical response studies, particularly those involving YAP1

overall_design: Comparative scRNA-seq data for fSMO-M2;hGFAPcre (SG)  and rescued  fYap1;fSMO-M2;hGFAPcre (YSGr) males and females at end point

first: Kyuson

last: Yun


title: Sex differences in Yap1 oncogene function in immune evasion [P8_Bulk RNA-seq]

overall_design: Comparative gene expression profiling analysis of RNA-seq data for fSMO-M2;hGFAPcre (SG), non rescured   fYap1;fSMO-M2;hGFAPcre (YSGnr)  and rescued  fYap1;fSMO-M2;hGFAPcre (YSGr) at P8/P9 after birth


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

city: Boston

first: Amy

last: Huang

state: MA

address: 25 Shattuck St

department: Immunology

institute: Harvard Medical School

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

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

first: Matt

last: Zimmerman

first: Megan

last: Fung

first: Emily

last: Cox

first: Wan

last: Chong

first: Katherine

last: Vietor

first: Yacine

last: Choutri

first: Rose

last: Al Abosy

first: Nicholas

last: Haining

first: Debattama

last: Sen

first: Arlene

last: Sharpe

first: Brian

last: Miller


title: Sex differences in Yap1 oncogene function in immune evasion [ChIP-seq]

overall_design: YAP1 ChIPseq data from male and female  fSMO-M2;hGFAPcre (SG) tumors


title: Spatiotemporal transcriptome atlas of ovule development in gymnosperms reveals co-regulatory patterns of gene expression associated with polarity establishment

city: Shanghai

first: Tao

last: Jin

address: Handan Rd. 220

institute: Fudan University

summary: Ovule, as the precursor to seed, represents a key evolutionary innovation in seed plants, enhancing their adaptability and biodiversity. Researches in model angiosperms have revealed that ovule development involves the establishment of polarity, which drives cell differentiation and organ formation. However, studies on gymnosperms have primarily focused on morphological comparisons and limited gene function analyses, leaving the core regulatory networks underlying ovule organogenesis in the common ancestor of seed plants a subject of ongoing debate. We employed spatial transcriptome sequencing to dissect the dynamic gene expression profiles across various tissues during early ovule development in four representative gymnosperm species: Ginkgo biloba, Gnetum montanum, Pinus tabulaeformis and Cycas panzhihuaensis. The analyses reveal distinct trajectories of cell types during formation of tissues, uncovering critical genes and pathways involved in the initiation and differentiation of ovule primordium, as well as the subsequent formation of chalaza, integument and nucellus. The spatial and temporal expression patterns of key regulatory genes, particularly those associated with proximal-distal polarity establishment, strongly support the hypothesis that early-formed chalaza regions constitute the meristematic cells, giving rise to the formation of integument and nucellus. Furthermore, specific gene expression patterns in the developing integument exhibit clear adaxial-abaxial distribution, offering clues for understanding the molecular mechanisms driving integument formation. The spatial transcriptome analyses in this study provide a detailed landscape of gene activity during ovule organogenesis in multiple gymnosperms, and offer valuable resources for future genomic and evolutionary studies on seed development.

sample_organism:
Ginkgo biloba
Gnetum montanum
Pinus tabuliformis
Cycas panzhihuaensis

overall_design: We performed spatial transcriptome sequencing on ovule tissues from four representative gymnosperms species, Ginkgo biloba, Gnetum montanum, Pinus tabuliformis and Cycas panzhihuaensis, covering most of major gymnosperms clades . The dataset comprises over fifty samples spanning multiple developmental stages, from the presence of meristematic regions to near-mature organs, included in ten slides.

first: Min

last: Jiang

first: Ji

last: Qi

last: Yang


title: Sex differences in Yap1 oncogene function in immune evasion

first: Nourhan

last: Abdelfattah

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

overall_design: Refer to individual Series


title: single cell RNA-seq of mice synovium

city: Bunkyo-ku, Tokyo

first: Hisatoshi

last: Ishikura

state: Japan

department: Orthopaedic

institute: University of Tokyo

summary:
Purpose: Joint function is impaired by disuse. We investigated mice synovium for control and MMS(minimized mechanical stress) model mice.
Method: We developed a MMS model which could represent the disused joint by combining non-weight bearing with tail suspension and knee joint immobilization with a plastic cylinder. We  obtained synovial cells from control and MMS day14 mice.
Conclusion: Specific subsets in MMS synovium expressed many secreted proinflammatory cytokines and are thought to be the tragger of cartilage degeneration..

overall_design: single cell RNA-seq of synovium in control and MMS model mice

first: Taku

last: Saito


title: Bulk RNA-seq of mice synovium

summary:
Purpose: Joint function is impaired by disuse. We investigated mice synovium and cartilage for control and MMS (minimized mechanical stress) model mice.
Method: We developed a MMS model which could represent the disused joint by combining non-weight bearing with tail suspension and knee joint immobilization with a plastic cylinder. We followed the time course of MMS model for day 3,7,14 for synovium and day 3,7,14,28 for cartilage. In addition, we used two models to stop the immobilization; in R1, only the joint immobilization was canceled at 2 weeks, but tail suspension was continued; in R2, both the joint motion and weight bearing were allowed at 2 weeks.
Conclusion: MMS synovium expressed many secreted proinflammatory cytokines. MMS cartilage expressed less cartilage anabolic genes.

overall_design: mRNA of synovium and cartilage in control and MMS model mice


title: Sex differences in Yap1 oncogene function in immune evasion [EndPoint_Bulk RNA-seq]

overall_design: Comparative gene expression profiling analysis of RNA-seq data for fSMO-M2;hGFAPcre (SG)  and rescued  fYap1;fSMO-M2;hGFAPcre (YSGr) at end point

first: Kyuson

last: Yun


title: High-dimensional analysis of single neurosphere molecular states reveals an ethanol-mediated shift in distribution along maturation trajectories

city: Albuquerque

first: Rajanikanth

last: Vadigepalli

state: PA

address: 1 University of New Mexico

institute: University of New Mexico

summary: The fetal cerebral cortical neuroepithelium is a clonal mosaic, wherein populations of neural stem and daughter progenitor cells cycle asynchronously between multiple molecular states to generate cortical plate neurons. We hypothesized that these molecular states within neuroepithelial clonal colonies may be perturbed by fetal teratogens like alcohol, and that analyses of these perturbations may yield clues about mechanisms underlying teratogenesis. Fetal mouse dorsal telencephalon was microdissected at gestational day (GD) 12.5, dispersed single cells cultured for 5 days to yield clonal neurosphere cell aggregates, in either defined control culture media, or with a dose-range of ethanol. We assessed 68 gene transcripts by multiplexed RT-PCR in 264 individual neurospheres, across all treatment conditions. Cluster analysis resulted in the classification of control neurospheres into seven separate categories along a developmental trajectory from neuroepithelial, to transit-amplifying, to neuronal identity. Moreover, smaller control neurospheres were more immature than larger neurospheres. Ethanol exposure resulted in dose-related dissociation between neurosphere size and maturation state, with smaller neurospheres biased towards later maturation states. This pro-maturation effect was particularly pronounced at the highest doses of ethanol. These data suggest that ethanol facilitates neuroepithelial maturation with concurrent loss of stem cells, which may contribute to diminished brain growth.

overall_design: A total of 400 neurospheres were collected from 2 independent culture sets (Set-A and Set-B, 200 per set). Each set included 50 neurospheres from each control (0mM EtOH) and ethanol treatment conditions (25, 75 and 100mM EtOH). Each neurosphere was imaged prior to collection and 264 neurospheres processed individually for RT-qPCR using the Biomark HD system (protocol ADP 42), for mRNA expression across 96 genes in three separate runs at 88 neurospheres per run.

first: Sirisha

last: Achanta

first: Aalap

last: Verma

first: Rajesh

last: Miranda


title: Integrative epigenomic profiling of VPA treatment in HEK293 cells

first: Yutaka


title: Balb/c mouse lung tissue RNA-Seq in mouse OVA asthma model with and without anti-mouse-IL-4Ra antibody treatment.

first: Jonathan

last: Phillips

summary: Purpose: Identify genes disregulated in Balb mouse lung tissue in the Ovalbumin (OVA) asthma disease model and genes disregulated by OVA challenged mice treated with with an Anti-mouse-IL-4Ra mAb

overall_design: Balb mice were sensitized to ovalbumin systemically (i.p.) and challenged with nebulized ovalbumin.  The OVA challenged mouse lung RNA-Seq was compared to RNA-Seq from lungs of mice sham (Saline) sensitized or treated with 30 mg/kg of an anti-mouse-IL-4Ra mAb


title: Small RNA Profiles in Soybean Pol IV and V Mutants

city: Riverside

first: Brandon

last: Le

address: 3401 Watkins Drive

department: Institute for Integrative Genome Biology

institute: University of California, Riverside

summary: We profiled the small RNA-ome, transcriptome, and DNA methylome of RNAi lines to study the molecular and biological functions of Pol IV and V in soybean.

overall_design: Three, six, and six transgenic and non-transgenic siblings for GmNRPD1, GmNRP(D/E)2, and GmNRPE1, respectively, were obtained for this study.

middle: H

first: Xuemei

last: Chen


title: Soybean Pol IV and V Mutants


title: Molecular Heterogeneity and Immune Infiltration Drive Clinical Outcomes in Upper Tract Urothelial Carcinoma

status: Public on Feb 01 2026

city: New York

first: Fengshen

last: Kuo

state: New York

address: 1275 York Ave

institute: Memorial Sloan Kettering Cancer Center

summary: Molecular classification of upper tract urothelial carcinoma (UTUC) can provide insight into divergent clinical outcomes and provide a biological rationale for clinical decision-making. As such, we performed multi-omic analysis of UTUC tumors to identify molecular features associated with disease recurrence and response to immune checkpoint blockade (ICB). Five molecular clusters with distinct clinical outcomes were identified. Favorable subtypes (C1 and C2) were characterized by a luminal-like signature and an immunologically depleted tumor microenvironment (TME). Subtype C3 was characterized by FGFR3 alterations and a higher tumor mutational burden, and included all tumors with microsatellite instability. Despite higher rates of recurrence and inferior survival, subtypes C4 and C5 harbored an immunologically rich TME favoring response to ICB. Limitations include extrapolation of molecular features of tumors from the primary site to determine response to systemic immunotherapy and the limited resolution of bulk sequencing to distinguish gene expression in the tumor, stroma, and immune compartments. RNA sequencing identified previously underappreciated UTUC molecular heterogeneity and suggests that UTUC patients at the highest risk of metastatic recurrence following surgery include those most likely to benefit from perioperative ICB.

overall_design:
Whole transcriptome RNA sequencing was performed on 100+13 UTUC tumors collected from patients undergoing nephroureterectomy.

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

last: Kim

first: Syed

last: Alam

first: Ziyu

first: Taha

last: Merghoub

first: David

middle: B

last: Solit

last: Coleman


title: Next Generation Sequencing Analysis of Breast Cancer Cell Line MCF-7 And MDA-MB-231 After PI3K Inhibition

city: Shaoxing

first: Xin

last: Xie

address: No. 508, Huancheng West Road, Shaoxing

department: School of life sceince

institute: Shaoxing Univeristy

summary: mRNA profiles of MCF7 and MDA-MBA-231 cells treated with 1μM GDC-0941 or DMSO for 24 hours

overall_design: The goals of this study are to use NGS to perform transcriptome profiling (RNA-seq) to find the changes of the global gene expression programs after PI3K signaling inhibition in MCF-7 and MDA-MB-231 breast cancer cell lines. Cells were treated with  1μM GDC-0941 or DMSO for 24 hours. Total RNA was extracted and submitted for RNA-seq analysis

first: Pu-Ste

last: Liu


title: Transcriptome Profiles in Soybean Pol IV and V Mutants

overall_design: Three, six, and six transgenic (T) and non-transgenic (NT) siblings for GmNRPD1, GmNRP(D/E)2, and GmNRPE1, respectively, were obtained for this study.


title: Dopamine neuron specific RNA-sequencing reveals Neprilysin 1 acts downstream of the cohesin complex to suppress learning

city: Edmonton

first: Anna

last: Phan

state: AB

address: Z-1111 BioSci

department: Bioinformatics and Statistics Core

institute: UF Scripps Biomedical Research

summary: We previously identified Stromalin, a cohesin complex subunit, as a learning suppressor in Drosophila melanogaster that acts by limiting synaptic vesicle numbers in dopamine neurons. However, the mechanism by which Stromalin modulates synaptic vesicles remains unclear. We hypothesized that this occurred through the cohesin complex’s function in developmental gene regulation. Through dopamine neuron-specific RNA-sequencing followed by RNAi screening, we identified Neprilysin 1 (Nep1), a zinc-dependent metallopeptidase, to be positively regulated by the cohesin complex and a key downstream effector of Stromalin. Nep1 knockdown phenocopies Stromalin knockdown effects, enhancing learning and memory and increasing synaptic vesicle markers in dopamine neurons. Like Stromalin, Nep1 suppresses synaptic strength between dopamine and mushroom body neurons. Finally, we show Nep1 overexpression rescues both memory and synaptic vesicle phenotypes caused by Stromalin reduction. Interestingly, while cohesin complex appears to set the expression levels for Nep1 during development, Nep1 function in adult flies supports its learning effects.

overall_design: Dopamine neuron specific RNA-sequencing of WT and Stromalin knockdown neurons

first: Ronald

last: Davis

first: Courtney

last: MacMullen


title: Genome-wide identification and tissue-specific profiling of microRNAs in lentil (Lens culinaris Medik.)

city: Kayseri

first: Saffet

last: Teber

address: Erciyes University Faculty of Agriculture, Köşk Mahallesi, Fuat Sezgin Caddesi No:12, Melikgazi/KAYSERİ

country: Turkey

institute: Erciyes University

summary: MicroRNAs (miRNAs) are key post-transcriptional regulators that influence plant development, metabolism, and stress adaptation. Despite the agronomic importance of lentil (Lens culinaris Medik.), its miRNA landscape remains poorly characterized. This study aimed to establish a comprehensive, tissue-specific atlas of conserved and novel miRNAs to improve understanding of gene regulation in lentil. Small RNA libraries from seven tissues—root, shoot, stem, mature leaf, flower, flower bud, and young pod—were sequenced using the Illumina HiSeq platform, generating over 432 million reads. A total of 1,490 miRNA candidates were identified, comprising 415 conserved and 1,075 novel miRNAs. Among 370 miRNAs with sufficient expression for analysis, 61% showed significant tissue-dependent variation, revealing extensive spatial regulation. Conserved miRNAs such as miR156, miR159, miR164, and miR172 displayed expression patterns consistent with their known developmental roles, whereas most novel miRNAs exhibited tissue-restricted accumulation, particularly in roots and reproductive organs. Predicted target and enrichment analyses indicated that conserved miRNAs primarily regulate transcription factors and hormone signaling components, while novel miRNAs are associated with redox homeostasis, lipid metabolism, and transport processes. This study provides the first comprehensive overview of miRNA expression in lentil, revealing a dual-layer regulatory architecture comprising conserved miRNAs that coordinate core developmental pathways and novel miRNAs that fine-tune tissue-specific and adaptive responses. The expanded lentil miRNA repertoire established here represents a valuable resource for future studies in legumes, including functional, evolutionary, and breeding-related applications.

overall_design: miRNA expression profiling in lentil tissues (from seven tissues—root, shoot, stem, mature leaf, flower, flower bud, and young pod) using high-throughput sequencing.

first: Melike

last: Bakir

first: Ozge

last: Doganay

first: Hamdi

last: Ozaktan

first: Tolga

last: Can

first: Abdullah

last: Kahriman

first: Eric Bishop

last: von Wettberg


title: Neddylation inhibition extends lifespan and preserves cardiac function during aging via mitophagy

city: Columbus

first: Gang

last: Xin

address: 460 W 12th Ave

department: MI&I

institute: The Ohio State University

summary: Age-related cardiac dysfunction is closely linked to impaired mitophagy and mitochondrial quality control. Here, we identify neddylation inhibition as a previously unrecognized strategy to activate mitophagy and improve cardiac function during aging. Using high-content screening of ~10,000 compounds, we uncovered MLN4924, a clinically advanced neddylation inhibitor, as a potent inducer of mitophagy across diverse systems. MLN4924 enhanced mitophagic flux in human iPSC-derived cardiomyocytes and mouse hearts via a non-canonical pathway that bypasses PINK1/Parkin and mitochondrial fission. Mechanistically, MLN4924 stabilized HIF1α by disrupting CUL2-mediated degradation, leading to upregulation of the mitophagy receptor BNIP3. In aged mice, late-life MLN4924 treatment restored cardiac mitophagy, reversed ventricular hypertrophy, and improved diastolic function. MLN4924 also extended lifespan in C. elegans, underscoring the systemic benefit of neddylation blockade. These findings establish neddylation as a druggable regulator of mitochondrial quality control and aging, offering a potential therapeutic framework to combat age-related cardiac decline.

overall_design: Transcriptomic profiling of cardiac tissue of young and aged mice treated with vehicle, and aged mice treated with MLN4924

first: Barta

last: Hayley

first: Chen

last: Kangxuan

first: Gorr

last: Matthew

first: Xia

last: Menghang

first: Zhang

last: Li

first: Chaudhuri

last: Samhita

first: Jin

last: Jiacheng

first: Xu

last: Xianyao

last: Gang

first: Hund

last: Thomas

first: Wold

last: Loren

first: Finkel

last: Toren

first: Sun

last: Nuo


title: Lung gene expression in WT and estrogen receptor alpha and beta knockout mice exposed to house dust mites

city: Bloomington

first: Patricia

last: Silveyra

email: psilveyr@iu.edu, ptrcslvr@gmail.com

state: Indiana

department: Environmental and Occupational Health

institute: Indiana University Bloomington

summary: Sex differences in asthma severity suggest that estrogen signaling plays a key regulatory role in airway inflammation and remodeling, yet the specific contribution of estrogen receptors (ERα and ERβ) remains poorly defined. Here, we investigated how ERα and ERβ shapes physiological, structural, and immunological responses to chronic allergen exposure by examining wild-type (WT), ERα knockout (Esr1⁻/⁻) and ERβ knockout (Esr2⁻/⁻) male and female mice subjected to 5-weeks of house dust mite (HDM) challenge.

overall_design: RNAseq profiling of whole lung tissue from WT, Esr1 knockout and Esr2 knockout mice exposed to house dust mites or PBS for 5 weeks

first: Carolyn

middle: D

last: Ekpruke


title: CSN3 promotes gastric cancer invasion and is associated with immune infiltration via activating NOD/TLR pathways

city: Guiyang City

first: Haiyan

last: Wang

state: Guizhou

address: No. 9, Beijing Road, Yunyan District,

institute: Guizhou Meidical University

summary: We found that CSN3 is highly expressed in gastric cancer and is associated with advanced tumor stage, lymph node metastasis, and poor prognosis. Functional assays showed that CSN3 promotes proliferation and migration while inhibiting apoptosis in GC cells. RNA-sequencing revealed that CSN3 overexpression predominantly activates innate immune–related pathways, particularly the NOD-like receptor and Toll-like receptor signaling pathways, suggesting a role for CSN3 in inflammatory and immune remodeling of the tumor microenvironment. Consistently, CSN3 expression was positively correlated with B-cell and CD8⁺ T-cell infiltration, indicating that CSN3-driven transcriptional programs may link tumor aggressiveness with immune microenvironment alterations.

overall_design: The study includes two groups: the experimental group (BGC823 gastric cancer cells with stable CSN3 knockdown via siRNA) and the control group (BGC823 cells transfected with empty vector). E Cells are cultured under standard conditions (37°C, 5% CO₂) to the logarithmic growth phase. CSN3 knockdown efficiency is validated using qRT-PCR and Western blot, ensuring a significant reduction in expression (>70%). Total RNA is extracted using TRIzol or commercial kits, followed by DNase treatment to eliminate genomic DNA contamination.

first: Dalai

last: Xu

first: Lei

last: Qiu

first: Feng

last: Lu

first: Yongchang

last: Miao


title: The Potential Core Role of the FN1-Hippo Signaling Axis in the Pathological Mechanism of Autism spectrum disorder

city: Jinan

first: Ziyun

address: No. 9-7 Jiangshuiquan Road, Lixia District,Jinan, Shandong

institute: Shandong Provincial Maternal and Child Health Care Hospital affiliated to Qingdao University

summary: Autism Spectrum Disorder (ASD) lacks reliable biomarkers and targeted therapies. This study integrated serum transcriptomics and proteomics from 13 ASD and 13 typically developing (TD) children to elucidate core molecular mechanisms. Differential expression analysis identified 6,563 genes (94.2% upregulated) and 157 proteins (75.2% downregulated), revealing widespread post-transcriptional dysregulation in ASD. Functional enrichment demonstrated abnormalities in energy metabolism, ciliary function, and chemical perception pathways. O2PLS multi-omics integration nominated FN1 as a pivotal cross-omics target, exhibiting transcriptional elevation but proteomic reduction, indicating post-transcriptional perturbation. The Hippo signaling pathway emerged as a key regulatory hub connecting omics layers, with its core components (YAP1, MST1) significantly downregulated. Validation in a valproic acid-induced SH-SY5Y neuronal model confirmed that Hippo pathway inhibition drove FN1 transcriptional upregulation and selectively induced interleukin-6 (IL-6) expression, establishing a novel Hippo-FN1-IL-6 axis. This axis mechanistically links developmental signaling defects and neuroinflammation in ASD pathogenesis. Collectively, we define post-transcriptional dysregulation as a molecular hallmark of ASD and identify the Hippo-FN1-IL-6 cascade as a central pathogenic mechanism. FN1 represents a potential diagnostic biomarker and therapeutic target, providing novel insights for ASD intervention strategies.

overall_design: Serum transcriptomic analysis of 13 children with autism spectrum disorder (ASD) and 13 typically developing (TD) children


title: Reference-guided genome assembly of long non-coding RNA transcripts reveals target genes associated with Crohn’s disease

city: Chapel Hill

first: Terrence

last: Furey

state: North Carolina

address: 120 Mason Farm Rd

institute: University of North Carolina at Chapel Hill

overall_design:
RNA-seq of colon tissue from CD patients and non-IBD controls

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

middle: Z

last: Sheikh

first: Meaghan

last: Kennedy Ng


title: DNA Methylation Profiles in Soybean Pol IV and V Mutants

first: Brandon

last: Le

overall_design: Two transgenic (T) and non-transgenic (NT) siblings for GmNRPD1, GmNRP(D/E)2, and GmNRPE1, respectively, were obtained for this study.

first: Xuemei

last: Chen