title: A human iPSC model of Tauopathies engineered for 4R Tau isoform expression endogenously develops late-stage neuronal Tau pathology

city: Munich

first: Dominik

last: Paquet

state: Bavaria

address: Feodor-Lynen-Str. 17

department: Institute for Stroke and Dementia Research

institute: University Hospital LMU Munich

summary: Tauopathies, such as Alzheimer’s disease and Frontotemporal Dementia, are common neurodegenerative diseases characterized by misfolding, hyperphosphorylation, and aggregation of Tau. Molecular mechanisms underlying Tauopathies are still poorly understood, which is in part due to a lack of human models autonomously developing major disease hallmarks. Formation of late-stage disease phenotypes may require adult Tau isoform expression, which contributes to Tau pathogenesis but is challenging to replicate in human stem-cell-derived systems, thus impeding research on underlying mechanisms and drug development. Here we show that induction of adult human brain-like 4R Tau isoform expression enables cell-intrinsic formation of late-stage Tauopathy hallmarks in iPSC-derived neurons engineered to contain synergistic Tau mutations, without exogenous sources of Tau pathology. Neurons accumulated seeding-competent, hyper-phosphorylated, fibrillar Tau in tangle-like structures. Furthermore, exclusive expression of mutant 4R in the absence of the 3R Tau isoform disproportionately intensified pathology, resulting in highly abundant Tau misfolding and aggregation. Finally, we provide proof-of-principle that our model can be translationally applied both to test chemical disease modulators and evaluate human Tau PET tracers. Collectively, our model corroborates the central role of 4R Tau isoform expression for pathogenesis in human neurons and enables novel investigations to elucidate mechanisms underlying human Tauopathy formation. Moreover, it may also serve as a platform supporting urgently needed development of disease-modifying drugs.

overall_design: Bulk RNA sequencing was performed on human induced pluriptent stem cell derived cells during dual-SMAD-inhibition directed cortical neuron differentiation to investigate changes occuring as a result of gene editing. Samples include wild type and 4 different lines with edits of the endogenous MAPT locus, as well as wild-type cells treated with Nocodazole as a control. Three biological replicates (i.e. independent differentiations) were analyzed for each sample at  day in vitro (DIV) 15 and 35.

first: Angelika

last: Dannert

first: Caterina

last: Carraro


title: ACBP: a poor-prognosis biomarker in sepsis and a target for disease mitigation [Lung]

status: Public on Jan 26 2026

city: PARIS

first: Guido

last: Kroemer

address: 15 rue de L'école de médecine

country: France

institute: Centre de Recherche des Cordeliers

type: Expression profiling by high throughput sequencing

summary: Sepsis remains a major clinical challenge, with high mortality and long-term disability despite current interventions. Here, we identify the tissue hormone acyl-CoA–binding protein (ACBP), also known as diazepam-binding inhibitor (DBI), as a biomarker and driver of poor outcome in sepsis. ACBP/DBI was elevated in the plasma of septic patients and associated with organ dysfunction and increased mortality. In murine models of endotoxemia, Escherichia coli infection, and polymicrobial sepsis, genetic deletion or antibody-mediated neutralization of ACBP/DBI conferred robust protection by enhancing pathogen clearance, dampening cytokine storm, and preserving organ function. Notably, ACBP/DBI inhibition could be favorably combined with glucocorticoids, enhancing survival and reversing histopathological, transcriptional, or metabolic signatures of septic shock across heart, kidney, liver, lung, spleen, and plasma. These findings position ACBP/DBI as a mechanistic amplifier of sepsis pathophysiology and propose its neutralization, alone or in combination with corticosteroids, as a promising therapeutic strategy to interrupt the fatal trajectory of septic shock.

overall_design: Eight-week-old male C57Bl/6J mice were randomly assigned to treatment groups and administered either a monoclonal antibody against ACBP/DBI (aDBI; 4h and 1h prior to surgery) or its isotype control (IgG), administered 1h before surgery. Sepsis was induced by cecal ligation and puncture (CLP) under isoflurane anesthesia. Briefly, the cecum was exteriorized, ligated at 75% of its length using non-absorbable 4-0 silk suture, and punctured once through-and-through with a 21-gauge needle. A small amount of fecal content was gently extruded, and the cecum was returned to the abdominal cavity. Sham-operated mice underwent the same procedure, including treatment injections, but without ligation or puncture. Mice that died within the first 24h post-surgery were considered to have succumbed to perioperative complications and were excluded from further analysis. For molecular analyses, organs were collected on the day of euthanasia (6h and 24h post-CLP) and immediately snap-frozen in liquid nitrogen. For RNA-sequencing library preparation, RNA was extracted from mouse lungs using RNA Plus Mini Kit (Qiagen) according to manufacturer’s instructions. The concentration and integrity of total RNA was analysed using electrophoretic separation on microfabricated chips in Agilent 2100 Bioanalyzer System (Agilent, CA, USA). After, mRNA-sequencing library preparation (1.5 µg total RNA per sample) was carried out on NovaSeq 6000 PE150 instrument (2 x 150 bp, 40 million reads per sample). For RNA-sequencing data analysis, Fastq files were align on mm10, Mus musculus genome, by Hisat2, BAM files were count by HTSeq-count. The obtained raw count files were analyse with R package (R Foundation for Statistical Computing; https://www.R-project.org/) DESeq2. Our genes of interest were selected based on the thresholds abs (Fold Change) ≥ 1.5 and a pvalue ≤ 0.05. Heatmaps were performed with the R package ComplexHeatmap, Venn diagrams with ggVennDiagram, all other plots are realized with ggplot2. Gene ontology was realized with gprofilr, clusterProfiler and enrichplot.

first: Flavia

last: Lambertucci

first: Omar

last: Motiño

first: Uxía

last: Nogueira-Recalde

first: Yan

last: Rong

first: Léa

last: Montégut

first: María

last: Pérez-Lanzón

first: Vincent

last: Carbonnier

first: Sijing

last: Li

first: Sylvère

last: Durand

first: Fanny

last: Aprahamian

first: Hui

last: Chen

first: Yanbing

last: Dong

first: Allan

last: Sauvat

first: Silvia

last: Mingoia

first: Sylvie

last: Lachkar

first: Ester Gloria

last: Saavedra Díaz

first: Jonathan

last: Pol

first: Federico

last: Pietrocola

first: Estela

last: Rocha-Oliveira

first: Roberto

last: Roncon-Albuquerque Jr

first: Francisco

last: Vasques-Nóvoa

last: Lozano-Rodríguez

first: José

last: Avendaño-Ortiz

first: Eduardo

last: López-Collazo

first: Mahmoud

last: Abdellatif

first: Isabelle

last: Martins


title: Targeting Fused in Sarcoma (FUS): A Novel Antisense Strategy for Treating Idiopathic Pulmonary Fibrosis [RNA-Seq PCLS]

city: bad nauheim

first: Stefan

last: Günther

address: ludwigtr. 43

country: Germany

institute: MPI for heart and lung research

summary: Fused in Sarcoma (FUS) is a highly conserved RNA-binding protein with essential roles in RNA processing and genomic stability. While extensively studied in the context of neurodegeneration, its involvement in fibrotic diseases—particularly idiopathic pulmonary fibrosis (IPF)—remains largely unexplored. This study investigates the pathological role of FUS in IPF and assesses its viability as a therapeutic target. Specifically, we examine how FUS dysregulation contributes to fibrotic signaling and evaluate whether therapeutic silencing of FUS offers a rational strategy to modulate disease progression. Functional assays were performed on primary lung fibroblasts derived from healthy donors and IPF patients to assess the effects of FUS overexpression and knockdown. Precision-cut lung slices (PCLS) and 3D-alveolosphere cultures from IPF patients were treated with a FUS-targeted antisense oligonucleotide (ASO;ION363). FUS-RNA interactions were mapped using CLIP-Seq, and global transcriptional changes following FUS inhibition were analyzed via RNA sequencing. FUS overexpression in healthy fibroblasts promoted proliferation, while its knockdown attenuated the hyperproliferative phenotype in IPF fibroblasts. IPF cells demonstrated aberrant cytoplasmic mislocalization of FUS. Standard-of-care treatments (pirfenidone, nintedanib) reduced FUS expression in PCLS. CLIP-Seq revealed FUS binding to a distinct set of pro-fibrotic RNAs in IPF. ION363 treatment downregulated fibrotic gene programs, including those linked to ECM remodeling, TGF-β signaling, and epithelial dysfunction. On the contrary, ION363 promoted functional markers and improved morphology in patient derived 3D-alveolospheres. We conclude that FUS is a pivotal regulator of fibrotic signaling in IPF and targeting FUS via ASO represents a promising therapeutic avenue for IPF.

overall_design: RNA-Seq profiling of precision cut lung slices (PCLS) from explanted lungs of IPF patients

first: Poornima

last: Mahavadi

last: Guenther


title: Targeting Fused in Sarcoma (FUS): A Novel Antisense Strategy for Treating Idiopathic Pulmonary Fibrosis [RNA-Seq IPF]

overall_design: RNA-Seq profiling of IPF fibroblasts treated or transfected as follows: Scr-ASO, ION363 (FUS-ASO), non-targeting siRNA (Scr), siRNA for FUS.


title: Smyd5 mediates IL-4 epigenetic control of macrophage antigen presentation to drive cooperative T cell-mediated tumor suppression [scRNA-seq]

city: Xiamen

first: dang

last: buyun

state: Fujian

address: Xiang 'an District Xiang Annan Road

country: China

institute: xiamen university

summary: IL-4 is classically associated with “M2” macrophages considered tumor-immunosuppressive, yet marker-based labels poorly reflect macrophage function in tumors. Reports of a non-canonical, IL-4–imprinted macrophage state (M2inf) with trained-immunity features prompted us to test whether such imprinting contributes to antitumor immunity in vivo. Here we show that, in B16F10 melanoma, IL-4 programs macrophages through the lysine methyltransferase Smyd5 to deposit promoter-proximal H3K36me3, increase MHC class II, and potentiate T cell activation. Myeloid Il4ra deletion increased tumor burden and reduced MHC class II and intratumoral T cell activation, whereas co-transfer of IL-4–primed macrophages suppressed tumors and expanded activated CD4 and CD8 T cells. Antitumor benefit required adaptive lymphocytes and macrophage-intrinsic MHC class II, as Rag1 deficiency or macrophage Rfx5 deletion abrogated tumor suppression. These findings identify a non-canonical, IL-4–imprinted macrophage program that enables antigen presentation and cooperative T cell immunity in this tumor context.

overall_design: Subcutaneous B16F10  tumor tissues were taken from the control group and the IL4 treatment group, CD45-positive immune cells were isolated by FACS, then 10x Genomic scRNA-seq library construction was performed

first: Buyun

last: Dang

first: Yuling

last: Hong

first: Qingxiang

last: Gao

first: Shih-Chin

last: Cheng


title: A hierarchical Rorc(γt) cis-regulatory cascade orchestrates differentiation of RORγt⁺ innate immune cells [ATAC-seq]

city: Fukuoka

first: Shinichiro

last: Sawa

address: 3-1-1 Maidashi, Higashiku

country: Japan

institute: Kyushu University

type: Genome binding/occupancy profiling by high throughput sequencing

summary: Beyond its well-established role in type 3 immunity, RORγt+ innate immune cells are also essential for secondary lymphoid organ (SLO) formation and gut homeostasis. However, the transcriptional regulatory mechanisms governing RORγt expression in these cells, including ILC3s, LTi cells, and antigen-presenting cells (APCs), remain largely unknown. Here, we identify two key cis-regulatory elements within conserved non-coding sequences (CNS) 9 and 11 in the Rorc locus, which are sequentially utilized during their differentiation. Initially, Runx-binding sites in CNS11 establish chromatin accessibility as early as the HSC stage. Notably, disruption of this chromatin priming prevents subsequent transcriptional activation, thereby abolishing the initial induction of RORγt in these cells. At later stages, CNS9 plays a critical role, particularly in the development of RORγt⁺ APCs, contributing to colonic pTreg induction. This hierarchical transcriptional regulation is essential for SLO formation, postnatal type 3 immunity, and restraining excessive intestinal type 2 immune responses through pTreg induction.

overall_design: ATAC-seq of HSC,MPP,aLP-ILCP,ILC2 and DP thymocyte collected from bone marrow, E14.5 fetal liver, small intestine and thymus of either Control, CNS11mut/mut, CNS114th/4th or VavCre Cbfb flox/flox mice.

first: Takuma

last: Fukui

first: Miyuki

last: Watanabe

first: Satoshi

last: Kojo

first: Eriko

last: Sumiya


title: ACBP: a poor-prognosis biomarker in sepsis and a target for disease mitigation II

first: Guido

last: Kroemer

summary: Septic shock remains a major clinical challenge, with high mortality and long-term disability despite current interventions. Here, we identify the tissue hormone acyl-CoA–binding protein (ACBP), also known as diazepam-binding inhibitor (DBI), as a biomarker and driver of poor outcomes in sepsis. ACBP/DBI was elevated in the plasma of septic patients, correlating with organ dysfunction and mortality. In murine models of endotoxemia, Escherichia coli infection, and polymicrobial sepsis, genetic deletion or antibody-mediated neutralization of ACBP/DBI conferred robust protection by enhancing pathogen clearance, dampening cytokine storms, and preserving organ function. Notably, ACBP/DBI inhibition could be favorably combined with glucocorticoids, enhancing survival and reversing transcriptional and metabolic signatures of septic shock across spleen, liver, heart, and kidney. These findings position ACBP/DBI as a mechanistic amplifier of sepsis pathophysiology and propose its neutralization—alone or combined with corticosteroids—as a promising therapeutic strategy to interrupt the fatal trajectory of septic shock.

overall_design: Eight-week-old male C57Bl/6J mice were randomly assigned to treatment groups and administered either a monoclonal antibody against ACBP/DBI (aDBI; 4h and1 h prior to surgery) or its isotype control (IgG), in combination with dexamethasone (DEX) or PBS 1X, administered 1h before CLP. Sepsis was induced by cecal ligation and puncture (CLP) under isoflurane anesthesia. Briefly, the cecum was exteriorized, ligated at 75% of its length using non-absorbable 4-0 silk suture, and punctured once through-and-through with a 21-gauge needle. A small amount of fecal content was gently extruded, and the cecum was returned to the abdominal cavity. Sham-operated mice underwent the same procedure, including treatment injections, but without ligation or puncture. Mice that died within the first 24h post-surgery were considered to have succumbed to perioperative complications and were excluded from further analysis. For molecular analyses, organs were collected on the day of euthanasia (24h post-CLP) and immediately snap-frozen in liquid nitrogen. For RNA-sequencing library preparation, RNA was extracted from mouse spleens using RNA Plus Mini Kit (Qiagen) according to manufacturer’s instructions. The concentration and integrity of total RNA was analysed using electrophoretic separation on microfabricated chips in Agilent 2100 Bioanalyzer System (Agilent, CA, USA). After, mRNA-sequencing library preparation (1.5 µg total RNA per sample) was carried out on NovaSeq 6000 PE150 instrument (2 x 150 bp, 40 million reads per sample). For RNA-sequencing data analysis, Fastq files were align on mm10, Mus musculus genome, by Hisat2, BAM files were count by HTSeq-count. The obtained raw count files were analyse with R package (R Foundation for Statistical Computing; https://www.R-project.org/) DESeq2. Our genes of interest were selected based on the thresholds abs (Fold Change) ≥ 1.5 and a pvalue ≤ 0.05. Heatmaps were performed with the R package ComplexHeatmap, Venn diagrams with ggVennDiagram, all other plots are realized with ggplot2. Gene ontology was realized with gprofilr, clusterProfiler and enrichplot.

first: Flavia

last: Lambertucci

first: Omar

last: Motiño

first: Uxía

last: Nogueira-Recalde

first: Yan

last: Rong

first: Léa

last: Montégut

first: María

last: Pérez-Lanzón

first: Vincent

last: Carbonnier

first: Sylvère

last: Durand

first: Fanny

last: Aprahamian

first: Hui

last: Chen

first: Yanbing

last: Dong

first: Allan

last: Sauvat

first: Silvia

last: Mingoia

first: Sijing

last: Li

first: Sylvie

last: Lachkar

first: Ester Gloria

last: Saavedra Díaz

first: Jonathan

last: Pol

first: Federico

last: Pietrocola

first: Estela

last: Rocha-Oliveira

first: Roberto

last: Roncon-Albuquerque Jr

first: Francisco

last: Vasques-Nóvoa

last: Lozano-Rodríguez

last: Avendaño-Ortiz


title: Activation of FXR regulates oxidative stress responses in human keratinocytes.

city: Nanjing

first: Zhiqiang

last: Huang

state: Jiangsu

address: Hankou 22

department: Medical School

institute: Nanjing University

summary: Psoriasis is a chronic and inflammatory skin disease that is characterized by red plaques covered with silvery-white scales. The pathogenesis of psoriasis involves a complex interplay between keratinocytes and immune cells, featuring of psoriasis include hyperproliferation and aberrant differentiation of keratinocytes in the epidermis, infiltration of immune cells, and angiogenesis in the dermis.

overall_design: In this study, we use human epidermal keratinocytes (HaCaT cells) as an in vitro model to examine the relationship between Farnesoid X Receptor (FXR) signaling and cellular lipid metabolism, focusing on bile acid (BA) homeostasis. We hypothesize that the BA-FXR regulatory axis plays a pivotal role in keratinocyte lipid handling and inflammatory responses, contributing to the pathophysiology of psoriatic skin lesions. Through integrated analyses of BA species, FXR activation status, and downstream lipid-metabolic pathways, we aim to elucidate the mechanistic basis by which BA-FXR signaling influences lipid synthesis, storage, catabolism, and BA-mediated inflammatory signaling in HaCaT cells. This study employs quantitative BA profiling, FXR perturbation (agonism/antagonism), lipidomics, and transcriptomic/proteomic readouts to map the regulatory network. By comparing in vitro findings with observations from psoriatic skin samples, we will assess the translational relevance of the BA–FXR axis as a therapeutic target for psoriasis and related inflammatory dermatoses.

first: Panpan

last: Lian

first: Hongwei

last: Wang


title: Cell-specific transcriptomics and silencing reveal aquaporin function in grass stomatal movements

city: Belvaux

first: Sylvain

last: Legay

address: 41, rue du Brill

department: ERIN department

country: Luxembourg

institute: Luxembourg Institute of Science and Technology

summary: The high efficiency of grass stomata is believed to be due to their structure and anatomy, with two dumbbell-shaped guard cells surrounded by two subsidiary cells (SCs) and an efficient functional molecular interaction between these cells. Important channels expressed in these cells are aquaporins (AQPs), which contribute to the dynamic of stomatal movement. To further investigate genes expressed in maize GCs and SCs, RNA sequencing was performed on microdissected GCs and SCs during day and night. A general transcriptomic analysis first revealed that genes upregulated in SCs compared to GCs during the day were primarily involved in lipid transport, lipid localization, and lipid metabolism, whereas genes more highly expressed in GCs were associated with photosynthesis, chloroplasts, and plastids. Interestingly, the expression of several AQP genes varied both spatially and temporally. For example, the plasma membrane aquaporin ZmPIP1;5 and ZmPIP2;5 displayed a higher expression in GCs than in SCs during the day, whereas ZmPIP1;3 and ZmPIP2;1 exhibited an opposite pattern. To examine the specific roles of AQPs in these cells, a CRISPR-based tissue-specific knockout system was successfully used to silence ZmPIPs belonging to the PIP1 subfamily in either maize GCs or SCs. The targeted knockout of ZmPIP1s in these cells impaired stomatal movements in response to light, ABA, and CO₂ compared with wild-type plants. Overall, these findings reveal transcriptomic specificities between maize GCs and SCs, providing valuable insights into the regulation of rapid stomatal movements in grasses, and highlight the role of ZmPIP1s in these processes.

overall_design: Maize B104 seeds were germinated and transferred to potting soil, as previously described. The plants were grown in a phytotron under a 16/8 h light/dark cycle (25/22 °C) and a daytime light intensity of 200 mmol. m−2. s−1 at the top of the leaves. Humidity was maintained between 60% and 70% in the growth chamber. Epidermal strips were peeled from the third leaf of two-week-old maize seedlings. They were placed on microscope glass slides (plain microscope slides 76x26mm, 0.8 mm x 1.00 mm, AGL4242) and flash-frozen with liquid nitrogen. The samples were immediately stored at -80 °C until microdissection. The samples were collected at two times, i.e., day (two hours after the light onset) and night (two hours after the light offset). Four independent collections were carried out. On the day before the microdissection, the peeled epidermal strips were freeze-dried at -40 °C for 10 h under pressure of 10 Pa in a Labconco® Free-Zone Plus freeze-drier. At the end of the process, the temperature slightly increased to room temperature for 3 h. A few drops of absolute ethanol were placed on the strips to flatten them. The samples were stored in a desiccator under vacuum at room temperature until microdissection, to avoid rehydration. Guard cells (GC) and subsidiary cells (SC) were collected using a PALM MicroBeam system (Carl Zeiss MicroImaging GmbH). GCs or SCs were selected using Zeiss software and cut using a laser. After cutting, cells were pressure catapulted and collected immediately in a tube with an adhesive cap (Carl Zeiss™ 415190-9211-000). Approximately 1500 cells were collected in one tube, and two tubes were used to collect cells for each sample.

first: Lei

last: Ding

first: Maxime

middle: J

last: Laurent

first: Stijn

last: Aesaert

first: Julien

last: Georgery

first: David

last: Cohen

first: Laurens

last: Pauwels

first: Didier

last: Le Thiec

first: Dirk

last: Inzé

first: François

last: Chaumont


title: Targeting Fused in Sarcoma (FUS): A Novel Antisense Strategy for Treating Idiopathic Pulmonary Fibrosis [CLIP-Seq]

first: Stefan

last: Günther

overall_design: CLIP-Seq of FUS from healthy donor (HD) and IPF fibroblasts and respective inputs (RNA from total cells)

first: Poornima

last: Mahavadi

last: Guenther


title: Genetic profiles of small intestinal and colonic metaplastic Paneth cells by spatial transcriptomics

city: Kyoto

first: Akira

last: Watanabe

state: Kyoto

address: Rm504, Miyako Bldg, 233, Isa-cho, kamigyo-ku

institute: CyberomiX Inc

summary: Metaplasia is an epithelial alteration that appears in chronic inflammatory diseases. In ulcerative colitis, Paneth cell metaplasia (PCM) is a well-recognized feature, but its role in the inflamed epithelium remains unclear. Using spatial transcriptomics, we characterized the gene expression profile of PCM, elucidated its regulatory mechanisms, and clarified its functional role in the inflamed colonic epithelium.

overall_design: Paired terminal ileum and colon biopsies were obtained from two ulcerative colitis patients during endoscopy. Spatial transcriptomics was performed on FFPE sections of these biopsy samples using the Visium HD platform (10x Genomics).

first: Tomohiro

last: Muto

first: Go

last: Ito


title: Plasma extracellular vesicle miRNA profiling in cervical cancer patients and healthy controls

city: Xining

first: Rui

last: yang

state: Qinghai

address: Affiliated Hospital of Qinghai University

type: Non-coding RNA profiling by high throughput sequencing

summary: Cervical cancer (CC) is a malignancy characterized by persistent HPV infection and tumor microenvironment remodeling. To explore the molecular characteristics of plasma extracellular vesicles (EVs) in CC, we performed miRNA sequencing on plasma EVs from 3 CC patients and 3 healthy controls. Differentially expressed miRNAs were identified, revealing potential biomarkers and providing insights into early diagnosis and therapeutic intervention.

overall_design:
Plasma EVs were isolated by ultracentrifugation from 3 CC patients and 3 healthy controls. miRNA libraries were prepared from the EV RNA and sequenced using Illumina HiSeq/NovaSeq. Differential expression analysis was performed to identify miRNAs associated with cervical cancer.

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

first: Tonghui

last: Bao


title: Association of Tumour-Associated Macrophage States with Non-conserved lncRNAs in Lung Cancer

city: Leuven

first: Eleonora

last: Leucci

address: Herestraat 49, bus 818 room 06.423

department: Oncology

country: Belgium

institute: KU Leuven

summary:
Tumour-associated macrophages (TAMs) are central players in the tumour microenvironment, driving cancer progression and modulating immune responses. Renowned for their ability to rapidly adapt to environmental changes, TAMs can adopt a wide range of functional phenotypes. However, the regulatory mechanisms underlying this functional plasticity are still not fully understood. Long non-coding RNAs (lncRNAs), as key regulators of epigenetic and post-transcriptional processes, are increasingly recognized for their potential role in TAM polarization.
In this study, we conducted a comprehensive comparative analysis of lncRNA expression in TAMs derived from both mouse and human lung carcinomas. Although we identified a small group of murine lncRNAs as potential human orthologs through orthogonal in silico approaches, the majority of murine lncRNAs lacked clear human equivalents.
Overall, our findings reveal distinct lncRNA expression patterns in lung carcinoma mouse and human TAMs, underscoring the importance of utilizing human-based models to thoroughly investigate the roles of lncRNAs in immune regulation and bridge the translational gap between murine and human cancer immunology.

overall_design: MHC-II low and high TAMs were extracted from Lewis lung carcinoma bearing mice.

first: Yvessa

last: Verheyden

first: Sonia

last: Cinque

first: Daliya

last: Kancheva

first: Jo

last: Van Ginderachter


title: African Pygmy Mouse iPSCs as a Model for In Vitro Embryogenesis, Interspecies Chimerism, and Blastocyst Complementation

city: Schwerzenbach

first: Adhideb

last: Ghosh

address: Schorenstrasse 16

department: Health Sciences and Technology

country: Switzerland

institute: ETH Zurich

summary: Somatic cell reprogramming into induced pluripotent stem cells (iPSCs) was achieved in various mammals, however assessing iPSC contribution to full-term chimeras beyond laboratory rodents remains challenging. Here, we demonstrate induction of pluripotency in male and female fibroblasts from the African Pygmy Mouse (APM), one of the smallest mammals. Using transcription factors and small molecules, we derived expandable APM-iPSCs that express pluripotency markers, differentiate into various cell types in vitro, and form gastruloids. Injection of APM-iPSCs into house mouse blastocysts generated full-term interspecies chimeras demonstrating extensive contribution to various tissues, including testicular germ cells. Notably, high APM contribution in organs such as heart and testes correlated with reduced organ size compared with mouse organs. Lastly, injection of APM-iPSCs into mouse blastocysts carrying a Pax7 ablation system enabled substantial production of APM muscle stem cells in chimeras. Collectively, this study establishes APM-iPSCs as a developmental model for pluripotency, differentiation and interspecies chimerism.

overall_design: Mouse-APM interspecies chimeras were produced through blastocyst injection into the Pax7-Cre/ERT2; Rosa26-loxP-STOP-loxP-Diphtheria toxin A (DTA) (B6.Cg-Pax7tm1(cre/ERT2)Gaka/J; B6.129P2-Gt(ROSA)26Sortm1(DTA)Lky/J) host, followed by tamoxifen-induced ablation of Pax7 expressing host cells.

first: Pjeter

last: Gjonlleshaj

first: Ajda

last: Lenardič

first: Monika

last: Tarnowska-Sengül

first: David

last: Taborsky

first: Christine L

last: Trautmann

first: João A

last: de Sousa

first: Nicola

last: Bundschuh

first: Frédéric

last: Veyrunes

first: Ataman

last: Sendoel

first: Ori

last: Bar-Nur


title: AtNUDT11 mediated dpCoA-RNA-seq defines epitranscriptomicdpCoA capped RNA [dpCoA_seq]

city: Beijing

first: Han

last: Wang

address: No.5 Yiheyuan Road

institute: Peking University

summary: Despite the parallel early discovery of dpCoA and NAD caps, dpCoA-RNA remains poorly characterized, largely due to the lack of selective decapping enzymes and reliable detection strategies. Evidence for its existence was limited to early bacterial studies，there is an urgent need for new and reliable technologies to quantify, identify, and investigate the molecular functions of the dpCoA cap.To map dpCoA-RNAs transcriptome-wide, we established dpCoA-RNA-seq, a sequencing method based on dpCoA decapping enzyme specificity, which revealed dpCoA-RNA features in Arabidopsis.

overall_design: RNA-seq profiling of Col-0 Arabidopsis seedlings treated ± AtNUDT11 at 12 days after germination for dpCoA-RNA identification.


title: Mitochondrial metabolism and signaling direct dendritic cell function in antitumor immunity [ATAC-seq2]

city: Memphis

first: Hongbo

last: Chi

state: TN

address: 262 Danny Thomas Place

department: Immunology

country: USA

institute: St Jude Children's Research Hospital

summary: ATAC-seq profiling of intratumoral cDC1s

overall_design: Intratumoral cDC1s were sorted from B16-OVA tumor-bearing mice at day 7 or day 21 after tumor inoculation, followed by ATAC-seq analysis

first: Hao

last: Shi

first: Zhiyuan

last: You


title: Mitochondrial metabolism and signaling direct dendritic cell function in antitumor immunity [microarray3]

summary: Transcriptional dissection of intratumoral cDC1s

overall_design: Intratumoral cDC1s were sorted from B16-OVA tumor-bearing mice at day 7 or day 21 after tumor inoculation, followed by microarray analysis


title: ACBP: a poor-prognosis biomarker in sepsis and a target for disease mitigation

first: Guido

last: Kroemer

overall_design: Eight-week-old male C57Bl/6J mice were randomly assigned to treatment groups and administered either a monoclonal antibody against ACBP/DBI (aDBI; 4h and 1h prior to surgery) or its isotype control (IgG), administered 1h before surgery. Sepsis was induced by cecal ligation and puncture (CLP) under isoflurane anesthesia. Briefly, the cecum was exteriorized, ligated at 75% of its length using non-absorbable 4-0 silk suture, and punctured once through-and-through with a 21-gauge needle. A small amount of fecal content was gently extruded, and the cecum was returned to the abdominal cavity. Sham-operated mice underwent the same procedure, including treatment injections, but without ligation or puncture. Mice that died within the first 24h post-surgery were considered to have succumbed to perioperative complications and were excluded from further analysis. For molecular analyses, organs were collected on the day of euthanasia (24h post-CLP) and immediately snap-frozen in liquid nitrogen. For RNA-sequencing library preparation, RNA was extracted from mouse livers using RNA Plus Mini Kit (Qiagen) according to manufacturer’s instructions. The concentration and integrity of total RNA was analysed using electrophoretic separation on microfabricated chips in Agilent 2100 Bioanalyzer System (Agilent, CA, USA). After, mRNA-sequencing library preparation (1.5 µg total RNA per sample) was carried out on NovaSeq 6000 PE150 instrument (2 x 150 bp, 40 million reads per sample). For RNA-sequencing data analysis, Fastq files were align on mm10, Mus musculus genome, by Hisat2, BAM files were count by HTSeq-count. The obtained raw count files were analyse with R package (R Foundation for Statistical Computing; https://www.R-project.org/) DESeq2. Our genes of interest were selected based on the thresholds abs (Fold Change) ≥ 1.5 and a pvalue ≤ 0.05. Heatmaps were performed with the R package ComplexHeatmap, Venn diagrams with ggVennDiagram, all other plots are realized with ggplot2. Gene ontology was realized with gprofilr, clusterProfiler and enrichplot.

first: Flavia

last: Lambertucci

first: Omar

last: Motiño

first: Uxía

last: Nogueira-Recalde

first: Yan

last: Rong

first: Léa

last: Montégut

first: María

last: Pérez-Lanzón

first: Vincent

last: Carbonnier

first: Sylvère

last: Durand

first: Fanny

last: Aprahamian

first: Hui

last: Chen

first: Yanbing

last: Dong

first: Allan

last: Sauvat

first: Silvia

last: Mingoia

first: Sijing

last: Li

first: Sylvie

last: Lachkar

first: Ester Gloria

last: Saavedra Díaz

first: Jonathan

last: Pol

first: Federico

last: Pietrocola

first: Estela

last: Rocha-Oliveira

first: Roberto

last: Roncon-Albuquerque Jr

first: Francisco

last: Vasques-Nóvoa

last: Lozano-Rodríguez

first: José

last: Avendaño-Ortiz

first: Eduardo

last: López-Collazo

first: Mahmoud

last: Abdellatif

first: Isabelle

last: Martins


title: Multi-omic profiling unveils molecular landscapes and heterogeneous tumor microenvironment in sinonasal squamous cell carcinoma [RPMI 2650 bulk ATAC-seq]

city: Cheongju

first: Chaelin

last: You

address: Chungdae-ro 1, Seowon-Gu

country: South Korea

institute: Chungbuk National University

summary: Sinonasal squamous cell carcinoma (SNSCC) is a rare and aggressive malignancy with limited treatment options. Here, we conduct a comprehensive multi-omic analysis, integrating bulk and single-cell transcriptomics, epigenomics, and DNA methylation profiling. Our study identifies distinct gene signatures, cellular compositions, and regulatory mechanisms that drive SNSCC pathogenesis. Epigenetic alterations reveal a regulatory landscape underlying transcriptional changes, and we characterize heterogeneous tumor cell populations with unique molecular profiles. Hypoxia-related cells emerge as key drivers of angiogenesis and disease progression. Notably, we uncover a critical interaction between hypoxic tumor cells and endothelial tip cells, mediated by factors such as adrenomedullin (ADM), highlighting a pivotal mechanism in tumor development. These findings provide valuable insights into the tumor microenvironment (TME) of SNSCC and suggest potential therapeutic targets to improve treatment strategies for this challenging malignancy.

overall_design: Bulk ATAC-seq was performed on RPMI 2650 cells exposed for 24 hours to either normoxia or hypoxia (1% O2).

first: Junho

last: Noh

first: Jiheui

last: Kim

first: Kyuho

last: Kang


title: AtNUDT11 mediated dpCoA-RNA-seq defines epitranscriptomicdpCoA capped RNA [RNA-Seq]

first: Han

last: Wang

overall_design: RNA-seq profiling of Col-0 Arabidopsis seedlings at 12 days after germination.


title: Trans-acting long non-coding RNA modulates long-range chromatin interactions associated with oncogenic MYC signaling [SMARCA1_ATAC-Seq]

city: Chicago

first: Rendong

last: Yang

state: IL

address: 420 E Superior St

department: Urology

institute: Northwestern University

summary: To investigate the functional role of the novel lncRNA IGF1R-AS1 in prostate cancer, we generated VCaP cells with siRNA-mediated knockdown and performed ATAC-seq to profile the corresponding changes in chromatin accessibility

overall_design: Analysis of ATAC-seq data for controls and its SMARCA1 KD derivatives in VCaP cell lines.

first: Tingyou

first: Yongyong

first: Qingshu

last: Meng

first: Yanan

last: Ren


title: Vascular invasion-associated gene expression is detectable in pre-surgical biopsies of stage I lung adenocarcinoma [bulkRNAseq_biopsies]

city: Boston

first: Adam

middle: C

last: Gower

state: MA

address: 72 East Concord Street, E632

department: Department of Medicine

institute: Boston University School of Medicine

summary: Microscopic vascular invasion (VI) predicts recurrence and benefit from lobectomy in stage I lung adenocarcinoma (LUAD) but cannot be accurately predicted before surgery. Thus, biomarkers that identify this aggressive tumor subset are needed. Here, we show that VI in stage I LUAD is associated with reproducible gene expression programs detectable beyond the invasive focus. Using bulk RNA sequencing of 162 resected tumors and spatial transcriptomics in a subset, we identify and characterize a VI-associated gene signature. A predictor derived from this signature is associated with VI and recurrence in an independent validation cohort and is robust to intra-tumor heterogeneity in multiregional sampling data. In a cohort of pre-surgical biopsies, predictor scores correlate with matched resections and show promising discrimination of VI. These findings indicate that VI-associated transcriptional changes extend across the tumor and are detectable in limited biopsy material, supporting further validation for preoperative risk stratification in stage I LUAD.

overall_design: Exome-capture RNA-seq was performed on an independent validation cohort consisting of 24 pre-surgical biopsies and 12 matched resected tumors from 24 patients with 8th edition TNM stage I LUAD. All samples were from patients not treated with neoadjuvant or adjuvant therapy. Cases were from Inova Schar Cancer Institute. FFPE pre-surgical biopsy samples were derived from needle biopsy, forceps biopsy, or fine needle aspiration. The determination of novel grade was based upon a representative FFPE block of the resected tumor.  The submitter declares that the raw data will be made available in dbGaP (https://www.ncbi.nlm.nih.gov/gap) due to patient privacy concerns.

first: Dylan

last: Steiner

first: Marc

middle: E

last: Lenburg


title: MYC modulates TOP2A diffusion to promote substrate detection and activity [CAD-seq]

city: Solna

first: Vladislav

last: Kuzin

state: Stockholm

address: Solnavägen 9

department: Cell and Molecular Biology

country: Sweden

institute: Karolinska Institute

summary: Topoisomerases are essential enzymes that alleviate DNA supercoiling by cleaving and resealing DNA strands. Regulation of their abundance and activity is crucial for maintaining genomic stability and supporting nuclear functions. Previously, we showed that the oncoprotein MYC recruits and stimulates topoisomerases to remove DNA entanglements generated by oncogenic transcription. Understanding this mechanism may suggest methods to inhibit MYC-driven topoisomerase activation, thereby selectively targeting tumor-specific transcription. Here, we demonstrate that the essential topoisomerase TOP2A in human cells exists in a dynamic equilibrium between sequestration in the nucleolus, substrate searching in transcription hubs, and active engagement on chromatin. This equilibrium is highly responsive to changes in DNA topology, allowing cells to regulate TOP2A levels in the nucleoplasm. Using single molecule tracking, we show that MYC accelerates TOP2A diffusion in cells. In vitro, we demonstrate that MYC decreases the size of TOP2A condensates, likely by limiting non-specific self interactions. By increasing TOP2A diffusion, MYC promotes substrate binding and increases TOP2A engagement on the chromatin genome-wide, revealing the mechanism underlying MYC stimulation of TOP2A activity.

overall_design: Covalent Adduct Detection of topoisomerase and sequencing (TOP CAD-seq) in HCT116 MYC-mAID cells for TOP2A in triplicates.

first: Donald

last: Cameron

first: Kathryn

last: Jackson

first: Evanthia

last: Iliopoulou

first: Laura

last: Baranello


title: Erythromycin-mediated complete co-flocculation between cyanobacterium and Penicillium: the easy-to-harvest co-cultivation without organic compound that increased CO2 fixation and biomass production.

city: Bangkok

first: Jidapa

last: Leksingto

country: Thailand

institute: Chulalongkorn

summary: Photoautotrophic cyanobacteria convert CO2 and produce various bioproducts. However, effective cell harvesting from liquid cultivation is a main obstacle. Automatic bio-flocculation provides a potential solution. In a Synechocystis sp. PCC 6803 (Syn) culture, we found that Syn co-flocculated with the natural contaminated fungi (identified as Penicillium sp.) as sphere biomass cluster with space inside, under the treatment of antibiotic erythromycin, but not without erythromycin. The optimized co-cultivation for five days using the initial Syn density of 0.4 OD730, 5 mg/100 ml fresh weight of Penicillium inoculum, and 5 µM EM in the BG11 medium with no organic compounds produced a complete biomass co-flocculation up to 2.0 g/L, equivalent to the atmospheric CO2 capture of 0.6 g/L/d: the 7.9-times biomass level and 7.2-times CO2 capture amount performed by the axenic Syn culture. A major constituent in Syn-Penicillium flocculated biomass is protein contents ranging from 39-61% of dry weight. In addition, increasing EM concentrations (from 0.3 to 10 µM) enlarged the co-flocculate diameter from x to Y and increasing the culture volumes (from 100 to 200-400 mL) altered co-flocculate surface texture from relatively smooth to rough with thorns. This co-flocculation may be further developed for CO2 capture and biomass utilization as amimal feed with a high protein contents. Syn with Penicillium_1; Synechocystis with Penicillium replicate 1 Syn with Penicillium_2; Synechocystis with Penicillium replicate 2 Syn with Penicillium_3; Synechocystis with Penicillium replicate 3 Syn without EM_1; Synechocystis without Erytromycin treatment replicate 1 Syn without EM_2; Synechocystis without Erytromycin treatment replicate 1 Syn without EM_3; Synechocystis without Erytromycin treatment replicate 1 Syn with EM_1; Synechocystis with Erytromycin treatment replicate 1 Syn with EM_2; Synechocystis with Erytromycin treatment replicate 1 Syn with EM_3; Synechocystis with Erytromycin treatment replicate 1 LR_Syn with Penicillium with EM_1; Large star structure of Synechocystis with Penicillium under EM treatment replicate 1 LR_Syn with Penicillium with EM_2; Large star structure of Synechocystis with Penicillium under EM treatment replicate 2 LR_Syn with Penicillium with EM_3; Large star structure of Synechocystis with Penicillium under EM treatment replicate 3 SS_Syn with Penicillium with EM_1; Small smooth structure of Synechocystis with Penicillium under EM treatment replicate 1 SS_Syn with Penicillium with EM_2; Small smooth structure of Synechocystis with Penicillium under EM treatment replicate 2 SS_Syn with Penicillium with EM_3; Small smooth structure of Synechocystis with Penicillium under EM treatment replicate 3

overall_design: Transcriptomic analysis was performed between the Synechocystis in the suspended Synechocystis cells with EM and the Synechocystis cells in the flocculated (with the Penicillium) Synechocystis-Penicillium flocculated biomass.  The results suggested that the presence of Penicillium did not significantly altered the expression levels of pillin genes. Thus the altered gene expression levels of pillin genes were results from the EM treatment. Samples include,Syn with Penicillium_1;

first: Tanakarn

last: Monshupanee

first: Panutchaya

last: Pichaiyotinkul


title: Single-cell transcriptional analysis of human pluripotent stem cell-derived heart epicardium-myocardium organoids uncover principals of human epicardial-derived cells specification and coronary vascular plexus development

city: Cantanhede

first: Jacek

middle: Dariusz

last: Marzec

address: Biocant Park

country: Portugal

institute: CoLAB AccelBio

summary: Normal heart function is supported by the integration of functional vasculature and the autonomic nervous system. Therefore, the development of in vitro human heart organoid models that recapitulate not only the myocardium but also the complementary cellular systems that sustain normal cardiac function is crucial for advancing clinical and biomedical applications. Here, we describe a physiologically relevant hiPSC-derived heart organoid model that recreates epicardium-myocardium interactions, exhibiting an in vivo-like structural organization and function. The model also enables compact myocardium development in close crosstalk with a coronary-like, self-organized vascular plexus, as well as epicardial-derived adipose tissue specification within the subepicardial space. We investigated the effect of PDGF-BB and VEGF-A signaling cues on heart organoid development, cellular composition, and spatial organization. Single-cell RNA sequencing revealed that PDGF-BB supplementation enhances subepicardial cell expansion and differentiation of epicardial-derived lineages, whereas VEGF-A promotes the robustness and functionality of the coronary-like vascular network. This system provides a valuable platform for addressing fundamental questions in cardiac development and disease, particularly those related to epicardial-derived cell specification and normal coronary vasculature formation and maturation.

overall_design: Single-cell RNA-seq profiling of hiPSC-derived heart organoid models generated with VEGFA and PDGFBB supplementation.

first: Mariana

middle: A

last: Branco


title: Trans-acting long non-coding RNA modulates long-range chromatin interactions associated with oncogenic MYC signaling [VCaP_HiChIP]

first: Rendong

summary: To investigate the functional role of the novel lncRNA IGF1R-AS1 in prostate cancer, we generated VCaP cells with siRNA-mediated knockdown and performed CTCF HiChIP to profile associated changes in 3D chromatin architecture.

overall_design: CTCF HiChIP-seq in VCaP cells with IGF1R-AS1 knockdown versus control.

first: Tingyou

last: Wang

first: Josh

last: Fry


title: Induction of a renal developmental cell state is associated with chemotherapy resistance in favorable-histology Wilms tumor [HiC]

first: Hongjian

last: Jin

department: Center for Applied Bioinformatics

summary: Children with favorable histology Wilms tumor (FHWT) who experience disease relapse or whose tumors exhibit blastemal predominance after chemotherapy often have poor outcomes. We established a FHWT patient-derived xenograft model, KT-47, that exhibited blastemal predominance after chemotherapy treatment with vincristine, actinomycin, and doxorubicin (VAD) and ultimately developed complete resistance to VAD after serial exposures to this combination. Histologic analyses and comprehensive multi-omics approaches were used to evaluate changes associated with resistance. CUT&TAG identified increased transcriptionally active H3K4me3 at stem cell and nephrogenesis gene promoters among the most different regions in KT-47 resistant compared to the KT-47 pretreatment model including the HOXB cluster, HOXC cluster, MYCN, SIX2, IGF2, CITED1, and OSR1. In contrast, decreased H3K27me3 was identified at HOX gene cluster and nephrogenesis gene promoter regions. The most significantly upregulated transcript and protein that associated with resistance in KT-47 was the let7 microRNA processor LIN28B. LIN28B upregulation was associated with copy number gain at MYCN and plasticity of cancer cells marked by open chromatin at the LIN28B locus rather than expansion of a minor subclone expressing LIN28B present in the original primary tumor material. The stem cell-associated multidrug resistance protein ABCB1 was upregulated in epithelial cells in association with an inter-chromosomal interaction between chromosomes 1 and 7. The impact of these findings at MYCN, LIN28B, and ABCB1 were validated in additional WT models and samples. Overall, these results support de-differentiation of FHWT cancer cells to a stem-like state which is associated with chemotherapy resistance. Targeting epigenetic modifiers that modulate differentiation of cancer cells with a stem-like phenotype could be a future treatment strategy in chemotherapy resistant FHWT.

overall_design: Chromosome-chromosome interactions were profiled using Hi-C of KT-47 pretreatment (KT-47PT) and KT-47 resistance (KT-47R1) samples. KT-47 pretreatment received no chemotherapy in the xenograft model. KT-47R1 exhibited complete resistance to vincristine, actinomycin-D, and doxorubicin.

first: Andrew

last: Murphy

first: Beisi

last: Xu

first: Carolyn

last: Jablonowski


title: Induction of a renal developmental cell state is associated with chemotherapy resistance in favorable-histology Wilms tumor [CUT&Tag]

overall_design: CUT&TAG analysis of KT-47 pretreatment (KT-47PT) and KT-47 resistance (KT-47R1) samples. KT-47 pretreatment received no chemotherapy in the xenograft model.  KT-47R1exhibited complete resistance to vincristine, actinomycin-D, and doxorubicin.

first: Surbhi

last: Sona


title: Induction of a renal developmental cell state is associated with chemotherapy resistance in favorable-histology Wilms tumor [RNA-seq]

overall_design: RNA-seq profiling of KT-47 pretreatment (KT-47PT), KT-47 pre-resistance, and KT-47 resistance (KT-47R1 and KT-47R2) samples. KT-47 pretreatment received no chemotherapy in the xenograft model. KT-47 pre-resistance received vincristine, actinomycin-D, and doxorubicin in the xenograft model but did not yet demonstrate resistance. KT-47R1 and KT-47R2 exhibited complete resistance to vincristine, actinomycin-D, and doxorubicin.


title: Optimizing Single-Cell Long-Read Sequencing for Enhanced Isoform Detection in Pancreatic Islets [sc_spleen]

city: Aurora

first: Maria

middle: Skjoett

last: Hansen

state: CO

address: 1775 Aurora Ct

department: Pediatrics

institute: University of Colorado Anschutz Medical Campus

summary: The goal of this study was to optimize single-cell long-read RNA sequencing in pancreatic islets to enable accurate isoform-level gene expression analysis. We aimed to overcome key technical limitations—including insufficient read lengths, high error rates, and transcript abundance bias—that have hindered long-read sequencing in single cells. Specifically, we compared 5’ and 3’ library preparation strategies and evaluated transcript depletion methods to improve detection of low-abundance isoforms. Our objective was to establish a robust protocol that enhances isoform identification and reveals differential transcript usage across pancreatic islet cell types.

overall_design: Single-cell RNA-seq libraries from dissociated pancreatic islets of 10-week-old C57BL/6 mice. We generated three libraries: one generated with 3’ 10x Genomics technology, one generated with 5’ 10x Genomics technology, and one generated with 5’ 10x Genomics technology with protocol modifications (extention time and dNTP concentration). The 3' library was sequenced on a Illumina short-read sequencer. The two 5' libraries were sequenced on an Oxford Nanopore long-read sequencer.

middle: S

first: Christopher

last: Hill

first: Lori

last: Sussel

first: Kristen

middle: L

last: Wells


title: Induction of a renal developmental cell state is associated with chemotherapy resistance in favorable-histology Wilms tumor [methylation]

type: Methylation profiling by genome tiling array

overall_design: Illumina methylation beachip array profiling of KT-47 pretreatment (KT-47PT), KT-47 pre-resistance, and KT-47 resistance (KT-47R1 and KT-47R2) samples. KT-47 pretreatment received no chemotherapy in the xenograft model. KT-47 pre-resistance received vincristine, actinomycin-D, and doxorubicin in the xenograft model but did not yet demonstrate resistance. KT-47R1 and KT-47R2 exhibited complete resistance to vincristine, actinomycin-D, and doxorubicin.


title: Effect of pharmacologic or genetic PIKFYVE inhibition in GEP-NET [RNA-Seq]

city: Ann Arbor

first: Arul

last: Chinnaiyan

state: MI

address: 1500 East Medical Center Dr

department: MCTP

institute: University of Michigan

summary: This study aims to elucidate the transcriptomic changes and metabolic reprogramming in gastroenteropancreatic neuroendocrine tumor (GEP-NET) cells following PIKfyve inhibition, using both genetic (CRISPR-mediated knockdown) and pharmacological (Apilimod treatment) approaches. The research focuses on the impact of PIKfyve inhibition on lipid metabolism, cholesterol homeostasis, and mTOR signaling in QGP-1, BON-1, and GOT-1 cell lines. By analyzing RNA sequencing data from these experimental conditions, we seek to identify differentially expressed genes and enriched pathways associated with PIKfyve inhibition. This investigation is part of a broader effort to develop novel combination therapies that could potentially overcome resistance to mTOR inhibitors, the current standard of care for advanced GEP-NETs. The study's findings may provide insights into the therapeutic potential of targeting PIKfyve-driven lipid metabolism in combination with mTOR inhibition, potentially offering new strategies to improve treatment efficacy and patient outcomes in GEP-NETs and other mTOR-driven cancers.

overall_design: RNA-seq profiling of QGP1 cells with or without PIKFYVE knockdown; or QGP1 cells transcriptome changes after Apilimod or Torin1 treatment.

first: Yizhi

last: Cao

first: Yuanyuan

last: Qiao

first: Caleb

last: Cheng

first: Xuhong

first: Andrej

last: Coleski

first: Eleanor

last: Young


title: Multi-omic profiling unveils molecular landscapes and heterogeneous tumor microenvironment in sinonasal squamous cell carcinoma [RPMI2650 bulk RNA-seq]

first: Chaelin

last: You

overall_design: Bulk RNA-seq was performed on RPMI 2650 cells exposed for 24 hours to either normoxia or hypoxia (1% O2).

first: Junho

last: Noh

first: Jiheui

last: Kim

first: Kyuho

last: Kang


title: Targeting Notch signaling to restore neural development and behavior in mouse models of ASD [RNAseq_embryo_hanno]

city: Wako

first: Yoko

last: Hanno

state: Saitama

address: 2-1 Hirosawa

institute: RIKEN Center for Brain Science

summary: Autism spectrum disorder (ASD) is a neurodevelopmental disorder with diverse genetic and environmental origins, yet whether these factors converge on common molecular pathways remains unclear. This study identifies dysregulation of the Notch signaling pathway as a shared mechanism in both hereditary and nonhereditary ASD models. Aberrant histone deacetylase 3-mediated epigenetic regulation of Notch signaling during embryonic forebrain development disrupts the specification of caudal ganglionic eminence (CGE) progenitors into vasoactive intestinal peptide (VIP+) GABAergic interneuron subtypes (VIP-INs). CGE-specific ablation of Notch1/2 genes in ASD models restores the loss of VIP-INs, normalizes maladaptive excitatory and inhibitory balance, and selectively improves social behaviors. Remarkably, a single antenatal dose of a γ-secretase inhibitor ameliorates multiple ASD-associated neuronal, behavioral, and transcriptomic changes in adult models. The study indicates a strong convergence of ASD-related factors on Notch signaling dysregulation and establishes this pathway as a promising therapeutic target for developmental and behavioral deficits in ASD.

overall_design: RNA-seq profiling of embryonic whole brain from wildtype mice and valproic acid or poly(I:C) exposed mice.


title: Beyond BRCA deficiency: Clinical and molecular predictors of survival in patients with BRCA-deficient tubo-ovarian high-grade serous carcinoma [RNA-Seq]

city: Melbourne

first: Dale

last: Garsed

state: Victoria

address: 305 Grattan St

department: Cancer Research

country: Australia

institute: Peter MacCallum Cancer Centre

summary: Homologous recombination DNA repair deficient (HRD) tumors account for about 50% of tubo-ovarian high-grade serous carcinomas (HGSC) and are associated with a high response to platinum-based chemotherapy. However, a subset of patients with HRD tumors have unexpected resistance to chemotherapy and experience short survival. Our study compared BRCA-deficient and proficient HGSC among patients with short (<3 years, the lowest quartile of overall survival (OS)) versus longer-term (>3 year OS) to identify prognostic markers and potential therapeutic opportunities.  Primary tumors from a cohort of patients with advanced-stage HGSC (n=154) enriched for those with HRD tumors and short survival (n=42) were analyzed using whole-genome sequencing, bulk RNA-sequencing, and DNA methylation profiling. A subset of HRD tumors (n=143) were characterized for immune cell densities by multiplex immunofluorescence. Clinicopathological features were assessed in 1,389 patients with HGSC, including 282 with pathogenic germline BRCA variants (gBRCApv). Findings were validated in two international HGSC cohorts: the Ovarian Tumor Tissue Analysis consortium (n=5,875) and Multisciplinary Ovarian Cancer Outcome Group (n=895). In gBRCApv-carriers, residual disease following surgical cytoreduction was not associated with shorter OS unlike in non-carriers where it was strongly associated. While most patients with gBRCApv had a more favorable OS compared to non-carriers, a survival advantage was not apparent in those with variants located outside of BRCA1 exon 10/23 and BRCA2 exon 11/27. Patient survival correlated with HRD score, such that those with a score ≥63 had significantly longer OS compared to those with HRD scores of 42-63 and <42. While higher HRD scores were associated with better survival outcomes, most gBRCApv carriers with a short survival had tumor HRD scores that exceeded the threshold typically considered predictive of a good response to carboplatin or PARP inhibitors. BRCA2-deficient HGSC with loss of the tumor suppressor NF1 was associated with exceptionally favorable outcome (median OS 17 years), whereas amplification of both PIK3CA and RAD21, was associated with poor outcome in BRCA2-deficient HGSC (median OS 2.9 years). The density of tumor-infiltrating CD8+ PD-1+ T cells was prognostic for OS in gBRCApv-carriers. In summary, rather than simply the presence or absence of a germline BRCA pathological variant influencing patient survival, the co-occurrence of specific somatic gene alterations, the extent of immune cell infiltration, the level of homologous recombination deficiency, and BRCA-variant location may modify clinical outcomes in patients with BRCA-deficient HGSC. Analysis of exceptional outcome patients, in this case gBRCApv-carriers with an atypically short survival, may identify determinants of outcome applicable to the wider HGSC patient population.

overall_design:
Transcriptomic profiling was done on 23 high grade serous ovarian cancer samples, all of which were primary tumors. 77 primary tumor samples from GSE209964 and 53 primary tumor samples from GSE211669 were also used as part of the cohort.

***************************************************************
Raw data uploaded to European Genome-phenome Archive (EGA) repository under the accession code EGAD00001015499
***************************************************************

first: Tibor

last: Zwimpfer

first: Ahwan

last: Pandey

first: David

last: Bowtell


title: Mitochondrial metabolism and signaling direct dendritic cell function in antitumor immunity [microarray2]

first: Hongbo

last: Chi

summary: Transcriptional dissection of splenic WT and OPA1-deficient cDC1s

overall_design: Splenic cDC1s were sorted from WT or CD11c-Cre; OPA1 flox mice, followed by microarray analysis

first: Hao

last: Shi

first: Zhiyuan


title: Effect of pharmacologic or genetic PIKFYVE inhibition in GEP-NET [CRISPR]

first: Arul

last: Chinnaiyan

overall_design: Genes were screened for essentiality in GEP-NET cancer cells after 14-days of growth using the human kinome CRISPR knockout pooled libraries (Brunello), Addgene #1000000083. Days 0 and 14 were screened using each half-pool  separately, yielding 4 total screens. The half-pools containing sgRNA sets 1-4 and sets 5-8 are here labeled "A" and "B", respectively.

first: Yizhi

first: Yuanyuan

first: Brian

last: Magnuson


title: Mitochondrial metabolism and signaling direct dendritic cell function in antitumor immunity [microarray1]

summary: Transcriptional dissection of cDC1s with polarized mitochondria or cDC1s with depolarized mitochondria

overall_design: Splenic [TMRM/MG]hi or [TMRM/MG]lo cDC1s were sorted from WT mice, followed by microarray analysis


title: Targeting Notch signaling to restore neural development and behavior in mouse models of ASD [RNAseq_htr]

overall_design: RNA-seq profiling of adult forebrain from wildtype and Notch conditional knockout mice, with or without prenatal valproic acid exposure.


title: Optimizing Single-Cell Long-Read Sequencing for Enhanced Isoform Detection in Pancreatic Islets [sc_islet]

first: Maria

last: Hansen

first: Christopher

last: Hill

first: Lori

last: Sussel

first: Kristen

last: Wells


title: Induced Uterine Infection Perturbs Bovine Endometrial Function

city: Gainesville

first: John

middle: James

last: Bromfield

state: FL

address: 2250 Shealy Drive, Dept of Animal Sciences, Rm 108

department: Animal Sciences

institute: University of Florida

summary: Uterine diseases in dairy cattle are associated with reduced fertility, but the specific mechanisms of disease mediated subfertility are not fully elucidated. We hypothesized that an intrauterine infusion of Escherichia coli and Trueperella pyogenes would alter the endometrial transcriptome at a time coincident with conceptus elongation, and compromise oocyte developmental competence. Sixty-one non-lactating Holstein cows received an intrauterine infusion of either saline (n = 29) or pathogenic E. coli and T. pyogenes (n = 32) to induce acute endometrial inflammation. Endometrial samples were collected via cytobrush 41 d after infusion and analyzed by RNA sequencing. Bacteria infusion altered the expression of 203 genes in the endometrium 41 d after infusion. Top upregulated genes were GSTA3, PVALB, JAKMIP2, FOLH1B, TCF23, and top downregulated genes were MYMK, LOC104974498, CDRT1, KIAA0408, SLC45A2. The differentially expressed genes were functionally annotated to 54 canonical pathways with glutathione-mediated detoxification being the top predicted pathway altered following bacteria infusion. Collectively, this work demonstrates that bacterial infections can have lasting effects on the uterus which may provide a link to the long-term subfertility of cows after uterine disease.

overall_design: RNA-seq profiling of endometrial cytobrush samples collected on day 16 of the esrous cycle, 41 days after intrauterne infusion of E. coli MS499 and T. pyogenes MS249 or PBS control.

first: Zackary

middle: K

last: Seekford


title: VAMP7-dependent late endosomal secretion of ER and mitochondrial proteins impacts the tumor microenvironment and macrophage engagement

city: Paris

first: Thierry

last: Galli

address: 102 Rue de la Sante

institute: Institute of Psychiatry and Neuroscience of Paris

summary: Late endosomal secretion is an unconventional secretion mechanism that depends on the SNARE protein VAMP7. We previously showed that VAMP7 mediates the secretion of the ER protein Reticulon3.  However, the functional relevance and molecular mechanism of this secretory pathway remain unclear. Here, we show that VAMP7 knockout cells  exhibit impaired secretion of ER- and mitochondrial-derived proteins and signs of ER and mitochondrial stress. In addition, pharmacological induction of organellar stress enhances the VAMP7-dependent secretion. We assess the pathophysiological significance of this mechanism using a preclinical glioblastoma model. VAMP7 knockout glioblastoma cells implanted in male rat brain develop into larger, more necrotic tumors with reduced macrophage infiltration compared to controls, suggesting that VAMP7-dependent late endosomal secretion contributes to the tumor microenvironment and affects macrophage infiltration. Together, our results support a model in which late endosomal secretion functions as an organelle quality-control and stress-communication mechanism, with particular relevance to cancer.

overall_design: Quadriplicate samples of WT, VAMP7KO and ATG5KO NRK cells grown in basal condition in Growth Medium


title: Multi-omic profiling unveils molecular landscapes and heterogeneous tumor microenvironment in sinonasal squamous cell carcinoma [Bulk RNA-seq]

first: Chaelin

last: You

overall_design: Bulk RNA-seq data were collected from seven tumor and seven normal nasal tissues of patients with sinonasal squamous cell carcinoma.

first: Jihwan

last: Park

first: Keunsoo

last: Kang

first: Jaewoo

first: Jungyeon

last: Jang

first: Myeongsang

last: Yu

first: Yoosam

last: Chung

first: Jiheui

last: Kim

first: Kyuho


city: Shanghai

first: Jiachen

last: Wang

state: Shanghai

address: No. 2005, Songhu Road

department: Institute of Plant Biology

institute: Fudan University

summary: To investigate the distribution patterns of histone modifications across the genome in osldl3 mutants, we analyzed the data derived from ChIP-seq.

overall_design: ChIP-seq of histone modifications in rice NiP and osldl3 using H3, H3K4me1, H3K4me2, H3K4me3 antibodies.

first: Jiabing

last: Wu

first: Kangxi

last: Du

first: Wenhao

last: Xie

first: Xiang

last: Li

first: Xiaolong

first: Aiwu

last: Dong


title: Single cell variant to enhancer to gene map for coronary artery disease [HI-ChIP]

city: Singapore

first: Roger

last: Foo

address: 14 Medical Drive, MD6

country: Singapore

institute: National University of Singapore

summary: Although genome wide association studies (GWAS) in large populations have identified hundreds of variants associated with common diseases such as coronary artery disease (CAD), most variants lie within non-coding regions of the genome, rendering it difficult to determine the downstream causal gene and cell type. Here, we performed paired single nucleus gene expression and chromatin accessibility profiling from 44 human coronary arteries. To link disease variants to molecular traits, we developed a meta-map of 88 samples and discovered 11,182 single-cell chromatin accessibility quantitative trait loci (caQTLs). Heritability enrichment analysis and disease variant mapping demonstrated that smooth muscle cells (SMCs) harbor the greatest genetic risk for CAD. To capture the continuum of SMC cell states in disease we used single cell caQTL modeling for the first time in tissue to uncover QTLs which are cell state aware and expand our insight into gene regulation in heterogenous cell populations. We identified a variant in the COL4A1/COL4A2 CAD GWAS locus which becomes a caQTL as SMCs de-differentiate through a transcription factor binding site change for EGR1/2. To unbiasedly prioritize functional candidate genes, we built a genome-wide single cell variant to enhancer to gene (scV2E2G) map in human CAD to link disease variants to causal genes in cell types. Using this approach, we found several hundred genes predicted to be linked to disease variants in different cell types. We validated these predictions using enhancer targeted perturb sequencing (TAP-seq). Next, we performed genome-wide HiC in 16 human coronary arteries to build tissue specific gene regulatory networks and map disease variants to integrated chromatin hubs and distal target genes not previously implicated. Using this approach, we show that rs4887091 within the ADAMTS7 GWAS locus modulates function of a super chromatin interactome through a change in a CTCF binding site. Finally, by integrating human genetics with single cell multi-omics we show that CAD genetic risk is enriched in de-differentiated fibromyocytes. Collectively we provide a disease agnostic framework to translate human genetic findings to identify pathologic cell states and genes driving disease, producing a comprehensive scV2E2G map with genetic and tissue level conviction for future mechanistic and therapeutic studies.

overall_design:
At least one million human healthy coronary artery smooth muscle cells (HCASMC) (Thermo Scientific, Product code C-017-5C, Lot. 1689414) and human healthy coronary artery endothelial cells (HCAEC) (ATCC, Product code PCS-100-020, Lot 62382179) were crosslinked with 1% Formaldehyde.
The initial Hi-C portion followed the Arima HiC protocol described in the Arima High Coverage Hi-C Kit (Arima Genomics, Material Part Number: A410110). For the immunoprecipitation step, sheared chromatin after the Hi-C portion of the protocol was immunoprecipitated with 5 μg of H3K27ac antibody (Abcam, ab4729) with 50 μl of protein G Dynabeads (Invitrogen 10004D) and allowed to incubate overnight at 4ºC. The protein G Dynabeads were washed and the immunoprecipitated DNA was de-crosslinked at 67ºC for 2 hours and eluted (50 mM sodium bicarbonate, 1% SDS).
Subsequently, Dynabeads MyOne Streptavidin C1 beads (Invitrogen 65002) were used to enrich ligated junctions as per Hi-C protocol. Library preparation was performed using the NEB Ultra II library preparation kit (NEB, E7645L), according to the manufacturer’s protocol. 12 PCR cycles were performed using indexed primers and subsequently DNA fragments between 300 to 500 bp were size selected using the Omega MagBind NGS cleanup Magnetic beads (Omega M1378).

first: Chang Jie Mick

last: Lee

first: Anene-Nzelu

last: Chukwuemeka

first: Amrute

last: Junedh

first: Stitziel

last: Nathan


title: Vascular invasion-associated gene expression is detectable in pre-surgical biopsies of stage I lung adenocarcinoma [Spatial Transcriptomics]

first: Adam

last: Gower

overall_design: 16 samples from 14 patient tumors within the validation cohort were selected for 10x Genomics Visium for FFPE spatial whole-transcriptome profiling. All samples were selected to be stage IA/IB at the time of collection except for one that was upstaged to stage IIA under the 8th TNM edition (this sample was excluded from the bulk RNA-seq validation cohort when evaluating the performance of VI predictor scores). Samples were chosen based on 1) the presence of pathological features of interest (e.g., VI foci, representative LUAD histologic patterns) and 2) more than 50% of RNA fragments being greater than 200 nucleotides (DV200) after extraction with the AllPrep DNA/RNA Universal Kit (Qiagen) during bulk RNA-seq library preparation.

first: Dylan

last: Steiner

first: Marc

last: Lenburg


title: Nucleoli-localized KANSL2 as an epigenetic regulator of ribosome biogenesis in glioblastoma cells.

city: Capital federal

first: Carolina

last: Perez-Castro

state: Argentina

address: Godoy Cruz 2090

department: Cell plasticity

country: Argentina

institute: IBioBA (Instituto de investigacion en Biomedicina de Buenos Aires - Instituto partner de la sociedad Max Planck)

summary: KANSL2 is a subunit of the non-specific lethal (NSL) chromatin-modifying complex involved in epigenetic reprogramming and plays a critical role in tumorigenesis of glioblastoma (GBM), by enriching the GBM stem-like cell population. Analysis of KANSL2 expression in TCGA-GBM tumor samples and GTEx normal brain tissue confirmed that KANSL2 is highly expressed in GBM and positively correlates with both the stemness index score and ribosomal protein mRNA expression. KANSL2 localized to nucleoli, depending on the cell cycle phase, suggesting its dynamic shifting during the cell cycle. Ectopic overexpression of KANSL2-RFP upregulated 45S pre-rRNA and 28S rRNA expression, concomitant with higher cell proliferation. In contrast, KANSL2 downregulation decreased proliferation, 45S pre-RNA and 28S rRNA expression levels, and acetylated levels of H4 at lysine 5 and 8 in the rDNA promoter region, suggesting KANSL2 is necessary for proper rRNA gene expression potentially via histone acetylation. In support, RNA-seq analysis of patient-derived GBM spheroids silenced for KANSL2 showed significant downregulation of ribosomal biogenesis-related genes. Collectively, these findings revealed an unprecedented role of KANSL2 as a positive regulator of rRNA expression in GBM, suggesting it to be a critical mediator of cell stemness and proliferation, making it an attractive target for potential therapy.

overall_design: F18-1 and F2-4 cells used for the RNA-seq assay were obtained from the University of Colorado, Colorado, USA, through the Neurosurgery Nervous System Biorepository (protocol COMIRB #13–3007), with no expiration date. According to the WHO CNS5 (2021) classification, F18-1 is a grade 4 glioblastoma (GBM), IDH-wildtype, with O(6)-methylguanine-DNA methyltransferase (MGMT) promoter methylation. F2-4 is a grade 4 IDH-mutant astrocytoma (positive for the IDH1 mutation by immunohistochemistry), negative for epidermal growth factor receptor (EGFR) amplification, but positive for the loss of phosphatase and tensin homolog (PTEN) sequences relative to chromosome 10 centromere sequences. F18-1 was derived from a primary tumor, whereas F2-4 was obtained from a resection of a recurrent tumor.  Briefly, stable cells expressing small hairpin RNA of a non-targeting control and two KANSL2-targeting sequences were cultured in serum-free medium supplemented with B27, N2, 20 ng/ml bFGF, 20 ng/ml EGF, 2 mM L-glutamine, 2 mM non-essential amino acids, 50 U/ml penicillin/streptomycin, and 75 µg/ml low-endotoxin bovine serum albumin (Sigma, USA). Cells were plated onto Geltrex (A1413202)-coated plates for three days before being harvested for sequencing.

first: Nicolás

last: Budnik


title: Trans-acting long non-coding RNA modulates long-range chromatin interactions associated with oncogenic MYC signaling [RNA-seq]

first: Rendong

last: Yang

summary: To investigate the function and affected pathways of novel lncRNA IGF1R-AS1 in the prostate cancer, we established VCaP cell lines in which SMARCA1/SMARCA4 has been knocked down by siRNA.

overall_design: Comparative gene expression profiling analysis of RNA-seq data for controls and its SMARCA1/SMARCA4 KD derivatives in VCaP cell lines.

first: Tingyou

first: Yongyong

first: Yanan

last: Ren


title: Vascular invasion-associated gene expression is detectable in pre-surgical biopsies of stage I lung adenocarcinoma [bulkRNA-seq]

summary: Microscopic vascular invasion (VI) predicts recurrence and benefit from lobectomy in stage I lung adenocarcinoma (LUAD) but cannot be accurately predicted before surgery. Thus, biomarkers that identify this aggressive tumor subset are needed. Here, we show that VI in stage I LUAD is associated with reproducible gene expression programs detectable beyond the invasive focus. Using bulk RNA sequencing of 162 resected tumors and spatial transcriptomics in a subset, we identify and characterize a VI-associated gene signature. A predictor derived from this signature is associated with VI and recurrence in an independent validation cohort and is robust to intra-tumor heterogeneity in multiregional sampling data. In a cohort of pre-surgical biopsies, predictor scores correlate with matched resections and show promising discrimination of VI. These findings indicate that VI-associated transcriptional changes extend across the tumor and are detectable in limited biopsy material, supporting further validation for preoperative risk stratification in stage I LUAD.

overall_design:
Exome capture RNA-sequencing was performed on a discovery cohort (n=108 patient tumors) of 8th edition TNM stage 0/1 LUAD tumors not treated with neoadjuvant therapy. Cases were from Boston Medical Center (BMC) and Lahey Hospital & Medical Center (LHMC). RNA-sequencing was also performed on an independent validation cohort (n=61 tumors, n=60 patients) of 8th edition TNM stage I/II LUAD not treated with neoadjuvant therapy. All samples were selected to be stage IA/IB at time of collection except for one tumor that was upstaged to stage IIA under the 8th TNM edition. Cases were from LHMC. The submitter declares that the raw data will be made available in dbGaP (https://www.ncbi.nlm.nih.gov/gap) due to patient privacy concerns.

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Submitter states that missing raw data are being made available for controlled access in dbGaP.
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title: Vascular invasion-associated gene expression is detectable in pre-surgical biopsies of stage I lung adenocarcinoma

overall_design: Refer to individual Series


title: Optimizing Single-Cell Long-Read Sequencing for Enhanced Isoform Detection in Pancreatic Islets [bulk_islet]

first: Maria

last: Hansen

overall_design: Bulk RNA-seq libraries og C57BL/6 mouse pancreatic islets, with and without insulin depletion. Two replicates of each.

first: Christopher

last: Hill

first: Lori

last: Sussel

first: Kristen

last: Wells


title: ChIP-seq of H3K4me1, H3K4me2, H3K4me3, H3K36me1, H3K36me2, and H3K36me3 for Physcomitrella patens (Physcomitrium patens).

first: Jiachen

last: Wang

summary: We performed H3K4 and H3K36 methylation occupancy analysis (ChIP-seq) for Physcomitrella patens.

overall_design: H3K4 and H3K36 methylation levels on wild-type Physcomitrella patens genes.

first: Jiabing

last: Wu

first: Kangxi

last: Du

first: Wenhao

last: Xie

first: Xiang

last: Li

first: Xiaolong

first: Aiwu

last: Dong


title: Trans-acting long non-coding RNA modulates long-range chromatin interactions associated with oncogenic MYC signaling [ATAC-seq]

summary: To investigate the function and affected pathways of novel lncRNA IGF1R-AS1 in the prostate cancer, we established VCaP cell lines in which IGF1R-AS1 has been knocked down by siRNA.

overall_design: Analysis of ATAC-seq data for controls and its IGF1R-AS1 KD derivatives in VCaP cell lines.

first: Qingshu

last: Meng


title: Multi-omic profiling unveils molecular landscapes and heterogeneous tumor microenvironment in sinonasal squamous cell carcinoma [DNA methylation]

first: Chaelin

last: You

summary: Sinonasal squamous cell carcinoma (SNSCC) is a rare and aggressive malignancy with limited treatment options. Here, we conduct a comprehensive multi-omic analysis, integrating bulk and single-cell transcriptomics, epigenomics, and DNA methylation profiling. Our study identifies distinct gene signatures, cellular compositions, and regulatory mechanisms that drive SNSCC pathogenesis. Epigenetic alterations reveal a regulatory landscape underlying transcriptional changes, and we characterize heterogeneous tumor cell populations with unique molecular profiles. Hypoxia-related cells emerge as key drivers of angiogenesis and disease progression. Notably, we uncover a critical interaction between hypoxic tumor cells and endothelial tip cells, mediated by factors such as adrenomedullin (ADM), highlighting a pivotal mechanism in tumor development. These findings provide valuable insights into the tumor microenvironment (TME) of SNSCC and suggest potential therapeutic targets to improve treatment strategies for this challenging malignancy.

overall_design: DNA methylation profiles of three tumor and three normal nasal tissues from patients with sinonasal squamous cell carcinoma were generated using the Illumina HumanMethylation EPIC array platform.

first: Jihwan

last: Park

first: Keunsoo

last: Kang

first: Jaewoo

first: Jungyeon

last: Jang

first: Myeongsang

last: Yu

first: Yoosam

last: Chung

first: Jiheui

last: Kim

first: Kyuho


title: Transcriptome data (mRNA-seq) for Chlamydomonas reinhardtii wild type.

first: Jiachen

summary: Gene expression profiling analysis of RNA-seq data for Chlamydomonas reinhardtii.


title: Transcriptome data (mRNA-seq) for Physcomitrella patens (Physcomitrium patens) wild type.

summary: Gene expression profiling analysis of RNA-seq data for Physcomitrella patens (Physcomitrium patens).

first: Jiabing


title: ChIP-seq for Ehd3 and SDG724 using HA or GFP antibodies.

summary: To investigate the distribution patterns of Ehd3 and SDG724 across the rice genome, we analyzed the data derived from ChIP-seq.

first: Kangxi


title: Transcriptome data (mRNA-seq) for NiP, ehd3-1, sdg724-1, and ehd3 sdg724.

summary: To explore how Ehd3 and SDG724 regulate gene transcription at the genome-wide level, we conducted RNA-seq analyses of NiP, ehd3-1, sdg724-1, and ehd3 sdg724.

overall_design: Comparative gene expression profiling analysis of RNA-seq data for WT and mutants.

first: Wenhao


title: High throughput sequencing data for Oryza sativa, Chlamydomonas reinhardtii, and Physcomitrella patens

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

sample_organism:
Chlamydomonas reinhardtii
Physcomitrium patens
Oryza sativa

first: Xiang


title: Multi-omic profiling unveils molecular landscapes and heterogeneous tumor microenvironment in sinonasal squamous cell carcinoma [snMultiome-seq]

overall_design: Single-cell multiomics data were collected from two tumor tissues of patients with sinonasal squamous cell carcinoma and two normal nasal tissues of healthy donors.


title: Rational design of immune gene therapy combinations via in vivo CRISPR activation screening of tumor microenvironment modulators [scRNA-seq]

city: New Haven

first: Chuanpeng

state: CT

address: 850 West Campus Dr

department: Genetics

institute: Yale University School of Medicine

summary: The hostile tumor microenvironment (TME) is major challenge for cancer immunotherapies. Here, we design and perform TME-targeted in vivo CRISPR activation (CRISPRa) screens to uncover factors that promote anti-tumor immunity, culminating in rationally designed immune gene therapy combinations. Through adeno-associated virus (AAV) delivery, we find that multiplexed activation of pooled immunoregulatory genes encoding antigen presentation, cytokine, and co-stimulation molecules (APCM) leads to enhanced anti-tumor immunity. A CRISPRa screen targeting APCM genes in metastatic tumors identifies CD80, TNFSF14, CXCL10, TNFSF18, TNFSF9, and IFNG as the top immunostimulatory candidates. Further optimization pinpoints 4-1BBL(TNFSF9) + IFNG + IL12B (4II) as a potent streamlined therapeutic combination. AAV delivered 4II has potent in vivo anti-tumor efficacy in multiple tumor models, by enhancing tumor antigen presentation while simultaneously promoting the infiltration, activation, and expansion of anti-tumor T cells. We further demonstrate that APCM therapy synergizes with CAR-T therapy against human solid tumors in vivo. CRISPRa screens and gene activation systems targeting APCM factors thus represent a powerful approach for rapid development of off-the-shelf immune gene therapies against solid tumors.

overall_design: Seven days post CAR-T cell infusion, CD3+ T cells were isolated from the lung following treatment with either AAV-vector or 4II.

first: Feifei

last: Zhang

first: Ryan

middle: D

last: Chow

first: Emily

last: He

first: Lvyun

last: Zhu

first: Shan

last: Xin

first: Daniyal

last: Mirza

first: Yanzhi

last: Feng

first: Xinyu

last: Ling

first: Qin

last: Han

first: Sidi

last: Chen

first: Guangchuan


title: ChIP-seq of H3K4me1, H3K4me2, H3K4me3,H3K36me1, H3K36me2, and H3K36me3  for Chlamydomonas reinhardtii.

first: Jiachen

last: Wang

summary: We performed H3K4 and H3K36 methylation occupancy analysis (ChIP-seq) for Chlamydomonas reinhardtii.

overall_design: H3K4 and H3K36 methylation levels on wild-type Chlamydomonas reinhardtii genes.

last: Wu

last: Du

last: Xie

last: Li

first: Xiaolong

first: Aiwu

last: Dong


title: Targeting NPM1 Epigenetically Promotes Post-infarction Cardiac Repair by Reprogramming Reparative Macrophage Metabolism [RNA-Seq]

first: Zhenzhen

last: Zhan

address: Jimo Road 150

department: Research Center for Translational Medicine

institute: Shanghai East Hospital, Tongji University School of Medicine,

summary: Background: Post-infarction heart failure is attributed to ischemia-induced myocardial inflammation and unfavorable remodeling, with reparative macrophages playing a crucial role in limiting excessive fibrosis and promoting cardiac repair via cytokine secretion and cross-cell interactions. Hence, a timely and adequate transition of macrophage phenotypes is essential for proper wound healing post-MI, but the precise mechanisms underlying this process remain incompletely elucidated. Methods: To elucidate the function of NPM1 in post-infarct cardiac repair, we generated macrophage-specific NPM1 knockout mouse models. Additionally, Cut&Tag assays were conducted on cardiac macrophages for the first time to explore the epigenetic mechanisms underlying NPM1-mediated regulation of macrophage metabolic reprogramming. Results: Macrophage-specific deletion of NPM1 in MI mouse models resulted in reduced tissue fibrosis and enhanced cardiac repair by promoting the phenotypic transition of macrophages towards a reparative state. NPM1 deletion also led to a shift in macrophage metabolism from glycolysis to mitochondrial OXPHOS via inactivation of the mTOR cascades. Mechanistically, we demonstrated that IL-4 induced NPM1 oligomerization, which recruited histone demethylase KDM5b to the promoter region of Tsc1, ultimately leading to macrophage metabolic rewiring. Antisense oligonucleotides and inhibitory compounds targeting NPM1 exhibited notable protective effects on cardiac repair post-MI. Conclusions: Our study demonstrates that NPM1 may serve as a promising prognostic biomarker and a valuable therapeutic target for ischemia-induced heart failure, shedding new light on the understanding of post-infarct cardiac repair and may pave the way for the development of innovative therapeutic strategies.

overall_design: WT and Npm1-cKO mice were sacrificed at MI-D3 or MI-D5 by CO2 anesthesia. The hearts were rapidly extracted and used to isolate cardiac macrophages. The total RNA for one sample was extracted from 1×10^6 isolated cardiac macrophages, qualified, and used to make the sequence.

first: Sheng


title: Rational design of immune gene therapy combinations via in vivo CRISPR activation screening of tumor microenvironment modulators [CRISPR]

first: Chuanpeng

overall_design: To generate metastatic lung tumors and perform in vivo screening under immune pressure, E0771-APCM library cells were injected into 8-12 weeks old female C57BL/6J mice intravenously.

last: Zhang


title: Reduced DNAJB1 expression contributes to aging insubstantia nigra: insights from single-nuclei RNA seq

first: Zhixin

last: Bai

address: Dongan Road

department: Department of Human Anatomy & Histoembryology, School of Basic Medical Sciences

summary: In this study, we established a comprehensive single-nucleus transcriptomic atlas of human SN across lifespan, from adolescents to centenarians. Notably, we discovered that the protein folding pathway was commonly downregulated among different SN cell types across aging. With orthogonal expression and functional validations, we demonstrated that a decrease in Dnajb1 expression results in reduced potassium ion channels, resulting in elevated neuronal excitability, cellular senescence, reactive astrocytes, ultimately impaired motor balance, and behavioral outputs phenotyping anxiety and depression.

overall_design: To investigate the specific molecular changes in the substantia nigra of mice after DNAJB1 knockdown, we used three control groups and a knockdown group for RNA-seq analysis.


title: Rational design of immune gene therapy combinations via in vivo CRISPR activation screening of tumor microenvironment modulators [Bulk RNA-seq]

overall_design: E0771 cells were transduced with AAV-Vector, AAV-IFNG, IL12B, 41BBL and AAV-4II for 5 days.

first: Feifei

first: Ryan

last: Chow

last: He


summary: To investigate the distribution patterns of histone modifications across the genome in different mutants, we analyzed the data derived from ChIP-seq.

overall_design: ChIP-seq of histone modifications in rice NiP, ehd3-1, sdg724-1, and ehd3sdg724 using H3, H3K4me1, H3K4me2, H3K4me3, H3K36me1, H3K36me2, and H3K36me3 antibodies.

first: Jiabing

first: Kangxi

first: Wenhao

first: Xiang


title: miR-291a-3psuppresseslungcancerproliferation,invasion,andmigrationbytargeting relevantgenes.

status: Public on Jan 25 2026

city: Xining City

first: Guowei

last: Liu

state: Qinghai Province

address: No. 2, Gonghe Road, Chengdong District

department: Department of Thoracic Surgery

institute: Qinghai Provincial People's Hospital

summary: Lung cancer is the leading cause of cancer-related mortality worldwide, and overall patient prognosis remains poor. MicroRNAs function as either tumor suppressors or oncogenes and are critically involved in various stages of lung cancer development and progression. However, the functional role and underlying mechanisms of miR-291a-3p in lung cancer remain largely unknown.

overall_design: In this study, we systematically investigated the biological functions and molecular mechanisms of miR-291a-3p by overexpressing it in murine Lewis lung carcinoma cells, followed by integrated analyses combining RNA sequencing, bioinformatics, and clinical data validation.

first: Huanjuan

last: Yang

first: Gang

first: Shunjun

first: HuSai

last: Ma


title: Kidney Transcriptome Sequencing of Mice with Diabetic Nephropathy

city: Shenzhen

first: Shu

address: 1017 Dongmen North Road, Luohu District, Shenzhen

institute: shenzhen people's hospital

summary: Aging is a major risk factor for diabetic kidney disease (DKD), with both conditions exhibiting similar renal pathology. We identify the energy-sensing molecule Retinoic acid-related orphan receptor γ (RORγ) as significantly downregulated in diabetic and aged kidneys. Tubule-specific RORγ deficiency exacerbates kidney injury, whereas its overexpression protects. Mechanistically, RORγ stabilizes insulin-induced gene 1 (INSIG1) by upregulating the deubiquitinase YOD1 and enhancing AMPK activity via CAB39, which together promote INSIG1 phosphorylation and subsequent stabilization. Stabilized INSIG1 potently blocks the ER-to-Golgi transport and activation of SREBP2 (cholesterol synthesis) and STING (inflammatory signaling). In diabetes, RORγ itself is suppressed transcriptionally by CTCF and functionally by impaired AMPK/SIRT1 signaling, which hinders its activation. Importantly, administration of a RORγ agonist or RORγ-enriched exosomes effectively alleviates diabetic kidney injury. Thus, RORγ emerges as a key regulatory node that mitigates DKD and renal aging by co-regulating AMPK-mediated metabolic and STING-driven innate immune pathways through INSIG1 stabilization.

overall_design: db/db mice were used as the diabetic model and db/m mice as the control, followed by renal transcriptome sequencing.


title: Combination of the SOX6-induced cellular senescence and senolytic therapy improves the chemosensitivity of cervical cancer

city: Beijing

first: Han

last: Zheng

address: 38 Xueyuan Road, Haidian District

institute: Peking University Health Science Center

summary:
Sex-determining region of Y-related high-mobility-group box 6 (SOX6) is a member of SOX gene family and inhibits the proliferation of cervical cancer cells by inducing cell cycle arrest. However, the mechanisms, final cell fate and significance of these cell cycle arrested cervical cancer cells induced by SOX6 remains unclear.
To investigate downstream genes regulated by SOX6 gene in cervical cancer cells, microarray analysis was performed.

overall_design: HeLa cells were transfected with either SOX6 vector or control vector. Total RNA was extracted and performed microarray analysis. Affymetrix U133 plus 2.0 arrays were used.

first: Mingchen

last: Shi

first: Hongxin

last: Huang

first: Jie


title: Targeting NPM1 Epigenetically Promotes Post-infarction Cardiac Repair by Reprogramming Reparative Macrophage Metabolism

first: Zhenzhen

overall_design: Refer to individual Series


title: Trans-acting long non-coding RNA modulates long-range chromatin interactions associated with oncogenic MYC signaling [RNA-seq]

city: Chicago

first: Rendong

address: 420 E Superior St

institute: Northwestern University

overall_design: Comparative gene expression profiling analysis of RNA-seq data for controls and its IGF1R-AS1 KD derivatives in VCaP cell lines.

first: Tingyou

last: Wang

first: Yanan

last: Ren


title: Subfamily-level Comparative Transcriptomics of Key Immune Regulators in Plants and Suspension Cells Reveals Novel Rice Blast-resistance Genes

city: Kurashiki

first: Yoji

last: Kawano

state: Okayama

department: Institute of Plant Science and Resources

institute: Okayama University

summary: Plants activate pattern-triggered immunity (PTI) through key immune components, including pattern recognition receptors (PRRs), receptor-like cytoplasmic kinases (RLCKs), and transcription factors (TFs), to combat pathogens. However, a comprehensive transcriptional overview of these immune regulators at the subfamily level during biotic stress in rice is currently lacking. The aims of this study were to characterize the expression profiles of OsPRRs, OsRLCKs, and OsTFs and establish a robust pipeline for selecting novel candidate genes involved in plant immunity. We identified differentially expressed genes (DEGs) within these families using transcriptomic data from both rice plants infected with Magnaporthe oryzae infection and rice suspension cell treated with chitin treatment. Our analysis revealed the transcriptional regulation of well-known immune-related subfamilies of OsPRRs, OsRLCKs, and OsTFs, such as RLK-LRR-XII and RLCK-VII, and identified several novel subfamilies with high proportions of DEGs that may contribute to pathogen perception and plant defense. We demonstrated that selecting candidates from overlapping DEGs between plant and suspension cell systems is an effective strategy for screening genes involved in rice immunity. Using this pipeline, novel immune regulators were identified, and their functions were confirmed. Two RLCKs, i.e., OsRLCK298 and OsBSR1, act as positive regulators of immunity against rice blast fungus, whereas two transcription factors, i.e., OsERF65 and OsERF96.2, act as negative regulators. This study provides a valuable transcriptomic resource and establishes a validated pipeline for gene discovery that could be applied to other stress responses and in other plant species.

overall_design: RNA-seq profiling of wild rice plants and their knockout mutants when sprayed with Magnaporthe oryzae and harvested at 48 hpi


title: Targeting NPM1 Epigenetically Promotes Post-infarction Cardiac Repair by Reprogramming Reparative Macrophage Metabolism [CUT&Tag]

overall_design: WT and Npm1-cKO mice suffered from MI for 3 days, and WT mice that underwent a sham operation were sacrificed by CO2 anesthesia. The hearts were rapidly extracted and used to isolate cardiac macrophages. The bone marrow-derived cells were isolated from WT and Npm1-cKO mice and stimulated with 50 ng/ml M-CSF for 7 days to develop into macrophages.

first: Sheng


title: ATAC-seq Reveals that Heme Regulates the Transcriptional Activity of Transcription Factors Driving CD8⁺ T Cell Exhaustion

city: Tianjin

first: Yingxi

last: Xu

address: 288 Nanjing Road

department: State Key Laboratory of Experimental Hematology

institute: Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College

summary: Regulatory heme is known to influence cellular behavior by modulating the activity of hemoproteins. We hypothesized that elevated levels of regulatory heme might drive T cell exhaustion through the modulation of transcription factor activity. To test this hypothesis, we first confirmed that treatment with hemin, a heme analog, effectively increased intracellular regulatory heme levels in T cells. To assess the transcriptional and chromatin changes induced by hemin, we performed ATAC-seq on CD8⁺ T cells treated with or without exogenous hemin. The ATAC-seq analysis revealed that hemin-treated T cells displayed a distinct chromatin accessibility landscape compared to vehicle-treated controls. Integration of ATAC-seq and transcriptomic data using the Taiji analytical algorithm revealed that hemin modulates the activity of transcription factors involved in T cell exhaustion, including BACH2, MYB, MAF, BATF, RUNX3, and PRDM1.

overall_design: Primary normal CD8 T cell treated with 25uM Hemin or veicle for bulk ATAC-seq analysis, 4 replicates are included in each group.

first: Yu-Ming

last: Chuang

first: Ping-Chih

last: Ho


title: Global regulation of mediated by the histidine-responsive local transcription factor HutC in Pseudomonas aeruginosa

city: Auckland

first: Xue-Xian

address: 3a Symonds Street

country: New Zealand

institute: University of Auckland

summary: Pseudomonas aeruginosa is a metabolically versatile environmental pathogen whose virulence relies on coordinated expression of catabolic genes, particularly the histidine utilization (hut) operon. Disruption of the hut operon reduces virulence, but the underlying mechanism remains rudimentary. Here, we genetically characterized the histidine-responsive transcriptional factor HutC in P. aeruginosa PAO1, alongside HutC in the non-pathogenic strain P. fluorescens SBW25. Two important features emerged. First, HutC recognizes two distinct DNA-binding motifs with little sequence similarity; notably, a noncanonical binding site was identified in the hutF promoter of SBW25 but was absent in PAO1. Second, HutC exhibits low-affinity binding to genes beyond histidine catabolism and contributes to the expression of multiple virulence traits. These findings identify HutC as a local regulator linking histidine catabolism with virulence and as a unique prokaryotic model for studying how noncanonical transcriptional factor-DNA interactions achieve binding specificity, a phenomenon so far investigated only in eukaryotes.

overall_design: Compare trasncriptomes between wild-type PAO1 with each of three derived mutants with hutC expressed at different levels. Bacteria were gorwn on minimal medium supplemented with histidine (10 mM) as the sole source of carbon and nitrogen.

first: Xinyi


title: Progressive lung fibrosis and calumenin deficiency

city: Jinan

first: Huirui

state: -- None selected --

address: 44 Wenhuaxi Road

institute: Shandong University

summary: Progressive lung fibrosis is linked to aging-related dysfunction in fibroblasts, which remains poorly understood. We aimed to assess the impact of calumenin deficiency on fibroblast senescence and lung fibrosis.

overall_design: In the present work, we knocked out or knocked down calumenin in fibroblasts and conducted RNAseq analysis to investigate the effects of calumenin on senescence and fibrosis signaling pathways in fibroblasts. By integrating proteomics data results, we aimed to provide a more precise analysis.

first: Ting

last: Dong