title: Comprehensive interrogation of chemo-genomic interactions between DNA damaging agents and DNA damage repair genes with targeted CRISPR knockout screening

city: West Haven

first: Francesc

last: Lopez

state: CT

department: Department of Genetics

institute: Yale University

summary: Genetic instability is a hallmark of cancer, often arising from mutations to DNA damage repair and response (DDR) genes. Classical genetic, biochemical and structural approaches have elucidated the foundational mechanisms of DDR pathways and provided a scientific understanding of their involvement in repair of broad classes of DNA-damaging agents (DDAs). However, given the chemical diversity of DDAs and resultant DNA lesions, along with the multitude of interconnected DDR factors, the chemogenomic landscape of DDA–DDR interactions remains incompletely mapped. To this end, we developed a DDR-targeted, CRISPR knockout screening approach and assessed relationships among 353 DNA repair genes and 15 DDAs in LN229 glioma cells. Within this dataset of 5295 DDR-related chemogenomic interactions, we identified many established interactions and discovered novel ones. For example, we observed a specific role of TC-NER in the repair of adducts generated by monofunctional alkylating agents, a role for the FA pathway in addressing methyl lesions, overt differences in DSB repair following treatment with topoisomerase I and II poisons, and repair dependencies associated with imidazotetrazine derivatives temozolomide, mitozolomide, and KL-50. Future directions will continue to investigate the mechanisms of novel chemogenomic interactions that we have uncovered as well as work to identify chemogenomic interactions amenable to clinical translation.

overall_design: NOT PROVIDED; REQUESTED

first: Collin

last: Heer

first: James

middle: L

last: Elia

first: Spenser

last: Johnson

first: Vijay

last: Menon

first: Sofia

last: Arbelaez

first: Sam

last: Friedman

last: Lopez-Giraldez

first: Seth

last: Herzon

first: Ranjit

last: Bindra

first: Susan

middle: E

last: Gueble


title: Gene expression signatures for mouse organ aging

status: Public on Dec 15 2025

city: Kyoto

first: Masahiro

last: Kameda

state: Kyoto

address: Sakyoku Shougoin Kawaramati 54

department: Geriatric Unit

country: Japan

institute: Kyoto University Hospital

summary: We asseced gene expression profiles in 4 organs including lung, liver, kidney and white adipose tissue between 10 week (n=3) old and 90 week old mice (n=3).

overall_design: Each organs of C57BL/6J mice male mice were collected. Total RNA of each organ was extracted and microarray data analysis was performed.

first: Hiroshi

last: Kondoh

first: Takumi

last: Mikawa


title: Enterocloster citroniae and related gut microbiome species modulate Vibrio cholerae biofilm formation through the production of bioactive small molecules

status: Public on Dec 14 2025

city: Lawrence

first: Luis Caetano

last: Antunes

state: KS

address: 1200 Sunnyside Avenue

country: USA

institute: University of Kansas

type: Expression profiling by high throughput sequencing

summary: Cholera is a deadly diarrheal disease that affects millions of people globally. Although V. cholerae, the causative agent of the disease, has been extensively studied in isolation, it was relatively recently that scientists started investigating its interactions with the gut microbiota. Our group and others previously showed that microbiota-derived metabolites significantly influence V. cholerae behavior. By investigating how an organic extract of human feces affects V. cholerae gene expression, we recently showed that gut metabolites strongly suppress swimming motility, a virulence factor important for host colonization. Interestingly, extracts of pure cultures of a single gut commensal, Enterocloster citroniae, recapitulated this inhibitory effect. Here, we present a comprehensive examination of the effect of small molecules produced by E. citroniae and related species on V. cholerae behavior. We show that E. citroniae small molecules inhibit motility by various V. cholerae strains. We also show that several phylogenetically related species produce this activity, although the magnitude of the effect varies between strains. Using biofilm formation assays in static and shear flow conditions, we show that V. cholerae strongly induces biofilm formation in response to E. citroniae metabolites. Transcriptome and reporter analyses show that several genes involved in the synthesis of an extracellular polysaccharide are induced by growth in the presence of E. citroniae metabolites. Lastly, we show that V. cholerae interactions with host epithelial cells are also modulated by compounds produced by this commensal. These findings advance our understanding of microbiome-pathogen interactions and how commensal bacteria influence V. cholerae virulence through the production of small molecules. In the future, this knowledge may be used to design novel microbiome-based therapeutic approaches to combat cholera and other infections.

overall_design: RNA-seq profiles of Vibrio cholerae C6706 grown in the absence or presence of an organic extract of Enterocloster citroniae WAL17108 cultures.

first: Antunes

last: Caetano


title: A role for the cholinergic neuron circadian clock in RNA metabolism and mediating neurodegeneration [Bmal1-KO]

city: Chicago

first: Sharon

last: Tam

state: IL

address: 303 E Chicago Ave, Rm 13-270

institute: Northwestern University

summary: Circadian clocks are encoded by a transcription-translation feedback loop that aligns physiological processes with the solar cycle. Previous work linking the circadian clock to the regulation of RNA-binding proteins (RBPs) provides a foundation for the vital examination of their mechanistic connections in the context of amyotrophic lateral sclerosis (ALS)—a fatal neurodegenerative disease commonly marked by disrupted RBP function. Here, we reveal that the spinal cord cholinergic neuron rhythmic transcriptome is enriched for genes associated with ALS and other neurodegenerative diseases. We show that there is time-of-day-dependent expression of ALS-linked RBP transcripts and rhythmic alternative splicing of genes involved in microtubule cytoskeleton organization, intracellular trafficking, and synaptic function. Through in silico analysis of RNA sequencing data from sporadic ALS patients, we find that gene expression profiles altered in disease correspond with rhythmic gene networks. Finally, we report that clock disruption through cholinergic neuron-specific deletion of clock activator BMAL1 increases neurodegeneration and drives time-of-day-dependent alternative splicing of RNA processing genes. Our results establish a role for the cholinergic neuron circadian clock in RNA metabolism and mediating neurodegeneration.

overall_design: RNA-seq profiling of Bmal1 knockout mouse spinal cord cholinergic neurons and controls collected at ZT8 and ZT20

middle: B

first: Nathan

middle: J

last: Waldeck

first: Matthew

last: Wright

first: Erin

middle: M

last: Baker

first: Evangelos

last: Kiskinis

first: Joseph

last: Bass

first: Robert

middle: G

last: Kalb

first: Jelena

last: Mojsilovic-Petrovic


title: Derepression of transposable elements in mouse prefrontal cortex disrupts social behavior

city: Richmond

first: Corinne

last: Smith

state: Virginia

address: 1217 E. Marshall St.

department: Anatomy and Neurobiology

institute: Virginia Commonwealth University

summary: The neurobiological origins of social behaviors are poorly understood. Previous studies have linked the function of a single Krüppel-associated box zinc finger protein (KZFP), ZFP189, in the mouse prefrontal cortex (PFC), with the regulation of transposable elements (TEs), immune genes, and social behaviors. Here, we expand the scope of inquiry to explore the relationship between collective PFC KZFP function and social behaviors by altering the function of the cognate KZFP interacting protein TRIM28 within the PFC of male and female mice. We reprogrammed natural TRIM28WT by replacing the endogenous, transcriptionally repressive domain with a synthetic, enhanced transcriptional activation domain VP64-p65-Rta (TRIM28VPR), or by excising the transcriptional regulatory domain (TRIM28NFD). Upon intra-PFC viral-mediated delivery of TRIM28 variants, we observed that inversion of TRIM28 transcriptional control via HSV-TRIM28VPR selectively produced deficits in social behaviors, without affecting non-social behaviors. RNA-sequencing of manipulated PFC revealed that HSV-TRIM28VPR drove transcriptional escape of all classes of TEs, particularly those located within intronic and enhancer regions proximal to downregulated immune genes. HSV-TRIM28VPR-mediated social deficits were reversible by intra-PFC repletion of interferon cytokines. These data point to PFC KZFP-TRIM28 interactions as necessary to stabilize genomic TEs to enable cis-regulation of key immune gene expression, which enhances organismal capacity for complex, pro-social behaviors.

overall_design: RNA-seq profiling of mouse prefrontal cortex tissue 4 days post-viral-introduction of TRIM28WT, TRIM28NFD, TRIM28VPR, or GFP transgenes.

first: R

middle: K

last: Kim

first: Natalie

last: Truby

first: Shelbey

middle: R

last: Strandberg

first: Jessica

last: Bell

first: Nic

last: Carwile

first: Gabriella

last: Silva

first: Rachael

last: Neve

first: Theingi

last: Aung

first: Xiaohong

last: Cui

first: Peter

last: Hamilton


title: AMPK agonism optimizes the in vivo activation and anti-leukemia efficacy of chimeric antigen receptor T cells

status: Public on Dec 13 2025

city: Pittsburgh

first: Amanda

middle: Catherine

last: Poholek

state: Pennsylvania

address: 4401 Penn Ave., Rangos Research Center 8129

department: Pediatrics

institute: University of Pittsburgh

summary: BACKGROUND: Chimeric antigen receptor (CAR) T cells have achieved remarkable clinical success. However, up to 50% of CAR T cell-treated leukemia patients relapse and long-term survivor data indicate that CART cell persistence is key to enforcing relapse-free survival. Unfortunately, ex vivo expansion protocols often drive metabolic and functional exhaustion, reducing in vivo efficacy. Preclinical models have demonstrated that redirecting metabolism can improve in vivo T cell function. Here, we hypothesized that exposure to an agonist targeting AMP-activated protein kinase (AMPK) would create CARTs capable of increased in vivo function and enhanced leukemia clearance. METHODS: CART cells were generated from healthy human donor T cells via lentiviral transduction, followed by exposure to either Compound 991 or DMSO for 96 hours, followed by a 48-hour washout. During and after agonist treatment, T cells were harvested for metabolic and functional assessments. To test in vivo efficacy, immunodeficient mice were injected with luciferase+ NALM6 leukemia cells, and one week later with 991- or DMSO-expanded CARTs. Leukemia burden and anti-leukemia efficacy was assessed via radiance imaging and overall survival. RESULTS: Compound 991 treatment activated AMPK without limiting cellular expansion, and increased both mitochondrial density and handling of reactive oxygen species (ROS). Mechanistically, 991 treatment mimicked nutrient starvation, with increased autophagic flux and generation of mitochondrially-protective metabolites in treated cells. Importantly, receipt of 991-exposed CARTs significantly improved in vivo leukemia clearance and prolonged recipient survival, likely as a result of elevated activation and increased CD4+ T cell yields at early times post-injection. DISCUSSION: Ex vivo expansion is necessary to generate sufficient cell numbers, but sustained activation and differentiation often negatively impact in vivo persistence and function. Here, we demonstrate that promoting AMPK activity during in vitro CART expansion metabolically reprograms cells without limiting T cell yield, increases early activation marker expression following in vivo transfer, and ultimately enhances anti-leukemia efficacy. Importantly, Compound 991 treatment achieves these results without further modifying the expansion media, changing the CART construct, or genetically altering the cells. Altogether, these data highlight AMPK agonism as a potent and readily translatable approach to improve the metabolic profile and in vivo efficacy of adoptively transferred T cells.

overall_design: 3 random human donor T cells were expanded in either Compound 991 or DMSO only control. CD4+ and CD8+ T cells were separately isolated for analysis.

first: Erica

last: Braverman

first: Craig

last: Byersdorfer

first: Poholek

last: Amanda

first: Yang

last: Aaron


title: Immunosuppressive monocytes are enriched in hepatocellular carcinoma patients with liver dysfunction in a phase II trial of combination sorafenib and nivolumab [CITE-Seq]

status: Public on Dec 12 2025

city: San Francisco

first: Bridget

middle: P

last: Keenan

state: CA

address: 505 PARNASSUS AVE

institute: University of California San Francisco

summary: Background and aims: Immune checkpoint inhibition (ICI) and anti-angiogenic therapies are active in hepatocellular carcinoma (HCC), although patients with impaired hepatic function have worse outcomes. Methods: We conducted a multi-center, open-label phase II clinical trial to assess the safety and efficacy of the multikinase inhibitor, sorafenib, combined with nivolumab, in patients with advanced or unresectable HCC and varying liver function. In a Part 1 safety lead-in, we investigated the primary endpoint of the maximum-tolerated dose (MTD) of the combination in patients with Child-Pugh A or B7 HCC. In Part 2, we enrolled patients with Child-Pugh B HCC with the primary endpoint of grade >/=3 treatment-related adverse events (TRAE) incidence. Exploratory endpoints included immunologic biomarkers. Results: Overall, 25 patients were consented and 16 eligible patients enrolled. In Part 1, dose-limiting toxicity occurred in 1 of 6 patients in Dose Level -1, and 2 of 5 patients in Dose Level 1; Dose Level -1 was determined to be the MTD. In total, 69% of patients experienced a Grade >/=3 TRAE, with similar distribution for patients with Child-Pugh A and B liver function (70%, 95% CI: 0.35, 0.93 vs 66.7%, 95% CI: 0.22, 0.96). The objective response rate was 6%. We found that patients with Child-Pugh B liver disease harbored more circulating suppressive CD14+ monocytes at baseline. Conclusions: While the combination of sorafenib and nivolumab demonstrated acceptable safety at the MTD in both Child-Pugh subgroups, the objective response rate was below the pre-specified threshold to be declared worthy of further exploration. A distinct immune cell profile in Child-Pugh B patients may define mechanisms of resistance and potential therapeutic targets in this population with unmet clinical need

overall_design: This was a single-arm, multicenter, investigator-initiated pilot study to evaluate the safety and efficacy of sorafenib and nivolumab for the treatment of patients with advanced unresectable HCC, without prior systemic therapy, with Child-Pugh A or B liver function. The study was registered at Clinicaltrials.gov as NCT#03439891. Part 1 of the pilot study was designed to first determine the maximum tolerated dose (MTD) of sorafenib in combination with nivolumab in an Escalation Cohort with 3+3 design. Due to the mid-study regulatory approvals of other combination immunotherapy regimens for patients with advanced HCC and Child-Pugh A liver function, the Part 2 Expansion Cohort of this study was amended to restrict eligibility to Child-Pugh B liver function to address the unmet clinical need in this population. Peripheral blood mononuclear cells (PBMC) were obtained from patients pre- and on-treatment for the subset of patients treated at the UCSF study site.

first: Keenan

last: Bridget P.

first: Fan

last: Zenghua

first: Le

last: Bryan Khuong

first: Harris

last: Quincy

first: Chen

last: Jocelin

first: Clark

last: Matthew

first: Lea

last: Averey

first: Zhang

last: Li

first: Cheung

last: Alexander

first: Lara

last: Frances

first: Gordan

last: John D.

first: Bracci

last: Paige

first: Behr

last: Spencer C.

first: Fong

last: Lawrence

first: Venook

last: Alan P.

first: Kim

last: Edward J.

first: Kelley

last: Robin K.


title: Comparison by microarray analysis between control and Nutlin 3b treatment in human senescent cells

city: Kyoto City

first: Takumi

last: Mikawa

address: 54 Kawaharacho, Shogoin, Sakyo-ku

department: Graduate School of Medicine

institute: Kyoto University

summary: We found that an aberrant interaction between glycolytic PGAM1 and Chk1 kinase is augmented in senescent cells. Chemical abrogation of PGAM1-Chk1 binding by Nutlin 3b blocks its interaction, followed by elimination of senescent cells, senolysis. To examine the molecular mechanism of senolysis by inhibition of PGAM1-Chk1 binding, transcriptomic analysis was performed.

overall_design: Profiles for gene expression in Ras-induced senescent IMR90 cells was measured at 48 hours with or without Nutlin 3b treatment. Three biological independent samples were prepared in each groups.

first: Hiroshi

last: Kondoh


title: Stealth replication of SARS-CoV-2 Omicron in the nasal epithelium at physiological temperature

city: Gothenburg

first: Roshan

last: Vaid

state: Västra Götalands län [SE-14]

address: Bruna Stråket 16,

department: Department of Laboratory Medicine

country: Sweden

institute: GOTEBORGS UNIVERSITET

summary: The COVID-19 pandemic was marked by successive waves of SARS-CoV-2 variants with distinct properties. The Omicron variant that emerged in late 2021 showed a major antigenic shift and rapidly spread worldwide. Since then, Omicron-derived variants have maintained their global dominance, for reasons that remain incompletely understood. We report that the original Omicron variant BA.1 evolved several traits that converged in facilitating viral spread. First, Omicron displayed an early replicative advantage over previous variants when grown in a reconstructed nasal epithelium model based on primary human cells. The increase in Omicron replication was more marked at the 33°C temperature characteristic of human nasal passages, resulting in a physiologically relevant advantage. Omicron also caused a decrease in epithelial integrity, as measured by transepithelial electrical resistance and caspase-3 activation. Furthermore, Omicron caused a more marked loss of motile cilia at 33°C than other variants, suggesting a capacity to impair mucociliary clearance. RNAseq analysis showed that Omicron induced a broad transcriptional downregulation of ciliary genes but only a limited upregulation of host innate defense genes at 33°C. The lower production of type I and type III interferons in epithelia infected by Omicron compared to those infected by the Delta variant, at 33°C as well as 37°C, confirmed the increased capacity of Omicron to evade the innate antiviral response. Thus, Omicron combined replication speed, motile cilia impairment, and limited induction of innate antiviral responses when propagated in reconstructed nasal epithelia at physiological temperature. Omicron has the capacity to propagate efficiently but stealthily in the upper respiratory tract, which likely contributed to the evolutionary success of this SARS-CoV-2 variant.

overall_design: Examination of bulk RNA-seq from Human Nasal Epithelial Cells (HNEC) infected with various SARS-CoV-2 variants at 33 ºC  and 37 ºC temperatures.

first: Barbara

middle: F

last: Fonseca

first: Rémy

last: Robinot

first: Vincent

last: Michel

first: Akram

last: Mendez

first: Samuel

last: Lebourgeois

first: Chloé

last: Chivé

first: Raphaël

last: Jeger-Madiot

first: Nikaïa

last: Smith

last: Bondet

first: Elizabeth

last: Maloney

first: Florence

last: Guivel-Benhassine

first: Olivier

last: Schwartz

first: Darragh

last: Duffy

first: Tanmoy

last: Mondal

first: Samy

last: Gobaa

first: Lisa

middle: A

last: Chakrabarti


title: Inflammation-induced lncRNA SNHG1 Orchestrates Spermatogonium Development in Non-obstructive Azoospermia via IL-17A Signaling Pathway

city: Guangzhou

first: Rui

last: Hua

state: GuangDong

address: 838 Guangzhou North Avenue

department: Department of Obstetrics and Gynecology

country: China

institute: Nanfang Hospital, Southern Medical University

summary: Non-obstructive azoospermia (NOA) is a critical subtype of male infertility associated with inflammation. However, the molecular mechanisms underlying this phenomenon remain poorly understood. This study investigated the role of the inflammation-activated long non-coding RNA SNHG1 in NOA pathogenesis. Using lipopolysaccharide (LPS)-induced orchitis mouse models and spermatogonium cell lines (GC-1 spg and TCAM-2), we observed that both SNHG1 and the transcription factor SP1 were significantly upregulated, correlating with spermatogonium proliferation and loss of stemness. Mechanistically, SP1 directly binds to and transcriptionally activates the SNHG1 promoter, whereas SNHG1 knockdown rescued LPS-induced spermatogonium dysfunction without affecting SP1 expression. RNA-seq revealed that SNHG1 overexpression activated the IL-17A signaling pathway. Notably, IL-17A receptor blockade (Brodalumab) reversed the SNHG1-mediated proliferation arrest and stemness. Our findings demonstrated that the SP1-SNHG1-IL-17A axis drives inflammatory spermatogenic failure, suggesting that IL-17A inhibition is a potential therapeutic strategy for NOA.

overall_design: RNA-seq profiling of Vector-control and SNHG1-overexpressing GC-1 spg cells at 24 hours post-transfection.

first: Yongtong

last: Zhu

first: Maocai

last: Li

first: Xiaomin

last: Zhan

first: Li

last: Liu

first: Cairong

last: Chen

first: Yao

last: Zhou

first: Pei

last: He


title: Spatial analyses of early, untreated SSc skin identify a proinflammatory vascular niche of macrophage-fibroblast signaling

city: Lebanon

first: Helen

middle: C

last: Jarnagin

state: NH

address: WTRB 6-84 1 Medical Center Drive

institute: Geisel School of Medicine

summary: Uncovering the early interactions and spatial distribution of dermal fibroblasts and immune cells in treatment-naïve diffuse cutaneous systemic sclerosis (dcSSc) patients is critical to understanding the initiating events skin fibrosis. We generated an integrated multiomic dataset of early, treatment naïve dcSSc skin. Skin biopsies were analyzed by single-nuclei multiome sequencing (snRNA-seq and snATAC-seq) and two different paired spatial transcriptomic platforms to comprehensively describe the molecular changes in these individuals. We identified a proinflammatory niche within papillary, hypodermis, and vascular niches, that are enriched for activated myeloid cells and proinflammatory fibroblasts characterized by expression of proinflammatory cytokines. Pathway analyses showed significant enrichment of PI3K-AKT-mTOR signaling pathway expression in these cellular niches, driven by profibrotic growth factor signaling networks. Macrophage subclustering showed SSc-specific macrophage activation of IL6-JAK-STAT signaling and the enrichment of oxidative phosphorylation pathways. Ligand-receptor analysis revealed that SSc macrophages secrete PDGF and TGFB to activate the inflammatory SSc-dominant fibroblast subclusters. Spatial transcriptomic analyses showed infiltrating macrophages secreted PDGF and TGFB, modulating fibroblast activation in these niches. Multiomic data integration and spatial transcriptomic neighborhood analysis showed co-localization of fibroblasts, macrophages, and T cells around the vasculature. These data suggest that interactions between activated immune cells and proinflammatory fibroblasts around vascular niches are an early event in scleroderma pathogenesis.

overall_design: 10 samples

first: Jarnagin

last: Helen

first: Whitfield

last: Michael


title: CUT&RUN in SCC-25 Parental and RARG knockout cells maps RARγ binding sites and genome wide changes in H3K4 & H3K27 trimethylation

city: New York

last: Hoxie

state: NY

address: 1300 York Avenue

department: Pharmacology

institute: Weill Cornell Medical College

type: Genome binding/occupancy profiling by high throughput sequencing

summary: Vitamin A (retinol) metabolism and signaling through nuclear retinoic acid receptors (RARs α,β,γ) regulate embryonic development, immune functions, and cell differentiation in most cell types.  RAR gamma (RARγ) is highly expressed in stratified squamous epithelial cells of the tongue, esophagus, and skin.  While data indicate that RARγ agonism is anti-tumorigenic in oral cavity squamous cell carcinoma (OCSCC), the specific, primary gene targets of RARγ remain poorly characterized. Here, we define the transcriptomic consequences of RARγ activity in OCSCC. Using a CRISPR-Cas9-mediated knockout (KO) of RARγ and pharmacological treatments with RAR agonists, we identified RARγ-specific gene targets and pathways, as well as targets that overlap with other RA-responsive nuclear receptors.

overall_design: CUT&RUN profiling of SCC-25 Parental (PAR) & RARG knockout (RARGKO) cell lines using antibodies targeting RARγ, H3K4me3, H3K27me3, and IgG. IgG is used as a negative control.

first: Xiao-Han

last: Tang

first: Lorraine

last: Gudas


title: HnRNPA2B1 tunes antimycobacterial immune responses in macrophages through alternative splicing of Irgm1

city: Nashville

first: Kristin

last: Patrick

state: Tennessee

department: Pathology, Microbiology, and Immunology (PMI)

institute: Vanderbilt University Medical Center

summary: Alternative splicing (AS) has been implicated in host responses to diverse pathogens, but our understanding of its role in Mycobacterium tuberculosis infection remains incomplete. Using RNA-sequencing and splicing-aware computational pipelines, we quantified AS in Mtb-infected bone marrow-derived macrophages (BMDMs). We found that ~5% of expressed macrophage genes exhibit one or more splicing changes at 8h post-Mtb infection, highlighting AS as a key layer of regulation in the macrophage response to intracellular pathogens. We next sought to identify RNA binding proteins that play an outsized role in shaping the macrophage transcriptome during Mtb infection. We discovered that the splicing factor hnRNPA2B1 promotes the early induction of inflammatory genes while dampening several type I interferon-stimulated genes. HnRNPA2B1 also controls alternative splicing of transcripts, notably Irgm1, a critical immunity-related GTPase. We report that the abundance of Irgm1-long, the canonical isoform, and Irgm1-short, an isoform lacking a lysosomal targeting domain is differentially regulated in response to diverse inflammatory cues. Macrophages overexpressing Irgm1-short are defective in restricting Mtb replication and accumulate LC3+ bacilli. These data highlight a key role for AS in shaping the macrophage transcriptome and pinpoint hnRNPA2B1 as a novel restriction factor in the cell-intrinsic response to Mtb.

overall_design: RNA-seq profiling of unifected and 8 hours post mycobacterium tuberculosis infected primary bone marrow derived macrophages and myeloid specifc A2B1 KO primary bone marrow derived macrophages.

first: Morgan

last: Chapman

first: Jessie

last: Huskey

first: Kaitlyn

middle: S

last: Armijo

first: Jaylen

middle: T

last: Spellman-Reliford

first: Aja

last: Coleman

first: Cory

last: Mabry

first: Stacy

last: Hahn

first: Robert

middle: O

last: Watson


title: Single-nuclei multiome and spatial analyses of early, untreated SSc skin identify a proinflammatory vascular niche of macrophage-fibroblast signaling

overall_design: Single nuclei RNA and ATAC sequencing and with paired spatial sequencing on 10 human scleroderma skin tissues and 4 control samples.

first: Michael

last: Whitfield


title: Transcriptomic changes in human SCC-25 Parental and RARG knockout cells in response to 6h and 48h treatments with RARγ agonists CD1530 or all-trans retinoic acid (RA).

overall_design: RNA-seq profiling of parental SCC-25 cells and their CRISPR-mediated RARG knockout derivative (RARGKO) with and without added ligand (1μM synthetic RARγ agonist CD1530 or 1μM endogeous ligand retinoic acid) at 6h and 48h timepoints.


title: Circulating transcriptome analysis finds gene signatures and immune cell activation and abundance predict response to immunotherapy in bladder cancer

city: Dijon

first: Romain

last: Boidot

address: 1, rue Pr Marion

country: France

institute: CGFL

summary: Background. Immune Checkpoint Blockers (ICB) have revolutionized oncology by achieving durable tumor responses in advanced cancers. Nevertheless, currently approved biomarkers (PD-L1, MSI, TMB) have suboptimal positive and negative predictive values for tumor response and survival. Patients and Methods. We aimed to assess the value of RNA sequencing from circulating blood, a new type of liquid biopsy, to predict responses to ICB. We performed total paired-end RNA sequencing at 20 million reads and analyzed differential gene expression, signaling pathway activation, and immune cell abundances according to cancer outcomes. The analysis was conducted on baseline frozen whole blood samples from 164 patients prospectively enrolled in the IOPREDI study. Results. We found that some immune-related genes and signaling pathways were highly expressed in patients who achieved a durable clinical benefit. Furthermore, analyses of both progression-free survival (PFS) and overall survival (OS) confirmed significantly higher expression levels of immune-related signaling pathways in long-term survivors. Gene expression signatures capable of classifying patients based on clinical response or PFS were also identified. Interestingly, deconvolution analysis revealed a significant higher abundance of resting NK cells in patients with prolonged PFS or OS, in contrast to other cytotoxic cell types. Finally, high expression of the CST7 gene and increased abundance of naïve B lymphocytes were associated with immune-related adverse events (irAEs). Conclusion. Total RNA sequencing from whole blood provides high-quality data to predict clinical response, survival, and occurrence of irAEs. The use of this liquid biopsy prior to immune checkpoint blockage could improve treatment efficacy and irAEs management.

overall_design: Whole bloods from 164 patients with urinary tract cancer were collected on EDTA tubes. After RNA extraction, total RNAseq was performed and obtained results were used for statistical analysis with different clinical parameters such as clinical response, progression free and overall survivals, and immune related adverse events.

first: Sandy

last: Chevrier

first: Corentin

last: Richard


title: Z-DNA formation induces the totipotent-like state and primes Zscan4-dependent chromatin compartmentalization

status: Public on Dec 11 2025

city: Paris

first: Yann

last: Loe-Mie

address: 25 rue du Dr Roux

department: Computational Biology

institute: Institut Pasteur

type: Methylation profiling by high throughput sequencing

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

sample_organism:
Homo sapiens
Mus musculus

platform_organism:
Homo sapiens
Mus musculus

overall_design: Refer to individual Series


title: Müller cell glutamine metabolism links photoreceptor and endothelial injury in diabetic retinopathy

status: Public on Dec 10 2025

first: Katia

last: Corano Scheri

address: 300 E. Superior St.

department: Ophthalmology, Feinberg School of Medicine

summary: We characterized the timeline of molecular dysfunction in diabetic retinopathy (DR) and diabetic retinal disease (DRD) by studying the streptozotocin (STZ)-induced mouse retina over the course of 6 months of diabetes. We performed bulk RNA-Seq on endothelial and retinal cells, separately, at 1, 3 and 6 months of diabetes and single-cell RNA-Seq (scRNA-Seq) at 3 months. Transcriptomic changes were validated by in vitro, and ex vivo assays and immunohistochemistry of mouse and human tissue. Bulk RNA-Seq revealed inflammation in endothelial cells at 1 month. At 3 months, scRNA-Seq identified glutamine-driven anaplerotic dysfunction in Müller cells, confirmed by retinal culture. We posited this glutamine deficiency would impact the photoreceptors and endothelial cells. We validated this hypothesis using endothelial cells in vitro, and immunohistochemistry of disrupted photoreceptor ribbon synapses in mouse and human diabetic retinas. Additionally, glutamine deprivation increased expression of apoptotic genes in endothelial cells. At 6 months, we observed significant downregulation of angiogenic pathways and elevated profibrotic markers. Our results suggest that dysfunction of the metabolic ecosystem linking the Müller-photoreceptor-endothelial cells is central to the early stages of DRD pathogenesis, impacting photoreceptor synapses and endothelial cells, before the appearance of the classic microvascular features of DR.

overall_design: Bulk RNA-seq on endothelial and retinal cells (analyzed separately) from sham and STZ-diabetic mice at 1, 3, and 6 months of diabetes, and single-cell RNA-seq at 3 months of diabetes (sham vs. STZ)

first: Yi-Wen

last: Hsieh

first: Thomas

last: Tedeschi

first: James

last: Hurley

first: Amani

last: Fawzi


title: Gene expression analysis of non-clear-cell renal cell carcinoma and clear-cell renal cell carcinoma kidney cancers

city: Tokyo

first: Yu-Yu

last: Liu

address: 2-4-41 Ebara, Shinagawa-ku

institute: Hoshi University

summary: Data regarding the clinical outcomes of immune checkpoint inhibitor (ICI) therapy and profiles of the tumor immune microenvironment (TIME) in non-clear-cell renal cell carcinoma (nccRCC) remain limited. Here, we retrospectively compared the effectiveness profiles of first-line ICI combination therapy between patients with clear-cell RCC (ccRCC) and those with nccRCC.

overall_design:
RNA-seq of non-clear-cell renal cell carcinoma and clear-cell renal cell carcinoma kidney cancers
Please note that cancer subtype information is provided in the "tissue" field. The  treatment details and clinical outcomes of ICI therapy are presented in the associated publication.

first: Hiroki

last: Ishihara

first: Hironori

last: Fukuda


title: Nuclear Phase Separation drives Acute Myeloid Leukemia

city: HOUSTON

first: Margaret

last: Goodell

state: TX

address: 1 Baylor Plz, Rm N1030

institute: Baylor College of Medicine

summary: To investigate how nuclear condensates formed by NPM1c coordinate protein recruitment and promote chromatin binding in leukemia

overall_design:
We assessed chromatin binding of XPO1. NUP98, KMT2A, and MENIN in the context of NPM1c degradation, XPO1 inhibition, or MENIN inhibition using Cut-and-run sequencing
Using an established OCI-AML3 cell line expressing an inducible degradation platform for NPM1c, we treated cells for 24hrs with dTAG-13, Eltanexor, or VTP50469 and performed Cut-and-run sequencing

first: Gandhar

last: Datar

first: Chun-Wei

last: Chen

first: Joshua

last: Riback


title: Heat-Shock Pathway Activation by TRC-051384 Protects Spiral Ganglion Neurons from Noise-Induced Hearing Loss [RNA-Seq]

first: Jeffrey

last: Savas

state: Illinois

address: 303 E. Chicago Avenue, Ward 12-013

department: Neurology

summary: Noise-induced hearing loss (NIHL) is a major public health problem caused by damage to cochlear hair cells, synapses, and spiral ganglion neurons (SGNs). However, effective treatments are completely lacking. We investigated cellular stress responses induced by loud noise in a mouse model of cochlear synaptopathy and tested whether selective activation of the dominant pathway identified could confer protection. RNA sequencing and spatial transcriptomics revealed that noise exposure elicited a robust but transient upregulation of endoplasmic reticulum chaperones and proteasome subunits in SGNs and supporting cells. To target this response, we administered TRC051384, a small-molecule activator of the heat shock transcription factor Hsf1, prior to noise exposure. TRC051384 crossed the blood–labyrinth barrier and reached the cochlea, induced heat shock protein gene expression, and restored ubiquitin–proteasome function in SGNs. Notably, TRC051384 treatment improved auditory brainstem response recovery, preserved Wave I amplitudes, and maintained ribbon synapse density. These findings establish proteotoxic stress in SGNs as a central driver of NIHL and identify HSF1 activation as a promising therapeutic strategy.

overall_design: Bulk RNA-seq was performed on cochlear tissue from 16-week-old CBA/CaJ mice subjected to acoustic overexposure. Mice were divided into four groups (N = 3 per group): Control – mock-exposed (no noise). Noise-exposed, 0 hr – exposed to 2 hours of 100 dB SPL broadband noise and sacrificed immediately after exposure. Noise-exposed, 2 hr – sacrificed 2 hours post-exposure. Noise-exposed, 4 hr – sacrificed 4 hours post-exposure. Noise-exposed, 8 hr – sacrificed 8 hours post-exposure.

middle: N

first: Seby

last: Edassery

first: Miguel

last: Ramirez


title: HIV-1 Infection Regulates Gene Expression by Altering Alternative Polyadenylation Through CPSF6 and CPSF5 Delocalization

city: Rochester

first: Eric

middle: John

last: Wagner

address: 575 Elmwood Avenue

department: Biochemistry and Biophysics

institute: University of Rochester Medical Center

summary: HIV-1 viral core transport to the nucleus, an early infection event, triggers cleavage and polyadenylation specificity factor (CPSF)5 and CPSF6 to translocate from paraspeckles to nuclear speckles, forming puncta-like structures. CPSF5 and CPSF6 regulate alternative polyadenylation (APA), which governs approximately 70% of gene expression. APA alters the lengths of mRNA 3’-untranslated regions (3’-UTRs), which contain regulatory signals influencing RNA stability, localization, and function. We investigated whether HIV-1 infection–induced changes in CPSF5 and CPSF6 subcellular localization are accompanied by changes in cellular function. Using two independent methodologies to assess APA in human primary CD4+ T cells and cell lines, we found that HIV-1 infection regulates APA, dependent on the interaction of CPSF6 with the viral capsid, recapitulating the APA phenotype observed in CPSF6 knockout cells. Our study demonstrates that HIV-1 infection leverages the interaction between the viral capsid and CPSF6 to co-opt cellular processes, alter gene expression, and drive pathogenesis.

overall_design: PAC-Seq profiling was employed to map global mRNA 3’-end changes in HIV-1–infected and mock-infected A549 cells

first: Charlotte

last: Luchsinger

first: Annie

last: Dai

first: Aiswarya

last: Balakrishnan

first: Cinzia

last: Bertelli

first: Bin

last: Cui

first: Ramon

last: Redondo

first: Felipe

last: Diaz-Griffero


title: Surgical revision of S. aureus infection increases virulence factor expression and activates a multi-tissue inflammatory response

city: Philadelphia

first: Theresa

last: Freeman

state: PA

address: 1015 Walnut Street

department: Orthopedic Surgery Research

institute: Thomas Jefferson University

summary: Surgical revision of infection can involve multiple procedures. Each revision activates a tissue injury response and disrupts the established bacterial biofilm. However, it is not well understood how the bacteria, immune system, and overall tissue environment coordinate their response to revision. Our results show that immunological niches already compromised by infection – such as the bone marrow, lymph nodes, and circulating blood – further upregulate pro-inflammatory programs in response to revision surgery. This enhanced inflammation at the incision site has no effect on reducing bacteria numbers. Instead, it leads to increased expression of virulence factors, enhanced tissue remodeling, and damage including bone osteolysis and muscle fibrosis. Whereas muscle fibrosis appears to resolve 14 days post-revision, osteolysis continues to progress. These findings show that revision surgery negatively impacts all tissues within the surgical site. It is therefore essential to question the risks and benefits of each revision on a case-by-case basis. Further, understanding the timing and tissue changes associated with revision of infected orthopedic sites will help inform the design of additional interventions to minimize tissue damage and maximize bactericidal effects.

overall_design: Gene expression was compared between uninfected and infected surgical incisions in Sprague-Dawley rats at a pre-revision surgery timepoint and between infected pre-revision rats and infected rats at three different timepoints (6 hours, 4 days, and 14 days post-revision). An index surgery created an initial incision, and revision surgery (and the pre-revision surgery timepoint) occurred 7 days after index. The rats were euthanized either pre-revision (7 days post index), 6 hours post-revision (7 days + 6 hours post-index), 4 days post-revision (11 days post-index), or 14 days post-revision (21 days post-index). The biceps femoris muscle was excised on the day of euthanasia for each rat and snap frozen. RNA was extracted from the snap-frozen muscle and sequenced at Novogene.

first: Carly

last: Smith

first: Arianna

last: Moniodes

first: Amanda

last: Watkins

first: Autumn

last: Melvage

first: Thomas

last: Thompson

first: Eirene

last: Choi

first: Abigail

last: Lucas

first: Brendan

last: Gilmore

last: Schaer

first: Noreen

last: Hickok


title: scRNA-seq of a knockout village during hPSC-derived islet differentiation

city: Washington

first: Bicna

last: Song

state: DC

address: 7144 13th Pl NW

institute: Children's National Hospital

summary: This submission consists of processed single-cell RNA-seq data of knockout village samples, provided as filtered feature–barcode matrices generated using Cell Ranger v7.1.0 with default parameters. We previously deposited the same biological samples and data processed by STAR under GEO accession GSE288587. The corresponding raw FASTQ files are available in ENA under accession ERP168459. The supplementary file (reanalysis_samples.xlsx) provides a reference table linking each sample in this submission to its corresponding GSM in GSE288587, which contains the detailed experimental descriptions of culture information, genotypes, and differentiation stages.

relation:
Reanalysis of: GSM8770302
Reanalysis of: GSM8770313
Reanalysis of: GSM8770303
Reanalysis of: GSM8770314
Reanalysis of: GSM8770304
Reanalysis of: GSM8770315
Reanalysis of: GSM8770305
Reanalysis of: GSM8770316
Reanalysis of: GSM8770306
Reanalysis of: GSM8770317
Reanalysis of: GSM8770307
Reanalysis of: GSM8770318
Reanalysis of: GSM8770308
Reanalysis of: GSM8770319
Reanalysis of: GSM8770309
Reanalysis of: GSM8770320
Reanalysis of: GSM8770310
Reanalysis of: GSM8770321
Reanalysis of: GSM8770311
Reanalysis of: GSM8770322
Reanalysis of: GSM8770312
Reanalysis of: GSM8770323
SubSeries of: GSE315753

overall_design: The knockout village consist of 3 WT and 76 knockout lines targeting 30 pancreas developmental regulators and diabetes genes, including GATA6, PDX1, GATA4, FOXA1, FOXA2, MNX1, NEUROD1, NKX2-2, RFX6, GSC, HHEX, HNF4A, PAX6, PBX1, GLIS3, NEUROG3, ARX, OTUD5, BMPR1A, TLE3, BCOR, QSER1, TET1, TET2, TET3, TADA2B, KDM2B, PROSER1, ONECUT1, and NANOG. Edited lines were generated in two hPSC backgrounds (HUES8 and H1). Individual clonal lines were uniquely barcoded by lentiviral infection with GFP-barcode plasmids from the LARRY library and pooled to form a knockout village for differentiation. Samples were collected at five differentiation stages: day -1 (hPSC, 1 day prior differentiation), day 3 (definitive endoderm, DE), day 7 (posterior foregut, PFG), day 11 (pancreatic progenitor, PP) and day 18 (early SC-islet). In addition, WT cells in H1 and HUES8 backgrounds were differentiated and sequenced in parallel at 17 time points: day -1 (hPSC), 3, 5, 7, 9, 10, 11, 12, 13, 14, 15, 16, 18, 21, 25, 26, 35.

first: Dingyu

last: Liu

first: Dapeng

last: Yang

first: Renhe

last: Luo

first: Wei

last: Li

first: Danwei

last: Huangfu


title: Modeling the chondrocyte-derived osteoblasts formation process reveals its molecular signature and regulation network

city: Muenster

first: Marcos

last: Araúzo-Bravo

address: Rontgenstr. 20

department: Cell and Developmental Biology

country: Germany

institute: Max Planck Institute for Molecular Biomedicine

summary: Endochondral ossification is a physiological process related to the development of long bones, not only on the embryo phase, but also during postnatal development. Mouse cell lineage tracking studies and histology techniques focused on the metaphysis and growth plate area of long bones have described a phenotype transition from chondrocytes to bone cells. However, the molecular events involved in this phenotype transition is still undescribed. Aiming to reproduce this phenotype transition in in vitro cell culture context, primary mesenchymal progenitor cells have been isolated from femur heads, characterized, and cultured following a serial differentiation protocol, first using chondrogenic media and then osteogenic media. RNA samples were obtained at different cell culture time points and processed for RNAseq studies. Time points are: D7 corresponding to 7 days culture in chondrogenic media, D8 corresponding to samples obtained one day after switching to osteogenic media, D10 corresponding to samples obtained three days after switching to osteogenic media, and, D28 corresponding to samples obtained osteogenic terminal end point, compiling 7 days in chondrogenic media and 21 days in osteogenic media.

overall_design: The data D7 (D7), is performed with 3 replicates. The data D8 (D8), is performed with 3 replicates. The data D10 (D10), is performed with 3 replicates. The data D28 (D28), is performed with 3 replicates.

first: Raquel

last: Ruiz-Hernández

first: Amaia

last: Vilas-Zornoza

first: Felipe

last: Prosper

first: María

last: Caffarel

first: Daniela

last: Gerovska

first: Ander

last: Abarrategi


title: Whole transcriptome analysis in obstetric antiphospholipid syndrome

status: Public on Dec 08 2025

city: Jinan

first: Lan

last: Zhang

address: jingsi

institute: Shandong University

summary: This study aims to investigate the expression profiles of coding and non-coding RNA in OAPS, thereby deepening our understanding of the potential mechanisms of OAPS. Plasma samples were collected from 3 OAPS patients and 3 healthy controls. Then, exosomes were separated by differential ultracentrifugation. The transcriptome of purified exosomes was comprehensively analyzed using the Illumina sequencing platform. Exosomal messenger RNA (mRNA), long non-coding RNA (lncRNA), and circular RNA (circRNA) were identified using a threshold of |log2 (fold change)| ≥ 1 and P < 0.05.


title: CFTR mutation abrogates Prevotella regulation of epithelial cell defense against Staphylococcus aureus

status: Public on Dec 09 2025

city: Aurora

first: Sarah

middle: E

last: Clark

state: CO

address: 12700 E 19th Ave, Mail Stop 8333

institute: University of Colorado School of Medicine

summary: Background: The oral anaerobe Prevotella melaninogenica is enriched in the lungs of people with cystic fibrosis (pwCF), yet its functional impact on respiratory tract homeostasis remains incompletely understood. Prior studies identified immune modulatory effects following lung exposure to Prevotella, but the relevance of these findings for CF infections is unknown.  Methods: The impact of P. melaninogenica on infection with the CF pathogen Staphylococcus aureus was evaluated using a mouse lung infection model and human respiratory tract cystic fibrosis transmembrane conductance regulator (CFTR) mutant and isogenic wild-type (WT)-corrected CFBE41o- epithelial cells. RNA-sequencing was performed to compare Prevotella-induced signaling programs in WT-corrected versus CFTR mutant cells.  Results: P. melaninogenica significantly reduced S. aureus lung infection, which was associated with elevated S. aureus killing by lung neutrophils and impaired S. aureus adherence to epithelial cells. Live or heat-killed Prevotella were sufficient to mediate these effects, which were dependent on the toll-like receptor TLR2. Prevotella impairment of S. aureus adherence also required CFTR function, as this effect was lost in CFTR mutant cells but restored by CFTR modulator therapy. RNA-sequencing identified several antibacterial defense pathways selectively upregulated by Prevotella in WT corrected epithelial cells, correlating with higher IL-8 and IL-6 cytokine production.  Conclusions: P. melaninogenica enhanced neutrophil and epithelial defense against S. aureus, but these benefits were lost with CFTR dysfunction. CFTR modulator therapy rescued Prevotella responsiveness in respiratory epithelial cells, highlighting the potential for synergistic effects of host-microbiome interactions and CFTR targeted therapies.

overall_design: CFBE41o- CFTR mutant and isogenic WT corrected CFBE41o- epithelial cells in submerged culture were either untreated or treated with heat-killed Prevotella melaninogenica for 24 hours. The experiment is designed to capture the CFTR-dependent gene expression changes in unstimulated and Prevotella stimulated cells.

first: Maksym

last: Goryachok

first: Ana

last: Fairbanks-Mahnke

first: Samantha

last: Fulte

first: Emily

last: Tamkin

first: Arianna

last: McCarty

first: Eric

middle: D

last: Larson

first: Paul

last: Planet


title: Histone H3K4 methylation regulation and three-dimensional aggregating distribution of a subset of genomic loci mediated by CHD3 homolog PKL in Arabidopsis [Hi-C]

city: Beijing

first: Mengfei

last: Song

state: Beijing

address: 北京市海淀区颐和园路5号

institute: Peking university

summary: Arabidopsis PICKLE (PKL) is a putative CHD3-type chromatin remodeling factor. Despite its importance in environmental stimulus responses and plant development, how PKL is recruited to target gene loci and its detailed regulatory role in controlling target gene chromatin states is not fully understood. Here, we report genome-wide evidence for the recruitment of PKL by specific transcription factors, establish the molecular connection between PKL and H3K4me2/3, and demonstrate PKL is essential for the space-clustering distribution of its target genes. We captured the genome-wide binding sites of PKL by ChIP-seq using endogenous antibody. Further analyses gave evidence that plant-specific transcriptional factors containing TCPs, PIFs, and HY5, play dominant role in recruiting PKL to its target gene loci in Arabidopsis thaliana. The chromatin of PKL target genes showed significantly enriched depositions of H3K4me2 and H3K4me3. PKL directly interacted with the COMPASS complex scaffold protein WDR5A. It seems that PKL acts through WDR5A to stabilize the highly accumulated levels of H3K4me2 at specific euchromatic loci. Strikingly, PKL-bound genes distributed space-contiguously, the manner of which is dependent on PKL and PKL-interacted TFs. Moreover, the working model of PKL we proposed in this study is likely conserved in liverwort and rice. PKL associates with specific gene loci by interacting with specific transcription factors and promotes H3K4me2 depositions locally. Meanwhile, PKL acts as a hub mediating its target gene loci spatial-aggregation. PKL and its homologs in rice and liverwort might display similar molecular functions

overall_design: Three biological replicates of each genotype were used for high-throughput sequencing analysis. All experiments wer conducted using  9-day-old seedlings grown in continuous white light.

first: Yuqiu

last: Wang

first: XingWang

last: Deng

first: Danmeng

last: Zhu


title: Histone H3K4 methylation regulation and three-dimensional aggregating distribution of a subset of genomic loci mediated by CHD3 homolog PKL in Arabidopsis [RNA-Seq]

address: 北京市海淀区颐和园路5号

overall_design: Three biological replicates of each genotype were used for high-throughput sequencing analysis. All experiments wer conducted using  14-day-old seedlings grown in at 25°C (12h light/12h dark).


title: The single cell landscape of the human vein after arteriovenous fistula creation and implications for maturation failure.

city: Miami

first: Anthony

last: Griswold

state: FL

address: 1501 NW 10th Ave, BRB 318

institute: University of Miami

summary: We performed single-cell RNA sequencing of venous samples from 20 patients, including 6 pre-access veins, 2 early AVF resections, and 12 second-stage AVFs that matured (6) or failed (6).

overall_design: Vessels were collected in cold cell culture media and enzymatically digested to generate single-cell suspensions. Samples were run using the Chromium Single Cell 3′ Library & Gel Bead Kit v3 (10X Genomics) with a target capture of 10,000 cells. Libraries were sequenced on the Illumina NovaSeq 6000/X Plus. FASTQ files were generated with Cell Ranger's mkfastq pipeline (version 6.0.2). The Cell Ranger's count pipeline (version 6.0.2) was used to generate raw gene-barcode matrices from alignment to the 10X Genomics pre-built Cell Ranger human reference package (version 2020-A), from GRCh38 Ensembl build 98/GENCODE v32 gene annotations.

first: Laisel

last: Martinez

first: Roberto

middle: I

last: Vazquez-Padron

middle: J


title: Spatial transcriptomic profiling of human lung tissue in chronic obstructive pulmonary disease (COPD) [Xenium]

city: New Haven

first: Maor

last: Sauler

state: CT

address: 300 Cedar Street

department: Section of Pulmonary, Critical Care, and Sleep Medicine

institute: Yale School of Medicine

summary: To spatially contextualize and extend disease-associated cellular states, we generated Xenium spatial transcriptomics data from FFPE lung tissue of 38 participants spanning the COPD disease spectrum. Four tissue microarrays (TMA1–TMA4) were profiled using a custom 480-gene Xenium panel. These data capture the in situ organization of inflammatory, regenerative, and remodeling cell states and reveal spatially localized niches and patterns of cell–cell communications relevant to COPD pathology. This dataset provides high-resolution spatial context for characterizing microenvironmental structure and cell–cell interactions in COPD lung tissue.

overall_design: FFPE lung tissue from 38 participants across the COPD spectrum was organized into four tissue microarrays (TMA1–TMA4), comprising 99 total cores that sampled parenchymal, airway, and vascular regions. Sections (5 µm) from each TMA were mounted on Xenium slides and processed according to the 10x Genomics FFPE workflow (CG000578, Rev C) using a custom 480-gene probe panel (hLung_480g, design ID EM2BNX, v1.0.0). The workflow included deparaffinization, decrosslinking, RNA release, in situ probe hybridization, signal amplification, and multimodal staining. Each slide was imaged and decoded on the Xenium Analyzer to produce cell-resolved transcript and morphology data.

first: Yuening

first: Huanhuan

last: Wei

first: Jessica

last: Nouws


title: Genome-wide tongue epithelia transcriptomic profiles from K14-rtTA;TRE-FLBmi-1 + 4-nitroquinoline 1-oxide (4-NQO), 25 weeks (KrTB-N (25w)), KrTB+Doxycycline+4-NQO, 4 weeks (KrTB-DN (4w)), and KrTB+Doxycycline+4-NQO, 10 weeks (KrTB-DN (10w)).

city: New York City

first: Jorge

last: Baquero

summary: We developed a transgenic mouse model (truncated K14-rtTA; TRE/Bmi1, KrTB) containing a doxycycline- (dox) controlled, Tet-responsive element system to selectively overexpress BMI1 only in the basal epithelial stem cells (SCs) of the tongue. Here we used this transgenic mouse line to delineate BMI1 actions in early-stage oral squamous cell carcinoma (OSCC). We observed more oncogenic changes in mice with ectopic BMI1 expression after 4 weeks of 4-nitroquinoline 1-oxide (4-NQO) treatment. We detected increased proliferation and oxidative stress, as well as increased expression of multiple transcripts and proteins linked to human OSCCs, in murine tongue epithelia with high BMI1 expression during early carcinogen-induced tumorigenesis. Furthermore, increases in mRNAs encoding multiple metabolic targets, such as SLC16A3, PKM, and GPI1, were accelerated upon BMI1 overexpression in our 4-NQO model.

overall_design:
Examination of genome-wide transcript levels in mouse tongue epithelia samples. 12 samples were analyzed, 4 biological replicates per condition (KrTB-DN (4w) vs. KrTB-N (25w) and KrTB-DN (10w) vs. KrTB-N (25w)).

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

first: Xiao-Han

last: Tang

first: Daniel

last: Galke

first: Theresa

last: Scognamiglio

first: Tuo

last: Zhang

first: Lorraine

last: Gudas


title: Single-nucleus RNA-seq reveals reprogrammed hepatocytes that express c-Met/β-catenin oncogenes in LPD-fed mice.

city: New Brunswick

first: Xinlu

last: Han

address: 164 Frelinghuysen Road Piscataway

institute: Rutgers university

summary: To further interrogate the impact of low protein diet (LPD) on the c-Met/β-catenin expressing hepatocytes, we performed single-nucleus RNA-sequencing (snRNA-seq) analysis. Mice were fed on chow diet (CD) or LPD for one week, followed by SB-HTVI of c-Met/β-catenin. Two weeks post SBHTVI, 42,277 single nuclei were sequenced with 12,413 in the CD-vector control, 10,225 in CD c-Met/β-cat, 9,707 in LPD-vector control, and 9,932 in LPD c-Met/β-cat.

overall_design: Bl/6 mice were fed with CD or LPD for one week, then injected with c-Met/β-catenin plasmids via SB-HTVI, and kept on the same diets for two more weeks.

first: Jiekun

last: Yang

first: Junrong

last: Yan


title: Single-nucleus and spatial transcriptomic profiling of human lung tissue in chronic obstructive pulmonary disease (COPD)


title: Bulk RNA-seq of the CD and LPD-fed mice injected with vector control or c-Met/ΔN90-β-catenin by SB-HTVI

summary: We performed bulk RNA-seq to compare liver tissues from 4 groups of mice: vector control fed with CD, c-Met/β-cat mice fed with CD, vector control fed with LPD, and c- Met/β-cat mice fed with LPD. Differential gene expression and gene set enrichment analyses (GSEA) were performed and identified two clusters that might help explain the differential tumor development in the CD and LPD groups.

overall_design: Vec and c-Met/ΔN90-β-catenin fed with CD or LPD (n=3 in each group) were harvested at the endpoint of the CD-fed c-Met/ΔN90-β-catenin mice.

first: Zong

last: Wei-Xing

first: Shen

last: Jianliang

first: Yan

last: Junrong


title: Bulk liver tissue RNA-seq was performed using the vector control livers and that with c-Met/ΔN90-β-catenin SB-HTVI for 2 and 3 weeks

summary: Bulk RNA-seq of the liver tissues at early time points after c-Met/β-catenin expression (2 and 3 weeks) showed changes of gene expression of cell growth/migration, carbohydrate metabolism, and lipid metabolism.

overall_design: Seven-week-old GS WT male mice were injected with vehicle or c-Met/ΔN90-β-catenin/SB10 plasmids, and livers were harvested 0, 2 or 3 weeks after the injection for RNA-sequencing analysis.


title: High-resolution HIV-1 m6A epitranscriptome reveals splicing-dependent methylation clusters and unique 2-LTR transcript modifications

status: Public on Dec 05 2025

city: Gif sur Yvette

first: Delphine

last: Naquin

address: avenue de la terrasse

institute: CNRS

summary: The N6-methyladenosine (m6A) modification of HIV-1 RNAs plays essential roles in regulating viral infection. This modification has been extensively studied but due to a lack of precision of the detection methods, the number and precise positions of m6A sites remain unclear. Here, using the latest Nanopore chemistry and direct m6A base-calling option, we identify 18 m6As among which 14 are located in the 3’ genome extremity and four in central regions. In addition, our data show that these positions are differently methylated among splicing isoforms. Among these sites, eleven are clustered in two short segments (197 nt and 43 nt) presenting peak-shaped methylation profiles. Single molecule analysis reveals a very small number of transcripts which are unmethylated in both clusters (≤ 1.5% of spliced transcripts and ≤ 5.4% of unspliced viral RNA). We also identify a ~732 nt RNA species resulting from the transcription of non-integrated viral DNA circles closed by two long terminal repeats (2-LTR circles). These transcripts start in the first LTR and terminate at the polyA site of the second LTR and harbour six m6A sites. Five of them are shared with the other transcripts and remarkably, they present the highest methylation rates. The sixth site is uniquely methylated in this transcript suggesting that this RNA plays a function in HIV-1 infection. Together, these results reveal a new landscape of HIV m6A transcriptome modifications and open the route to decipher their role in the viral life cycle.

overall_design: CD4+ T and supT1 cells infected by the virus HIV NL4-3 XCS. Cells are harvested 20h, 30h post-infection for SupT1 cells and 48h and 72h for CD4+ T cells. Two independant infections have been done, which were sequenced in duplicate for supT1.

first: Sandra

last: Blanchet

first: Erwin

last: vanDijk

first: Lisa

last: Bertrand

first: Sylvie

last: Grégoire

first: Cécilia

last: Bertha Ramirez

first: Rania

last: Ouazahrou

last: Jaszczyszyn

first: Arnaud

last: Moris

first: Claude

last: Thermes

first: Céline

last: Hernandez

first: Olivier

last: Namy


title: Histone H3K4 methylation regulation and three-dimensional aggregating distribution of a subset of genomic loci mediated by CHD3 homolog PKL in Arabidopsis [9-day-old seedlings, RNA-Seq]

first: Mengfei

last: Song

address: 北京市海淀区颐和园路5号

first: Yuqiu

last: Wang

first: XingWang

last: Deng

first: Danmeng

last: Zhu


title: Histone H3K4 methylation regulation and three-dimensional aggregating distribution of a subset of genomic loci mediated by CHD3 homolog PKL in Arabidopsis

address: 北京市海淀区颐和园路5号

first: Xing

middle: W


title: Heat-Shock Pathway Activation by TRC-051384 Protects Spiral Ganglion Neurons from Noise-Induced Hearing Loss [Spatial Transcriptomics]

city: Chicago

first: Jeffrey

last: Savas

institute: Northwestern University

overall_design: Spatial transcriptomics using GeoMx was performed on cochlear tissue from 16-week-old CBA/CaJ mice subjected to acoustic overexposure. Mice were divided into two groups (N = 5 per groups): Control – mock-exposed (no noise). Noise-exposed,2 hours of 100 dB SPL broadband noise and sacrificed immediately after exposure.

first: Seby

last: Edassery

first: Miguel

last: Ramirez


title: Differential Transcriptome Features of Peripheral Blood Mononuclear Cells in Pulmonary Sarcoidosis with and without Extrapulmonary Lesions

city: Chiba

first: Takeshi

last: Kawasaki

address: 1-8-1, Inohana, Chuoku

department: Respirology

institute: Chiba University

summary: Sarcoidosis is a systemic granulomatous disease of unknown etiology. Pulmonary sarcoidosis with extrapulmonary lesions (EPL), especially in cardiac sarcoidosis, is associated with poor prognosis. The transcriptome features of peripheral blood mononuclear cells (PBMCs) could be crucial in sarcoidosis pathogenesis. However, the gene expression characteristics associated with EPL development in pulmonary sarcoidosis remain unknown. Therefore, we investigated gene expression patterns associated with the development of EPL in pulmonary sarcoidosis. First, we conducted trascriptome analysis between patients with pulmonary sarcoidosis and healthy controls. Principal component analysis (PCA) revealed a clear distinction between them, with 227 differentially expressed genes detected. Enrichment analysis revealed upregulated immunological pathways related to granuloma formation in pulmonary sarcoidosis PBMCs, including T helper 17 and tumor necrosis factor-alpha signaling pathways, inflammatory cytokine production, and response to external stimuli. Furtheremore, PCA differentiated patients with pulmonary sarcoidosis with and without EPL, and 206 differentially expressed genes identified, including interferon-gamma (IFNG) and interferon lambda receptor 1 (IFNLR1). Gene ontology (GO) analysis revealed that interleukin 6 (IL-6) and IL-23 production were upregulated in patients with pulmonary sarcoidosis and EPL. In cardiac sarcoidosis, nitric oxide synthases (NOS), including NOS1 and NOS2, were upregulated in PBMCs. The current study strengthens our understanding of the mechanisms underlying granuloma formation in sarcoidosis and demonstrates the differential transcriptome features of PBMCs in patients with pulmonary sarcoidosis with and without EPL, highlighting IFNG and IFNLR1 upregulation. The upregulation of these genes may be related to EPL development and could serve as potential therapeutic targets for sarcoidosis.

overall_design: To investigate the pathogenesis of pulmonary sarcoidosis in PBMCs, we compared patients with pulmonary sarcoidosis (n=14) and healthy controls (n=26) samples by RNA-seq. Then, to investigate the pathogenesis of pulmonary sarcoidosis with extrapulmonary lesions (EPL), we compared samples between pulmonary sarcoidosis with EPL (n=9) and without EPL (n=5), respectively, by RNA-seq.

first: Yushi

last: Murai

first: Takuro

last: Imamoto

first: Daisuke

last: Ishii

first: Keiichiro

last: Yoshioka

first: Yoshinori

last: Hasegawa

first: Osamu

last: Ohara

first: Koichiro

last: Tastumi

first: Takuji

last: Suzuki


title: The G3BP Stress-Granule Proteins Reinforce the Translation Program of the Integrated Stress Response

city: Boston

first: Jarrett

last: Smith

state: MA

address: 455 Main st, Room 627

institute: Whitehead Institute

summary: When mammalian cells are exposed to extracellular stress, they coordinate the condensation of stress granules (SGs) through the action of key nucleating proteins G3BP1 and G3BP2 (G3BPs) and, simultaneously, undergo a massive reduction in translation. Although SGs and G3BPs have been linked to this translation response, their overall impact has been unclear. Here, we investigate the longstanding question of how, and indeed whether, G3BPs and SGs shape the stress translation response. We find that SGs are enriched for mRNAs that are resistant to the stress-induced translation shutdown. Although the accurate recruitment of these stress-resistant mRNAs does require the context of stress, a combination of optogenetic tools and spike-normalized ribosome profiling demonstrates that G3BPs and SGs are necessary and sufficient to both help prioritize the translation of their enriched mRNAs and help suppress cytosolic translation. Together these results support a model in which G3BPs and SGs reinforce the stress translation program by prioritizing the translation of their resident mRNAs.

overall_design: Ribo-seq and RNA-seq were performed on replicate samples from HCT116 cells treated with 500 uM sodium arsenite for 1 hour, heat shocked at 45C for 25 min, depleted of their endogenous G3BPs using Auxin induced degrons, or that had  SGs, OGs, or SOGs, purified from them and were subsequently sequeneced.

first: David

last: Bartel


title: Targeted PDGFRα+ fibroblast ablation exacerbates pathologic features of asthma in house dust mite-induced allergenic asthma model

city: Honolulu

first: Juwon

last: Park

state: HI

address: 651 Ilalo St.

department: Tropical Medicine, Medical Microbiology and Pharmacology

institute: University of Hawaii at Manoa

summary: This study demonstrates the consequence of PDGFRα+ fibroblast ablation in adult lung homeostasis in both steady-state and asthmatic conditions. Our study highlight that the essential roles of PDGFRα+ fibroblast in maintaining immune balance, ECM integrity, and how their loss disrupts these processes, contributing to worsening of asthma.

overall_design: The microarray analysis was performed using lung tissue samples from 12 mice aged over 8 weeks, including both males and females, divided into four groups: three PDGFRα+ fibroblast-ablated mice and three control mice exposed to house dust mite (HDM), and three PDGFRα+ fibroblast-ablated mice and three control mice exposed to PBS. The Affymetrix Clariom S Assay mouse microarray platform (Thermo Fisher Scientific, 902930) was used to evaluate gene expression profiles.

first: Michelle

last: Tallquist

first: Ha

last: Shin

first: Sanyeowool

last: An

first: Jack

last: Heckl


title: Effects of Selenium-mediated RUNX2 Overexpression and its Transcriptome Alterations on Chondrocyte Injury in Kashin Beck disease

status: Public on Dec 04 2025

city: xi'an

first: Di

last: Zhang

state: shaanxi

address: No.76, Yanta West Road, Yanta District, Xi'an City, Shaanxi Province

institute: xi'an jiaotong university

summary: Runt-related transcription factor 2 (RUNX2) is a key regulator of chondrocyte differentiation and apoptosis. To investigate the downstream molecular mechanisms of RUNX2 in chondrocyte injury, we established a RUNX2 overexpression model using lentiviral transfection in human chondrocytes. Total RNA was extracted from RUNX2-overexpressing and control chondrocytes and subjected to RNA sequencing. Differential expression analysis identified 263 upregulated and 216 downregulated genes in RUNX2-overexpressing cells compared with controls. Functional enrichment analysis revealed that these genes were predominantly involved in TNF and MAPK signaling pathways, suggesting that RUNX2 activation promotes inflammatory and apoptotic processes in chondrocytes. These results provide a comprehensive transcriptomic resource for understanding RUNX2-mediated signaling in cartilage degeneration and may contribute to elucidating the molecular pathogenesis of osteoarthropathy such as Kashin-Beck disease.

overall_design: Human chondrocytes were transfected with a lentiviral vector encoding RUNX2 or an empty vector as control. Total RNA was isolated from each group (three biological replicates per condition) and subjected to high-throughput RNA sequencing for differential gene expression and pathway enrichment analysis.

first: Yongmin

last: Xiong

first: Shiquan

last: Sun


title: Histone H3K4 methylation regulation and three-dimensional aggregating distribution of a subset of genomic loci mediated by CHD3 homolog PKL in Arabidopsis [ChIP-Seq]

first: Mengfei

last: Song

address: 北京市海淀区颐和园路5号

first: Yuqiu

last: Wang

first: XingWang

last: Deng

first: Danmeng

last: Zhu


title: TBX21 facilitates the progression of prostate cancer by modulating the immunosuppression microenvironment via enhancing the proportion of Treg cells

city: Suzhou

first: Ouyang

last: Jun

address: No.899 Pinghai Road,Gusu District

institute: The First Affiliated Hospital of Soochow University

summary: Abstract Background: Prostate cancer (PCa) remains a major health burden, and identifying target molecules will provide new research ideas for treating PCa. TBX21 is a transcriptional factor with critical functions in tumor development, roles of which in PCa were studied herein. Methods: TBX21 expression was evaluated by RNA-seq, RT-PCR, Western blot, and immunohistochemistry in PCa tissues and cell lines. Functional assays were performed using LNCaP and 22RV1 cells with TBX21 knockdown to assess proliferation and apoptosis. Tumor growth and immune alterations were examined in xenograft and humanized immune cell models, while flow cytometry and Western blot were used to characterize immune cell subsets and effector molecules. Results: TBX21 expression was significantly elevated in PCa tissues and cell lines. TBX21 knockdown was associated with reduced proliferation and increased apoptosis in vitro and suppressed tumor growth in vivo. In humanized xenografts, TBX21 silencing was accompanied by a decrease in regulatory T cells (Treg) and an increase in Th17 and cytotoxic CD8⁺ T cells, together with enhanced expression of effector molecules (TNF-α, GZMB). Co-culture experiments showed that TBX21-deficient tumor cells reduced the induction of CD25⁺Foxp3⁺ Treg cells from activated CD4⁺ T cells. Conclusion: TBX21 is associated with tumor progression and an immunosuppressive microenvironment in PCa, underscoring its potential role in modulating the tumor–immune balance.

overall_design: Samples were sourced from the Department of urology, Lianyungang Affiliated Hospital of Nanjing University of Chinese Medicine, consisting of PCa tissues and corresponding paracancerous tissues from patients who underwent surgical treatment for PCa and were pathologically diagnosed with PCa. For RNA-seq analysis, three pairs of primary prostate cancer tissues and their matched paracancerous tissues were selected

first: Heng

first: Zhaofei

last: Liu

first: Xiangjun

last: Xu

first: Qichao

first: Pingan

last: Chang

first: Lei

last: He


title: Mechanistic Link Between Glyoxalase 1 Expression and Methylglyoxal-Induced Oncogenic Stress in Prostate Cancer

status: Public on Jan 31 2026

city: Duarte

first: Francisco

last: Nunez

state: CA

address: 1500 E Duarte Rd

institute: City of Hope

summary: Prostate cancer (PCa) is the second leading cause of cancer-related death in men, with African American/Black (AA/B) men experiencing significantly higher incidence and mortality than European American (EA) men. Obesity, which disproportionately affects AA/B men, is linked to increased PCa mortality, potentially through metabolic dysregulation. We hypothesize that methylglyoxal (MG), a reactive byproduct of glucose, lipid, and protein metabolism elevated in obesity, contributes to PCa progression. MG forms adducts on DNA, RNA, and proteins. Here, we found that MG-adducts are elevated in AA/B men with PCa compared to EA men and controls. AA/B men with PCa had a higher frequency of SNP rs1049346 in glyoxalase 1 (GLO1), the primary MG detoxification enzyme. PCa cell lines from EA (C4-2) and AA/B (MDA-PCa-2b) men showed differential SNP rs1049346 expression, with the former heterozygous and the latter homozygous for the SNP. This was associated with altered GLO1 expression and activity, with MDA-PCa-2b cells exhibiting reduced GLO1 function and increased MG-adducts compared to C4-2 cells. MG treatment altered DNA repair and RNA processing gene expression and induced distinct metabolic shifts in MDA-PCa-2b compared to C4-2 cells, including enhanced glycolysis and oxidative phosphorylation. Transcriptomic analysis revealed shared stress responses following MG treatment, but MDA-PCa-2b cells uniquely activated metallothionein and NOD1/2 immune signaling pathways in addition to TXNIP, a redox regulator linked to tumorigenicity in GLO1-deficient cancers. These findings suggest that MG stress may contribute to PCa progression in AA/B men through metabolic reprogramming and impaired detoxification, offering insight into racial disparities and potential therapeutic targets.

overall_design: RNA-seq profiling of C4-2 and MDA-Pca-2b prostate cancer cell lines treated with 7 mM glucose, 25 mM glucose or 500 µM methylglyoxal.

first: Alana

last: Battad

first: Mya

last: Walker

first: Sydney

last: Hodge

first: Keilani

first: Elise

last: Desjarlais

first: Edwin de Jesus

last: Lopez Gonzalez

first: Seigmund

last: Lai

first: Leanne

last: Wood-Burnham

first: Stanley

last: Hooker

first: Rayyan

last: Aburajab

first: Qianhua

last: Feng

first: Min

last: Talley

first: David

last: Craig

first: Rick

last: Kittles

first: Yun Rose

last: Li

first: John

last: Termini

first: Sarah

last: Shuck


title: A BRCT Domain-Containing Protein Induced in Early Phagocytosis Plays a Crucial Role in Mucorales Pathogenesis

city: Murcia

first: Carlos

last: Lax

address: Facultad de Biología

department: Genetics and Microbiology

country: Spain

institute: University of Murcia

type: Non-coding RNA profiling by high throughput sequencing

summary: Mucormycosis, caused by Mucoralean fungi, is among the most lethal fungal diseases, and a deeper understanding of its pathogenesis is urgently needed. In this study, we examined the early stages of fungal interaction with host macrophages using Mucor lusitanicus and Rhizopus microsporus as model organisms. Transcriptomic profiling of virulent (WT) and an RNAi-deficient strain (r3b2Δ) of M. lusitanicus strains during phagocytosis uncovered thousands of differentially expressed genes (DEGs), highlighting early metabolic activation as a key survival strategy inside the phagosome. Enriched pathways included amino acid transport, nucleotide metabolism, and translation, reflecting an adaptive fungal response to nutrient deprivation and host immune stress. Integrative analyses of mRNA and sRNA profiles also revealed a critical role of the RNAi pathways in modulating gene expression during infection. Building on these observations, we identified four chromatin- and transcription-related candidate virulence genes—brca1, box, hist1, and hda10—which were strongly upregulated during phagocytosis and regulated by RNAi. Functional validation through gene deletion in M. lusitanicus and disruption in R. microsporus revealed that while loss of these genes in M. lusitanicus did not significantly affect virulence, R. microsporus mutants for brca1, hist1, and hda10 showed attenuated virulence in a murine model. Our findings suggest that although M. lusitanicus remains a valuable tool for genetic manipulation, species-specific differences must be considered when studying virulence. The study also underscores the importance of using multiple Mucorales models to uncover conserved and divergent strategies employed by pathogenic fungi. These insights contribute to a broader understanding of fungal adaptation, immune evasion, and the identification of novel targets for antifungal intervention.

overall_design: Transcriptomic analysis using RNA-seq to study the impact of R3B2 gene deletion on gene expression at both messenger RNA (mRNA) and small RNA (sRNA) levels in Mucor lusitanicus. Wild-type strain MU636 and r3b2Δ mutant MU412 were used. Total RNA was extracted from samples collected after 1 hour of interaction with macrophages and after 1 hour of saprophytic growth as a control condition. Three biological replicates were performed for each condition.

first: Ghizlane

last: Tahiri

first: Ulrike

last: Binder

first: Jakob

last: Scheler

first: Eusebio

last: Navarro

first: Francisco E

last: Nicolás

first: Victoriano

last: Garre


title: ALS-Associated TDP-43 Dysfunction Compromises UPF1-Dependent mRNA Metabolism Pathways Including Alternative Polyadenylation and 3’UTR Length [RIP-Seq]

first: Evangelos

last: Kiskinis

state: IL

address: 303 E. Superior Street

institute: Northwestern University Feinberg School of Medicine

summary: UPF1-mediated decay entails several mRNA surveillance pathways that play a crucial role in cellular homeostasis. However, the precise role of UPF1 in postmitotic neurons remains unresolved, as does its activity in amyotrophic lateral sclerosis (ALS), a devastating neurodegenerative disease characterized by TDP-43 pathology and disrupted mRNA metabolism. Here, we used human iPSC-derived spinal motor neurons (MNs) to identify mRNAs subject to UPF1 degradation by integrating RNA-seq before and after UPF1 knockdown with RIP-seq to identify RNAs that co-immunoprecipitate with the active form of phosphorylated UPF1. We define a stringent set of bona fide UPF1 targets in MNs that are functionally enriched for autophagy and structurally enriched for GC-rich and long 3' UTRs but not for premature termination codon (PTC)-containing transcripts. TDP-43 depletion in iPSC-derived MNs reduces UPF1 phosphorylation and consequently post-transcriptional upregulation of UPF1 targets, suggesting that TDP-43 dysfunction compromises UPF1-mediated mRNA surveillance. Intriguingly, our datasets reveal that UPF1 and TDP-43 regulate alternative polyadenylation and 3'UTR length of mRNAs associated with synaptic and axonal function, a process that we find to be compromised in ALS models in vitro and ALS patient tissue. Our study provides a comprehensive description of UPF1-mediated mRNA decay activity in neurons, reveals overlapping roles between UPF1 and TDP-43 in regulating 3'UTR length, and offers novel insight into the intricate interplay between RNA metabolism and neurodegeneration in ALS.

overall_design: Sequencing of immunoprecipitated RNA from iPSC-derived spinal motor neurons. RNA was pulled down against either phosphorylated-UPF1 (pUPF1) or rIgG for non-specific binding. Input RNA was also sequenced and is included for background.

first: Francesco

last: Alessandrini

first: Matthew

last: Wright

first: Tatsuaki

last: Kurosaki

first: Lynne

last: Maquat


title: ALS-Associated TDP-43 Dysfunction Compromises UPF1-Dependent mRNA Metabolism Pathways Including Alternative Polyadenylation and 3’UTR Length

overall_design: RNA sequencing of iPSC-derived spinal motor neurons, treated with either a scrambled siRNA (control), or siRNAs to induce knockdown of TDP43, UPF1, or both


title: ALS-Associated TDP-43 Dysfunction Compromises UPF1-Dependent mRNA Metabolism Pathways Including Alternative Polyadenylation and 3’UTR Length [IPS_RNASeq]

overall_design: RNA sequencing of iPSCs, treated with either a scrambled siRNA (control), or an siRNA to induce knockdown of UPF1


title: Specific Intratumoral Microbiome Signatures in Human Glioblastoma and Meningioma: Evidence for a Gut–Brain Microbial Axis

city: Florence

first: Sara

last: Bertorello

address: Viale Gaetano Pieraccini 6

country: Italy

institute: University of Florence

summary: Brain tumors (BTs), including glioblastoma (GBM) and meningioma (MGM), contribute significantly to the global cancer burden. The microbiome has been implicated in carcinogenesis, yet its role in BTs remains underexplored. We performed 16S rRNA gene sequencing of the gut microbiota (GM) and intratumoral microbiome (ItM) from fresh tissue samples of 9 patients with GBM and 18 with MGM. 12 age- and sex-matched healthy controls (HCs) were also enrolled. GM profiling revealed reduced alpha diversity and distinct microbial communities in BT patients versus HCs. Notably, Verrucomicrobiota and Synergistaceae were enriched, while Lachnospiraceae, Peptostreptococcaceae, and Muribacter spp. were depleted. GBM patients showed reductions in Peptostreptococcaceae and the Eubacterium hallii group, while MGM patients had increased Synergistia and Erysipelatoclostridium. Compared with MGM, GBM patients were enriched in Peptostreptococcales–Tissierellales, Coprobacillus, and Peptoniphilus but depleted in Weissella. Venn analysis revealed 176 genera shared across groups with unique taxa distinguishing tumor patients and HCs. ItM profiling revealed enrichment of Proteobacteria, Actinomycetota, and Campylobacterota in GBM, while MGM contained higher levels of Bacillota and Bacteroidota. GBM tissues harbored Burkholderia-Caballeronia-Paraburkholderia, Helicobacter, and Leifsonia, whereas MGM tissues were dominated by Bacteroides and Blautia. Notably, stool and tumor samples shared 91 genera in GBM and 105 in MGM. This study provides novel insights by (i) characterizing ItM from fresh samples, (ii) comparing ItM profiles of GBM and MGM, (iii) linking GM and ItM within the same patients, and (iv) suggesting potential clinical implications for BT management.

overall_design: Brain tumors (BT), including glioblastoma (GBM) and meningioma (MGM), contribute significantly to the global cancer burden. While genetic, environmental, and lifestyle factors are well-recognized contributors to tumorigenesis, emerging evidence suggests a role for the microbiome, both gut and tumor-associated, in cancer development and progression. We performed 16S rRNA gene sequencing to characterize the gut microbiota (GM) and intratumoral microbiome (ItM) from fresh tissue samples in 9 patients with GBM and 18 with MGM. Additional 12 age- and sex-matched healthy controls (HC) were enrolled.

first: Dalila

last: Mehelleb

first: Abderezak

last: Ghidouche

first: Simone

last: Baldi

first: Ferhat

last: Djoudi

first: Leandro

last: Di Gloria

first: Matteo

last: Ramazzotti

first: Elena

last: Niccolai

first: Menad

last: Madaoui

first: Idir

last: Takbou

first: Souhil

last: Tliba

first: Amedeo

last: Amedei


title: Characteristics of immunity system in postoperative delirium patients by single-cell transcriptomic analysis

city: Chengdu

first: Juan

last: Wu

state: Sichuan

address: No. 37 Guo Xue Alley, Wuhou District

department: Anesthesiology

institute: West China Hospital of Sichuan University

summary: Background: Postoperative delirium (POD) is the most complication after cardiac surgery, and associated with increased mortality and decreased long term cognition ability. Our study aimed to explore the characteristics of immunity system in POD patients. Methods: This prospective study included patients scheduled for selective on-pump cardiac surgeries, who were divided into Non-POD and POD group according to whether POD occurred within 30 days after surgery. Multi-channel spectral flow cytometry, single-cell sequencing and plasma cytokines measurement were performed to describe the characteristics of immunity system in POD patients before surgery and at 24 hours after surgery. Results: A total of 120 patients were included, and 12 were diagnosed as POD within 30 days after surgery. T cells and B cells were activated in POD patients before and after surgery, and the upregulation of related genes contributed to the activation of chemotaxis in GZMK+ CD8+ T cells and memory B cells, which was confirmed by the elevation of CCL3 and CXCL8 concentration in plasma and the increased expression of chemotaxis related ligands-receptors pairs (CCL16_CCR1 and CXCL13_CXCR5). The inflammation response was enhanced in CD4+ T cells, which was confirmed by the activation of many cytokines related pathways and increased plasma level of IL-17 and IL-4 in POD patients before and after surgery. In monocytes, antigen presentation process and complement response were enhanced in POD patients before and after surgery, which was confirmed by the increased relative abundance of antigen presentation related surface markers (CD80, HLA-DR), activation of gene sets related to antigen binding and complement activation, and increased expression of related ligands-receptors pair (HLA-A_KIR3DL1 and C3_C3AR1).

overall_design: We performed single-cell RNA sequencing of peripheral blood mononuclear cells from patients with or without POD at Pre-surgery and at 24 hours after surgery. The sequencing profiles were used to cluster the cells into the following four immune cell types based on expression of well-established markers: monocytes, T cells, B cells, and natural killer cells.


title: scRNA-seq of primary mouse and human cerebellar nestin-expressing progenitor neurosphere cultures

city: Cambridge

first: Jens

middle: Bager

last: Christensen

address: Tennis Court Road

department: Gurdon Institute

country: United Kingdom

institute: University of Cambridge

summary: Nestin-expressing progenitors (NEPs) of the developing cerebellum give rise to Bergmann glia, astrocytes and molecular layer interneurons via molecularly distinct subtypes. NEPs can be cultured in vitro as neurosphere in presence of growth factors. In order to characterise the primary neurosphere cultures generated from mouse and human developing cerebella, we performed single cell RNA-sequencing of primary NEP cultures established from 9-17 post-conception week human fetal cerebella and postnatal day 1 old mouse cerebella from two different mouse strains.

overall_design: Primary NEP cultures were established from mouse and human cerebellar tissues and expanded in vitro in media containing 20 ng/mL EGF and FGF2. 12 different primary lines (2 mouse, 10 human) were dissociated into single cells and single cell RNA-sequencing was performed using CellPlex Multiplexed, 10X NextGEM 3' v3.1 chemistry.

middle: B

first: Giada

last: Vanacore

first: N. Sumru

last: Bayin


title: Targeting Polycomb for treatment of KMT2A-rearranged AML using AML-iPSCs as a model system

city: Huddinge

first: Anna

last: Palau

address: Hälsovägen 9

institute: Karolinska Institutet

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

overall_design: Refer to individual Series


title: MYEOV is a novel marker of differentiated corneal epithelium

city: Seattle

first: Yuzuru

last: Sasamoto

state: WA

address: 750 Republican St

department: Ophthalmology

institute: University of Washington

summary: PURPOSE. Myeloma Overexpressed gene (MYEOV) was initially identified as a gene amplified in several malignancies, and it was found to promote cell proliferation and metastasis. Our previous comparative RNA-seq and epigenetic analyses revealed high MYEOV levels in differentiated corneal epithelial cells and showed that MYEOV expression was epigenetically regulated by TET2. In the current study, we aimed to characterize further the expression and regulation of MYEOV in the human ocular surface epithelium.  METHODS. MYEOV expression was examined by immunostaining and publicly available single-cell RNA-seq data. Gene knockdown (KD) of MYEOV and the regulators of corneal epithelial differentiation, PAX6 and KLF4, in in vitro-expanded corneal epithelial cells was performed by siRNA transfection. Protein expression levels were examined by Western blot. MYEOV KD cells were subjected to colony-forming assay and RNA-seq analysis.  RESULTS. Human cornea immunostaining revealed high MYEOV expression in the nuclei of KRT12-positive differentiated corneal epithelial cells, while KRT13-positive differentiated conjunctival epithelial cells were MYEOV-negative. MYEOV expression was not detected in the other surface ectoderm-derived epithelia: epidermis and oral mucosa. Both PAX6 KD and KLF4 KD led to the reduction of MYEOV and KRT12 protein expression. MYEOV KD decreased colony-forming efficiency while afflicting limited global gene expression change.  CONCLUSIONS. Our study revealed specific MYEOV expression in KRT12-positive corneal epithelial cells among surface ectoderm-derived epithelia. Similar to KRT12, MYEOV expression is regulated by PAX6 and KLF4. Functionally, MYEOV regulates cell proliferation of corneal epithelial cells.

overall_design:
Comparative gene expression profiling analysis of RNA-seq data. We used cultured human corneal epithelial cells treated with siRNAs (Control, MYEOV knockdown #1, and MYEOV knockdown #2)

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

last: Fukuda

first: Chao

last: Zhang

first: Bruce

last: Ksander

first: Vickie

last: Jo

first: Christine

last: Lian

first: George

last: Murphy

first: Markus

last: Frank

first: Natasha


title: Sensitive and unbiased genome-wide profiling of base-editor-induced off-target activity with CHANGE-seq-BE [Digenome-seq]

status: Public on Dec 03 2025

city: Memphis

first: Shengdar

last: Tsai

state: TN

address: 262 Danny Thomas Pl

department: Department of Hematology

institute: St Jude Children's Research Hospital

summary: To compare the sensitivity of CHANGE-seq-BE to another leading off-target discovery method, we performed Digenome-seq on the same ABE and CBE targets and evaluated them with matching analysis parameters. Many low-frequency off-target sites with editing rates were not identified by Digenome-seq and were only discovered by CHANGE-seq-BE.

overall_design: Digenome-seq applied for ABEs and CBEs targeting B2M, CBLB, CD7, CIITA, and PDCD1 in primary human T-cells

first: Rachael

middle: K

last: Wood

first: Varun

last: Katta

first: Jacqueline

last: Chyr

first: Yichao

last: Li


title: Impact of desiccation on the global transcription of Acinetobacter baumannii AB5075

city: Southampton

first: Rubén

last: de Dios

state: Hampshire

address: University Road

department: School of Biological Sciences

institute: University of Southampton

summary:
We perform RNA-seq comparing A. baumannii AB5075 cells resuspended in water or diluted M9-succinate and desiccated during 24 h (relative humidity 8-12%) to cells resuspended in water before desiccation.
A. baumannii AB5075 cultures (3 independent biological replicates) were grown overnight (approx. 16 h) in M9 minimal medium supplemented with Na-succinate 20 mM. Cultures were split in two and each half was washed 3 times either with distilled water or with M9-succinate 20 mM diluted 1:250 (v:v). OD600 of the cell supensions was adjusted to 1.0 and 1 ml from the water-suspended cells was withdrawn as a control comparison, washed with RNAlater and stored at -80 C until further processing. 1 ml of the OD-adjusted water- and M9-suspended cells were spotted on polystyrene Petri dishes and left to air-dry in a laminar flow hood. Once dried, the plates were placed in a chamber with Drierite until reaching a relative humidity of 8-12% and were incubated during 24 h. Finally, cells were harvested by directly resspending them in RNAlater and stored at -80 C. After that, total RNA was extracted from each sample and cDNA libraries were generated and sequenced.
The different comparisons showed that: i) 309 and 279 genes were upregulated and downregulated, respectively, in cells ressupended in water and desiccated compared to the control; ii) 435 and 512 genes were upregulated and downregulated, respectively, in cells resuspended in diluted M9-succinate and desiccated compared to the control; iii) 327 and 242 genes were upregulated and downregulated, respectively, in the cells resupended in water and desiccated compared to the cells resuspended in diluted M9-succinate and desiccated.

overall_design: Three independent replicates of A. baumannii AB5075 were grown overnight in M9 minimal medium supplemented with Na-succinate 20 mM, split in two equal volumes, washed 3 times with either distilled water or M9-succinate diluted 1:250 (v:v) and the OD600 was adjusted to 1.0. Then, 1 ml of each sample was spotted on a Petri dish and was left to air-dry. When dry, the Petri dishes were placed in a chanber with 8-12% relative humidity and were icubated for 24 h. 1 ml of the water suspended cells were withdrawn as control condition.

first: Lyuboslava

middle: G

last: Harkova

first: Ronan

middle: R

last: McCarthy


title: Uracil-DNA glycosylase deficiency is associated with repressed tumor cell-intrinsic inflammatory signaling and altered sensitivity to exogenous interferons

city: Pittsburgh

first: Christopher

last: Bakkenist

address: 5051 Centre Avenue

department: Radiation oncology

institute: university of pittsburgh

summary: 2’-deoxyuridine (dU) is a common DNA lesion resulting from cytosine deamination and from dUMP incorporation by DNA polymerases, both of which are prevalent in cancer. The primary mechanism that repairs dU lesions in genomic DNA is base excision repair initiated by Uracil-DNA Glycosylase 1 (UNG1). We generated Ung knockout mouse B16 melanoma cells to investigate the consequences of UNG deficiency in a well-characterized, immunoproficient, syngeneic mouse cancer model. We show that UNG-deficient (ΔUNG) B16 tumors have altered growth kinetics in vivo and that their delayed growth is T-cell dependent. Immune profiling revealed reduced CD8+ T cell infiltration but augmented CD4+ Th1 responses in ΔUNG tumors. In vitro, ΔUNG tumor cells exhibit strongly suppressed cell-intrinsic type-I interferon, type-II interferon, and inflammatory signaling gene expression signatures as well as altered cytokine and chemokine secretion. In vivo, ΔUNG tumors exhibit a modified inflammatory cytokine and chemokine milieu. Furthermore, ΔUNG tumor cells have altered sensitivity to exogenous interferons in vitro, with increased sensitivity to IFN-γ but decreased sensitivity to IFN-α/β. Collectively, our data show that tumor cell-specific UNG deficiency results in an altered tumor microenvironment in vivo and provide proof-of-concept data for the use of UNG inhibitors to modulate inflammatory pathways in tumors.

overall_design: B16F10 wildtype (cas9 control) and UNG knockout clones (ΔUNG and ΔUNG_2) cells treated with DMSO or 5uM ATRi (AZD6738) for 48h.  Study was performed using two biological replicate per each condition and each cell line

first: Frank

middle: P

last: Vendetti

first: Pinakin

last: Pandya

first: Carina

last: Sclafani

first: Sudipta

last: Pathak

first: Raquel

last: Buj

first: Reyna

last: Jones

first: Daniel

last: Ivanov

first: Katherine

middle: M

last: Aird

first: Robert

last: Sobol


title: Maternal Western-Style Diet alters Kupffer Cell proportion leading to Metabolic Dysfunction-Associated Steatotic Liver Disease when challenged with western diet in adulthood

city: OKC

first: Sarah

middle: Jane

last: Miller

state: OK

address: 940 Stanton L. Young Blvd

institute: University of Oklahoma Health Sciences Center

summary: Exposure to maternal western-style diet (mWD) is associated with early development of metabolic dysfunction-associated fatty liver disease (MAFLD) in offspring. Kupffer cells (KCs), the main resident macrophage population in the liver, are known to promote MAFLD progression, however, the effects of mWD on KC subtypes, ontogeny, and gene expression in offspring are not fully understood. In this manuscript, we used two different models of mWD exposure and challenge in adulthood to understand the impact of mWD on KC proportion, ontogeny, and gene expression in adult offspring. Our data indicate that in the absence of challenge in adulthood, mWD results in increased KC proportion in offspring, with limited changes in KC ontogeny or liver phenotype. In contrast, mWD mice challenged with WD in adulthood had increased expression of inflammatory (Nlrp3) and fibrosis (Tgfb1) related genes compared to chow (CH)-WD fed mice. Although KC proportion and ontogeny were similar when comparing CH-WD and WD-WD fed mice, we found that WD-WD mice had a greater reduction in KC proportion and TdT labelling than CH-WD fed mice when normalized to their respective maternal diet controls. Similar results were found when mice were weaned onto normal chow and re-challenged with WD later on in adulthood. Bulk RNA sequencing data indicate that KCs from mWD mice re-challenged with WD in adulthood had increased expression of inflammatory and antigen presenting genes compared to KCs isolated from WD fed mice lacking mWD exposure. These findings highlight the intergenerational repercussions of mWD on liver phenotype as well as KC proportion and ontogeny and provide novel insight into the mechanisms dictating MAFLD.

overall_design: Bulk RNA seq profiling of the offspring from WD of CH fed dams, with and without WD challenge in adulthood.

first: Rachel

middle: C

last: Janssen

first: Wanke

last: Zhao

first: Karen

last: Jonscher

first: Hua

last: Zhong

first: Christa

last: DeVette

first: Jacob

last: Friedman

first: Kurt

middle: A

last: Zimmerman