title: Single Cell Transcriptome Signatures of Sarcoidosis in Lung Immune Cell Populations

city: Denver

first: Camille

last: Moore

address: 1400 Jackson St.

institute: National Jewish Health

summary: Rationale: To identify cell specific molecular changes associated with sarcoidosis risk and progression, we aimed to characterize the cellular composition, gene expression patterns, and cell-cell interactions in BAL cells from patients with sarcoidosis (both progressive and non-progressive) and healthy controls. Methods: Single cell RNA-seq data were collected on 12 sarcoidosis and 4 control participants. We combined scRNA-seq data from these participants with our previously collected data on 4 sarcoidosis and 10 control participants for a final sample size of 16 sarcoidosis cases (8 progressive and 8 non-progressive) and 14 controls. Following initial preprocessing in Cell Ranger, data were quality controlled, combined, and clustered in Seurat. We tested differences in cell proportions by disease group using F-tests on cell proportions and differences in gene expression using pseudobulk analysis. Cell to cell communication and pathway analysis were performed using CellChat. Results: We identified five macrophage populations: resident, high metallothionein (MT) resident, recruited, profibrotic recruited, and proliferating macrophages. Each subpopulation displayed unique gene expression profiles, with notable differential expression of genes and pathways linked to sarcoidosis in resident macrophages, recruited macrophages, and proliferating macrophages. We also observed changes in gene expression associated with disease progression in resident and recruited macrophages. In non-macrophages cells, we observed a significant reduction in the number of B cells in sarcoidosis patients compared to controls. Among T cell populations, we identified specific transcriptional alterations at gene and pathway level. Additionally, we observed distinct differences in cell-to-cell interactions of macrophages and T cells between sarcoidosis patients and healthy controls. Conclusions: These findings underscore the complexity of immune cell involvement in sarcoidosis and highlight potential cellular and molecular targets for further investigation.

overall_design: All sarcoidosis subjects met the ATS/ERS criteria (DOI: 10.1164/rccm.202002-0251ST) for tissue biopsy confirmation of diagnosis of sarcoidosis. The non-progressive phenotype was defined as having either acute (i.e. consistent with Lofgren’s syndrome) or non-acute disease presentation, no new organ involvement, lung function testing with <10% decline in FVC or FEV1, <15% decline in DLCO, and stable chest imaging within 2 years after BAL. The progressive phenotype had a non-acute disease presentation; lung function testing with ≥10% decline in FVC or FEV1; or ≥15% decline in DLCO; worsening chest imaging; and/or if they required initiation of systemic immunosuppressive treatment any time up to 2 years after BAL.

first: Shu-Yi

last: Liao

first: Cheyret

last: Wood

first: Arunangshu

last: Sarkar

first: Jonathan

last: Cardwell

first: Kristyn

last: MacPhail

first: Margaret

middle: M

last: Mroz

first: Christina

last: Riley

first: Kara

last: Mould

last: Restrepo

first: Li

last: Li

first: Lisa

last: Maier

first: Ivana

middle: V

last: Yang


title: Effects of ACTH and Dexamethasone on the Transcriptomic Profile of the Rat Adrenal Gland: An In Vivo Study

status: Public on Jan 29 2026

city: Poznan

first: Marcin

last: Rucinski

address: Swiecicki 6

department: Histology and Embriology

country: Poland

institute: Poznan University of Medical Science

summary:
The hypothalamic-pituitary-adrenal (HPA) axis plays a pivotal role in regulating stress responses through ACTH-stimulated glucocorticoid production. Adult male Wistar rats were subjected to acute ACTH stimulation (single injection, 1 h), prolonged ACTH exposure (three injections over 36 h), or Dexamethasone treatment (three injections over 36 h). Plasma corticosterone levels were measured using ELISA. Adrenal transcriptome profiling was performed using Affymetrix Rat Gene 1.1 ST Arrays. Differentially expressed genes (DEGs; |fold change| >= 1.8, adjusted p < 0.05) were analyzed using limma, followed by pathway and network analyses.
Acute ACTH exposure resulted in induction of 569 DEGs (357 upregulated), including immediate-early genes (Nr4a family, AP-1 factors), cAMP-PKA-CREB signalling components, and heat shock proteins. Prolonged ACTH resulted in 98 DEGs (predominantly downregulated), including suppression of mitochondrial genes and upregulation of Polycomb repressive complex 2 components. Dexamethasone treatment yielded 75 DEGs with selective suppression of SREBP-mediated cholesterol biosynthesis and uptake pathways.

overall_design:
Adult male Wistar rats (160-200 g) were randomly assigned to four experimental groups (n=3 per group, 12 animals total). Control group (C) received saline injections at 0, 12, and 24 h and were decapitated 12 h after the last injection. Acute ACTH group (ACTH_A) received a single ACTH injection (Synacthen, 5 μg/rat) and were decapitated 1 h post-injection. Prolonged ACTH group (ACTH_P) received ACTH injections at 0, 12, and 24 h and were decapitated 12 h after the last injection. Dexamethasone group (DEX) received Dexamethasone injections (5 μg/rat) at 0, 12, and 24 h and were decapitated 12 h after the last injection. Total RNA was extracted from adrenal glands and analyzed using Affymetrix Rat Gene 1.1 ST Arrays.
Grant ID: 2020/38/E/NZ4/00020
Grant title: The role of MOTS-c peptide in the regulation of adrenal cortex physiological function
Funding source: National Science Centre, Poland (NCN)
Grantee: Marcin Rucinski

first: Emilia

last: Cicha

first: Małgorzata

last: Blatkiewicz

first: Karol

last: Jopek

first: Marta

last: Szyszka

first: Piotr

middle: W

last: Malendowicz

first: Anna

last: Olechnowicz

first: Ludwik

middle: K


title: Gαi1 and Gαi3 Mediate IL-11-Induced Signal Transduction and are Potential Therapeutic Targets for LUAD

status: Public on Jan 27 2026

city: suzhou

first: Gaomeng

last: Luo

address: 199 Renai Road, Industrial Park

country: China

institute: soochow university

type: Expression profiling by high throughput sequencing

summary: Lung adenocarcinoma (LUAD) is the main histologic subtype of lung cancer, and its incidence is on the rise. However, since the vast majority of patients are already in advanced stages at the time of diagnosis, their 5-year survival rate is only 15%, so it is urgent to explore the mechanism of the development of LUAD and improve the survival time of patients. Interleukin-11 (IL-11), a member of the IL-6 cytokine family, has an influential role in the development and progression of a variety of tumors, but the specific molecular mechanisms that promote the malignant progression of LUAD are unknown. Here, we found that the IL-11-induced activation of Akt, Erk, and STAT3 could be inhibited by knocking out the expression of Gαi1/3. In contrast, overexpression of Gαi1/3 could enhance IL-11-induced signaling. The binding of Gαi1/3 to GP130 mediates IL-11-induced downstream activation of Akt-mTOR, Erk, and STAT3, which requires recruitment of Grb2-associated binding protein 1 (Gab1). In LUAD cells, shGαi1/3 inhibited cell growth, proliferation, and migration as well as blocked the tumor-promoting ability of IL-11. However, overexpression of Gαi1/3 enhanced the IL-11-induced cell growth, proliferation, and migration. ShGαi1/3 also inhibited the proliferation of LUAD cells in vivo. Overall, the findings of this study demonstrate the Gαi1 and Gαi3 are critical for IL-11 signal transduction. Moreover, we reveal that Gαi1 and Gαi3 are highly expressed and associated with poor overall survival in lung adenocarcinoma and may thus act as potential therapeutic targets in LUAD. These results provide a novel therapeutic strategy for LUAD patients with upregulated IL-11 expression.

overall_design: To investigate the role of IL11 in lung adenocarcinoma, we constructed A549 cell lines transfected with lentiviruses expressing scr-shRNA and sh-IL11, respectively.

first: Wenxuan

last: Hu

first: Jian

first: Zheng

last: Lu

first: Yuan

last: Cui

first: Weibiao

last: Zeng

first: Hao

last: Ding

first: Qifan

first: Zhike

last: Chen

first: Xin

last: Tong

first: Cheng

first: Chun

last: Xu

first: Jun

last: Zhao


title: Effect of intrauterine growth restriction on the H3K4me3, H3K9ac, H3K27ac and H3k9me3 histione modification of microglia in hippocampus

status: Public on Jan 30 2026

city: Shanghai

first: Zhu

last: wei

address: siping road 1239

institute: tongji university

type: Genome binding/occupancy profiling by high throughput sequencing

summary: Early-life exposures (spanning from the gamete stage to childhood) to adverse environmental factors can exert long-term effects on offspring health through epigenetic modifications, significantly increasing susceptibility to chronic diseases such as neuropsychiatric disorders in adulthood. Previous studies have shown that fetal growth restriction can lead to excessive activation of microglia in the individual's brain, but there is still a lack of research on its epigenetic mechanisms. Our data supplements the gap of  changes of H3K4me3, H3K9ac, H3K27ac and H3K9me3 histone modification  of microglia in the hippocampus of individuals with fetal growth restriction, and explores the epigenetic basis of microglial activation

overall_design: ULI-NChIP-seq profiling of hippocampus microglia in control and FGR mice at postpartum three week


title: AMPK mutant dauer transcriptome [RNA-seq daf2_aak_alg34]

city: Montreal

first: Sabih

last: Rashid

state: Quebec

address: 3611 Rue Sainte Famille, Unit 11

department: Biology

country: Canada

institute: McGill University

summary: C. elegans lacking AMPK do not exhibit reproductive defects during normal growth, but when passaged through dauer, exhibit germline hyperplasia and premature spermatogenesis, followed by complete sterility post-dauer (Narbonne and Roy, Development, 2006). Loss of RNAi pathway  components suppresses several of these phenotypes (Kadekar and Roy, PLoS Biol, 2019). We sought to carry out a transcriptomic analysis of control and AMPK mutant animals in the dauer and post-dauer stage to understand what gene expression changes occur due to the absence of AMPK, and how RNAi pathway components may be affected. The daf-2 mutation was used to induce dauer by a temperature shift to 25 °C.

overall_design: RNA-Seq of dauer (96 hours post-hatching at restricted temperature) and post-dauer (96 hours after shift to permissive temperature) in the daf-2 and daf-2; aak-1; aak-2 (aak(0)), and daf-2; aak(0); alg-3; alg-4 (alg-3/4) genetic backgrounds. Standard Trizol RNA extraction of collected samples.

first: Rashid

last: Sabih

first: Roy

last: Richard


title: The effect of lncRNA GAS5 on lens epithelial cells

status: Public on Jan 26 2026

city: zhengzhou

first: Deqian

last: Kong

state: henan

address: No.1 Longhu Zhonghuan Road, Jinshui District

institute: The First Affiliated Hospital of Zhengzhou University

summary: Through transcriptome sequencing screening, it was found that knocking down GAS5 significantly disrupted the mRNA expression of key factors related to aging secretion phenotype, cell cycle inhibitory proteins, and antioxidant enzymes.

overall_design: This suggests that GAS5 may maintain the homeostasis of lens epithelial cells and delay aging by regulating the aging related gene network.


title: Inflammatory epiCaspase-1 dampens immunogenic cell death by remotely skewing bone marrow hematopoiesis to drive systemic neutrophil-dominant inflammation [T24 RNAseq]

status: Public on Feb 06 2026

city: Houston

first: Stephen

middle: Qi Rong

last: Wong

state: Texas

address: 6670 Bertner Ave

country: USA

institute: Houston Methodist

summary: While local immunological effects of chemotherapy-induced tumor cell death are well studied, its systemic impact on distant bone marrow—a site essential for immune cell maturation—remains underexplored. Here, we show that gemcitabine chemotherapy induces inflammatory caspase-1 activation in epithelial cancer cells (epiCaspase-1), triggering pyroptotic cell death. Despite its inflammatory nature, epiCaspase-1 mediated cell death is non-immunogenic. Clinically, cancer patients with high expression of a newly derived epiCaspase-1 gene signature show poorer outcomes. Mechanistically, epiCaspase-1 induces noncanonical release of IL-1α through NINJ1 lytic pores, which remotely skews bone marrow hematopoiesis towards granulocyte-monocyte progenitors and mature neutrophil output. This systemic alteration leads to a heightened neutrophil-to-lymphocyte ratio (NLR) in both peripheral blood and the tumor microenvironment. Notably, pharmaceutic inhibition of caspase-1 blocks this cascade, normalizes hematopoiesis, and recalibrates NLR to favor intratumoral CD8+ T cell infiltration and activation—ultimately improving chemotherapeutic efficacy. These findings underscore that inflammatory pyroptosis is not inherently immunogenic, instead, it reshapes systemic immune landscape towards neutrophil-dominant inflammation in the chemotherapy context.

overall_design: T24 human bladder cancer cell lines were treated with LPS and Nigericin, and then subjected to RNA sequencing.

middle: Q

first: Ethan

middle: J

last: Subel

first: Yung Hsing

last: Huang

first: Keith

middle: S

last: Chan


title: Multiscale analysis and functional validation of the cellular and genetic determinants of skeletal disease

city: SYDNEY

first: Peter

last: Croucher

state: NSW

address: 384 VICTORIA ST, DARLINGHURST NSW 2010

country: Australia

institute: Garvan Institute of Medical Research

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: Protein kinase CK2α’ as a Dual Modulator of Immune Signaling and Synaptic Dysfunction in Tauopathy

city: Minneapolis

first: Ying

last: Zhang

state: MN

address: 117 Pleasant St S.E.

department: Minnesota Supercomputing Institute

institute: University of Minnesota

summary: Protein kinase CK2α’ is upregulated in patients with tau-associated dementias and in the PS19 mouse model of tauopathy. CK2α’ haploinsufficiency in the PS19 mouse model improved tau pathology, synaptic density, synaptic function, cognitive behavior and disease-associated microglia phenotypes. We hypothesized CK2α’  haploinsufficiency would impact dysregulated gene expression in the PS19 model.  We found that CK2α’  haploinsufficiency led to enhanced synaptic gene network expression and enhance immune gene network expression.

overall_design: RNA-Seq analysis of samples obtained from the hippocampus of ~7 month-old mice using: 4 Wildtype, 5 CK2α’(+/-), 3 high-pathology PS19, 4 low-pathology PS19 and 4 PS19;CK2α’(+/-) mice. Mice are on a mixed C57Bl/6 x B6C3H background. Animals were anesthetized with Avertin and intracardially perfused with Heparin in Tris-buffered Saline. Brains were dissected and hippocampus samples were flash frozen in liquid nitrogen prior to RNA extraction.

first: Angel

last: White

first: Rocio

last: Gomez-Pastor


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

city: Xiamen

first: dang

last: buyun

state: Fujian

address: Xiang 'an District Xiang Annan Road

institute: xiamen university

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

overall_design: The BMDM macrophages of WT or Smyd5 KO were treated with IL-4 for 24 hours and then ATAC library construction was performed

first: Buyun

last: Dang

first: Yuling

last: Hong

first: Qingxiang

last: Gao

first: Shih-Chin

last: Cheng


title: Self-clustering of three CBX2 molecules drives PRC2 to promote facultative heterochromatinization of Polycomb target genes [Cut & Run, Cut & Tag]

status: Public on Feb 05 2026

city: Aurora

first: Srinivas

last: Ramachandran

state: CO

department: Biochemistry and Molecular Genetics

institute: University of Colorado School of Medicine

summary: Phase separation is increasingly recognized in facultative heterochromatinization of Polycomb target genes; however, the underlying mechanisms remain obscure. Using single-molecule imaging and tracking, we show that individual condensates in mESCs contain approximately 3 CBX2 molecules and numerous PRC1 and PRC2 subunits and indicate that the composition and dynamics of condensates are developmentally regulated. We reveal that CBX2 clusters PRC2 and controls the spatial distribution of both PRC2 and H3K27me3. Using genomic approaches, we demonstrate that CBX2 binds condensate initiation sites enriched for PRC2 nucleation sites. CBX2 deletion causes PRC2 and H3K27me3 to redistribute from their regular targets. By developing a separate-of-function variant, we determine that CBX2 relies on its self-clustering ability to function. These findings collectively support a novel phase-separation model driven by nucleation and bridging, in which low-abundance proteins self-cluster to initiate condensate assembly, a process tightly coupled to function.

overall_design: CUT&RUN of tagged CBX2 and EZH2 in CBX2fl/fl-HaloTag EZH2-Venus-dTag, CUT&RUN of tagged CBX2-PSM-HT  in CBX2fl/fl-HaloTag & Parental Cells,  CUT&Tag of H3K27me3 in mESCs (CBX2 WT, CBX2 KO, CBX2 PSM, and PGK12.1) in two biological replicates.

first: Steven

last: Ingersoll

first: Abby

last: Trouth

first: J. Carlos

last: Angel

first: Xinlong

last: Luo

first: Axel

last: Espinoza

first: Joey

last: Wen

first: Chengjie

last: Zhu

first: Joseph

last: Tucker

first: Kalkidan

last: Astatike

first: Christopher

last: Phiel

first: Hatim

last: Sabaawy

first: Tatiana

middle: G

last: Kutateladze

first: Tao

last: P. Wu

first: Tingting

last: Yao

first: Chao

last: Lu

first: Xiaojun

last: Ren


title: Self-clustering of three CBX2 molecules drives PRC2 to promote facultative heterochromatinization of Polycomb target genes [Hi-C]

first: Srinivas

last: Ramachandran


title: Multiomic analysis reveals that polyamines alter G. vaginalis-induced cervicovaginal epithelial cell dysfunction

city: Hanover

first: Olha

last: Kholod

state: NH

address: 15 Thayer Drive

institute: Dartmouth College

summary: An anaerobe-dominant, Lactobacillus-deplete cervicovaginal microbiome is associated with adverse reproductive outcomes. Gardnerella vaginalis, a common cervicovaginal anaerobe, alters cervicovaginal epithelial cell function, resulting in inflammatory immune responses and epithelial barrier breakdown. Specific host-microbial mechanisms inducing this epithelial dysfunction remain unknown. Here we show microbe-specific alterations in cervicovaginal epithelial cell metabolite profiles where G. vaginalis, but not Lactobacillus crispatus, increases polyamine biosynthesis. Pretreatment with polyamines (putrescine, spermidine and spermine) globally shifts G. vaginalis-induced transcriptomic profiles. Alterations in transcripts encoding enzymes responsible for polyamine synthesis and catabolism provides further evidence that G. vaginalis modifies polyamine biosynthesis. Additionally, polyamine-mediated transcriptomic changes include genes related to bacterial defense, inflammation, and epigenetic processes. Polyamines mitigate G. vaginalis-induced inflammatory responses through reduction of cytokines, chemokines, and matrix metalloproteinases. The ability of cervicovaginal metabolites to alter microbe-mediated changes in epithelial cell function suggests that metabolite-microbe interactions are critical mediators of epithelial defense against a Lactobacillus-deplete microbiota.

overall_design: Human cervicovaginal epithelial cell lines (Ectocervical, Endocervical, and Vaginal) were exposed to Gardnerella vaginalis (10⁷ CFU/well) for 24 hours to characterize microbe-induced transcriptional responses. To assess the impact of vaginal polyamines on these responses, cells were pretreated for 4 hours with putrescine (4 mM), spermidine (400 µM), or spermine (400 µM) prior to G. vaginalis exposure. Control conditions included untreated cells and G. vaginalis exposure without polyamines. Total RNA was extracted, ribosomal RNA–depleted, and sequenced using the CORALL total RNA-seq protocol on an Illumina NovaSeq platform.

first: Lauren

last: Anton

first: Rutuja

last: Phatate

first: Briana

last: Ferguson

first: Kristin

last: Klohonatz

first: Brittany

middle: A

last: Goods

middle: D

last: Gerson


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

city: Nanjing

first: Zhiqiang

last: Huang

state: Jiangsu

address: Hankou 22

department: Medical School

institute: Nanjing University

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

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

first: Panpan

last: Lian

first: Hongwei

last: Wang


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

city: Boston

first: Adam

middle: C

last: Gower

state: MA

address: 72 East Concord Street, E632

department: Department of Medicine

institute: Boston University School of Medicine

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

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

first: Dylan

last: Steiner

first: Marc

middle: E

last: Lenburg


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

city: Melbourne

first: Dale

last: Garsed

state: Victoria

address: 305 Grattan St

department: Cancer Research

institute: Peter MacCallum Cancer Centre

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

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

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

first: Tibor

last: Zwimpfer

first: Ahwan

last: Pandey

first: David

last: Bowtell


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

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


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


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

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

***************************************************************
Submitter states that missing raw data are being made available for controlled access in dbGaP.
***************************************************************


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

status: Public on Jan 25 2026

city: Kurashiki

first: Yoji

last: Kawano

state: Okayama

department: Institute of Plant Science and Resources

country: Japan

institute: Okayama University

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

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


title: β-Elemene Enhances the Efficacy of PD-L1 Inhibitor in Lung Cancer by Reprogramming Tumor-Associated Macrophages to M1 Phenotype via Suppressing FLT1/PI3K/AKT Signaling

status: Public on Jan 24 2026

city: Chongqing

first: Jianmin

address: No.6, Panxi Seventh Branch Road, Jiangbei District

institute: Chongqing Traditional Chinese Medicine Hospital

summary: Immune checkpoint inhibitors (ICI), epitomized by PD-1/PD-L1 antibodies, have ushered in a new era in lung cancer treatment. However, ICI monotherapy is only applicable to a small subset of patients with high PD-L1 expression, while most patients with low expression require combination therapies. In this study, we found that β-elemene promotes M1 polarization of tumor-associated macrophages (TAM) and enhances the efficacy of PD-L1 antibody (aPD-L1) in C57BL/6 mice. RNA sequencing and surface plasmon resonance revealed that β-elemene directly binds to FLT1 and inhibits the PI3K/AKT/FOXO1 signaling pathway, thereby mediating TAM M1 polarization. Using FLT1 knockout mice, we further validated the critical role of FLT1 in TAM polarization and confirmed that M1 polarization synergizes with aPD-L1 treatment. Furthermore, co-immunoprecipitation demonstrated that the intracellular domain of FLT1 interacts with and phosphorylates the p85α subunit, initiating downstream signaling cascades. These findings elucidate the synergistic mechanism between β-elemene and aPD-L1. Importantly, as both agents are already clinically approved, we plan to conduct a clinical trial to evaluate the efficacy and safety of this combination therapy.

overall_design: We performed RNA-seq on bone marrow-derived macrophages (BMDM) after their co-culture with LLC cells and subsequent treatment with either 100 µg/mL β-elemene or PBS for 24 hours.

first: Yongxin

last: Yu


title: Effects of a fibrate drug, bezafibrate on ascites-mediated transcriptional changes in epithelial cancer cells

status: Public on Jan 22 2026

city: Durham

first: Jen-Tsan Ashley

last: Chi

state: NC

address: 101 Science Dr

department: Molecular Genetics and Microbiology

institute: Duke University

summary: Ascites is an abnormal fluid that accumulates in the peritoneal cavity of more than 90% of patients with metastatic ovarian cancer. Despite its common occurance, little is known about its effects on detached and metastasizing ovarian cancer cells, which frequently metastasize to the peritoneum. This experiment aims to identify any transcriptional changes that occur in ovarian cancer cell lines as a result of exposure to ovarian cancer ascites and whether the fibrate drug, bezafibrate had any reversing effect on the ascites-mediated changes

overall_design: To investigate any transcriptional changes that occur in ovarian cancer cell lines as a result of exposure to ovarian cancer ascites and the fibrate drug, bezafibrate

first: Yasaman

last: Setayeshpour


title: mRNA sequencing on esophageal organoids derived from K5:Smo mice 5 days after tamoxifen injection.

status: Public on Feb 03 2026

city: Anderlecht

first: Louison

last: Descampe

address: Route de Lennik 808

department: IRIBHM

country: Belgium

institute: Université Libre de Bruxelles

summary: In our study, we used mRNA sequencing to investigate the effect of 3 days-treatment with a combination of TGFb1 and BMP with or without ibuprofen.

overall_design: mRNA profiles of esophageal organoids derived from K5:Smo mice 5 days after tamoxifen injection, treated for 72h with TGFb inhibitor / TGFb + BMP4 / TGFb + BMP4 + Ibuprofen by deep sequencing using Illumina

first: Benjamin

last: Beck

last: Dassy

first: Alizée

last: Vercauteren Drubbel


title: Effects of ascites exposure from ovarian cancer on epithelial cancer cell lines

summary: Ascites is an abnormal fluid that accumulates in the peritoneal cavity of more than 90% of patients with metastatic ovarian cancer. Despite its common occurance, little is known about its effects on detached and metastasizing ovarian cancer cells, which frequently metastasize to the peritoneum. This experiment aims to identify any transcriptional changes that occur in ovarian cancer cell lines as a result of exposure to ovarian cancer ascites

overall_design: To investigate any transcriptional changes that occur in ovarian cancer cell lines as a result of exposure to ovarian cancer ascites

first: Chi

last: Jen-Tsan Ashley

first: Setayeshpour

last: Yasaman


title: Single-cell RNA sequencing of mouse brain immune cells following peripheral SARS-CoV-2 infection

status: Public on Jan 21 2026

city: Iowa City

first: Stanley

last: Perlman

state: Iowa

address: 51 Newton Road

department: Dept of Microbiology and Immunology

institute: University of Iowa

summary: NeuroPASC, characterized by persistent neurological and neuropsychiatric symptoms, is among the most common manifestations of Post-Acute Sequelae of COVID-19 (PASC). However, the mechanisms underlying neuroPASC remain poorly understood. This dataset was generated to characterize transcriptional changes in brain immune cells following peripheral SARS-CoV-2 infection at 6, 30, and 100 days post-infection. It provides insight into the dynamic roles of brain-resident microglia and border-associated macrophages, as well as infiltrating monocytes and neutrophils, during the development and progression of neuroPASC.

overall_design: C57BL/6 mice were intranasally infected with 1000 PFU of SARS-CoV-2 N501YMA30. Brain immune cells were isolated from mock-infected mice or at 6, 30, 100 days post-infection using CD45+ magnetic beads. 4-5 mice per group were pooled together for scRNA-seq library preparation.

first: Lu

last: Tan

first: Shea

last: Lowery

first: Andrew

last: Thurman


title: Methylation-based cellular deconvolution of triple-negative breast cancer DNA reveals prognostic immune signature

status: Public on Jan 19 2026

city: Sydney

first: Sarah

last: Williams

address: 384 Victoria St, Darlinghurst

institute: The Garvan Institute of Medical Research

type: Methylation profiling by genome tiling array

summary: In triple negative breast cancer (TNBC), immune infiltration is now recognised as playing an important role in prognosis. DNA methylation, due to its cell-type specificity, offers a promising approach for quantifying immune cell abundance as a biomarker for risk stratification. Here, we used EpiDISH, a DNA methylation-based cellular deconvolution method, to estimate immune cell proportions from genome-wide methylation data across three independent cohorts, including TNBC patients. We show that increased immune cell percentage in TNBC patients specifically, was associated with longer disease-specific survival, highlighting the potential of DNA methylation-based estimates of cell composition for prognosis in TNBC.

overall_design: TNBC samples were obtained as FFPET blocks from archives of Hunter Area Pathology Service, John Hunter Hospital, Newcastle, Australia, University of Queensland and Garvan Institute of Medical Research

first: Ruth

last: Pidsley

first: Clare

last: Stirzaker


title: AURKA/PHB2 signaling drives acquired resistance to KRAS G12C inhibitors in KRAS G12C -mutant NSCLC

status: Public on Jan 17 2026

city: Fuzhou

first: xiandong

last: lin

state: fujian

address: No. 420 Fuma Road, Jinan District

institute: Fujian Cancer Hospital and Fujian Medical University Cancer Hospital

summary: Patients with non-small cell lung cancer (NSCLC) who initially respond to Sotorasib, a drug targeting the KRAS G12C mutation, eventually develop acquired resistance. However, the mechanisms driving this acquired resistance remain largely unclear. This study explored the role of AURKA in mediating resistance to Sotorasib in NSCLC. The expression levels of AURKA mRNA and protein in NSCLC cell lines (H358 and Calu-1) were assessed using qPCR and Western blot. To further elucidate the role of AURKA in the biological alterations of Sotorasib-resistant cells and its association with the PI3K/AKT signaling pathway, a comprehensive set of assays were conducted, including MTS, colony formation, Transwell migration, luciferase reporter assays, fluorescent in situ hybridization (FISH), molecular docking analyses, and immunoprecipitation. The key findings include: (1) Long-term Sotorasib treatment led to upregulation of AURKA; (2) Overexpression of AURKA induced Sotorasib resistance, suppressed apoptosis and promoted migratory potential in Calu-1 and H358 cells, while AURKA knockdown increased the sensitivity, enhanced apoptosis and inhibited migratory capacity of H358-SR and Calu-1-SR cells to Sotorasib; (3) Immunoprecipitation and luciferase reporter assays demonstrated a physical interaction between AURKA and PHB2, establishing a positive feedback loop that sustained malignant behaviors, potentially explaining how Sotorasib-resistant cells survived despite KRAS pathway inhibition; (4) AURKA stabilizes PHB2, activating the PI3K/AKT pathway and allowing cancer cells to bypass the KRAS blockade, thus restoring malignant behavior. (5) The combination of AURKA inhibitor and Sotorasib alleviates the acquired drug resistance in vitro and in vivo. These data suggest that resistance to Sotorasib in NSCLC is associated with a positive feedback loop involving AURKA, PHB2, and PI3K/AKT signaling. AURKA may serve as a biomarker for predicting the therapeutic efficacy of Sotorasib in KRAS G12C-targeted therapies and as a potential therapeutic target to overcome Sotorasib resistance in NSCLC.

overall_design: AURKA knockdown cell lines were generated using a lentiviral transduction approach. Cells were adjusted to a final concentration of 1 × 10⁶ cells/mL. Total RNA was extracted and assessed for quality and quantity by agarose gel electrophoresis and NanoDrop spectrophotometry. Poly(A)+ mRNA was enriched using oligo(dT) magnetic beads; for degraded RNA samples or prokaryotic samples, rRNA depletion kits were used instead. RNA sequencing libraries were constructed using commercial kits. Briefly, RNA was fragmented and reverse-transcribed into first-strand cDNA using random primers, followed by second-strand cDNA synthesis incorporating dUTP. The resulting double-stranded cDNA underwent end repair, A-tailing, and ligation with Illumina-compatible adapters, followed by PCR amplification to generate the final libraries. The constructed libraries were quality-checked using an Agilent 2100 Bioanalyzer, quantified by qPCR, and subsequently sequenced on an Illumina NovaSeq 6000 platform.

first: Jinrong

last: Liao

first: Xin

last: Lan

first: Zeng

last: Chen

first: Dan

last: Hu

first: Doudou

last: Luo

first: Zhiyi

last: Huang

first: Huocong

last: He

first: Yunpeng

last: Bai

first: Xingguang

first: Xiandong

last: Lin

first: Hongyu

first: Longbin

last: Zhang


title: Rapamycin Reverses the Hepatic Response to Diet-Induced Metabolic Stress That Is Amplified by Aging.

status: Public on Jan 16 2026

city: La Jolla

first: Peter

middle: D.

last: Adams

state: CA

address: 10901 North Torrey Pines Road

department: Cancer Genome and Epigenetics Program

institute: Sanford Burnham Prebys Medical Discovery Institute

summary: Aging is associated with increased susceptibility to metabolic stress and chronic liver disease, yet the interactions between age and metabolic stressors and the potential for ameliorating interventions remain incompletely understood. Here, we examined the hepatic response of young (7-month-old) and old (25-month-old) C57BL/6 male mice to a 9-week high-fat diet (HFD) and assessed whether rapamycin, a well-established pro-longevity intervention, could mitigate age-exacerbated effects. While both age groups developed metabolic-associated steatohepatitis (MASH), older mice displayed more severe hepatic steatosis, inflammation, and transcriptional dysregulation. Transcriptomic profiling of whole livers and purified hepatocytes revealed that aging amplifies HFD-induced inflammatory and metabolic gene expression changes, including activation of immune pathways and suppression of metabolic pathways. Notably, treatment of aging mice with rapamycin reversed the majority of HFD-driven transcriptional alterations, including upregulation of pro-inflammatory regulators such as Stat1, and dysregulation of metabolic gene networks. Rapamycin also reduced hepatosteatosis, total body weight, and a tumorigenic transcriptomic signature associated with hepatocellular carcinoma risk. These findings demonstrate that aging intensifies hepatic sensitivity to dietary metabolic stress and identify rapamycin as a promising therapeutic to counteract age-related liver dysfunction and metabolic dysfunction-associated steatotic liver disease (MASLD) progression.

overall_design: Three cohorts were examined: normal diet (ND) + vehicle, high fat diet (HFD, 60% calories from fat) + vehicle and high fat diet + rapamycin (42ppm). Mice were initiated on either ND + vehicle or ND + rapamycin at 4-months of age. Once mice reached 18-months of age, they were either maintained on ND + vehicle, or HFD + vehicle, HFD + rapamycin for 9-weeks. Mice were maintained until euthanized and heptocytes were isolated using 2-step perfusion protocol.

first: Aaron

last: P. Havas

first: Adarsh

last: Rajesh

first: Xue

last: Lei

last: D. Adams


title: Multi-omics profiling reveals microbiota, metabolite, lipid, and immunological heterogeneity underlying distinct pathophysiological mechanisms of age-related endotypes in type 1 diabetes

city: Hefei

first: Lanxin

last: Pan

state: Anhui

address: 96 Jinzhai Road, Baohe District

institute: The First Affiliated Hospital of University of Science and Technology of China

summary: Type 1 diabetes (T1D) is an autoimmune disease characterized by marked heterogeneity in age at diagnosis, clinical progression, and immune pathology. Increasing evidence suggests that age-related T1D endotypes may reflect distinct underlying molecular mechanisms; however, these mechanisms remain incompletely characterized at the cellular and transcriptional levels. To investigate age-associated immune heterogeneity in T1D, peripheral blood mononuclear cells (PBMCs) were collected from a selected cohort of newly diagnosed pediatric individuals with T1D and healthy controls. Single-cell RNA sequencing was performed on PBMCs from 27 individuals with T1D and 27 age- and sex-matched healthy controls to profile peripheral immune cell populations and characterize transcriptional differences associated with age-related T1D endotypes.

overall_design: PBMCs were isolated from peripheral blood samples collected from 27 individuals with type 1 diabetes and 27 age- and sex-matched healthy controls. Single-cell suspensions were processed using the 10x Genomics Chromium Single Cell 3' Reagent Kits v3.1, and sequencing libraries were generated according to the manufacturer’s instructions. Libraries were sequenced on the Illumina NovaSeq 6000 platform to generate single-cell RNA-seq data.

first: Huiling

last: Tan

first: Tong

last: Yue

first: Xueying

last: Zheng

first: Jianping

last: Weng


title: Multi-tissue DNA methylation analysis to identify an appropriate surrogate tissue for a unique neurological tissue specific to spina bifida

first: Maitreyi

last: Mazumdar

address: Department of Neurology

institute: Boston Children's Hospital & Harvard Medical School

summary:
Background: Animal models suggest a role of epigenetic mechanisms, including DNA methylation, in neural tube closure; however, studies characterizing DNA methylation profiles in nervous system tissue from humans with spina bifida are limited, In this study, we assessed DNA methylation profiles in dural tissue of infants with spina bifida, collected at the time of surgical closure of the defect, and examined whether whole blood or buccal swab are appropriate surrogate tissues, as they are more practical to collect in large-scale epidemiological studies, DNA methylation was measured in dural tissue, buccal swab, and whole blood samples collected from 27 unique infants using the Illumina Infinium MethylationEPIC BeadChip array,
Results: Correlation analysis for each CpG site comparing DNA methylation from all participants in dural tissue to DNA methylation in whole blood DNA or buccal swab DNA yielded 1,555 statistically significant associations for the whole blood analysis and 920 significant associations for the buccal swab analysis at the Bonferroni threshold of significance, We also performed paired analysis, calculating differences between tissues within each individual and then averaging differences across individuals, After accounting for multiple hypothesis testing using the FDR adjustment, 33% of CpG sites assessed were not significantly differentially methylated between dural tissue and whole blood samples, compared to the 27% of sites not differentially methylated between dural tissue and buccal swab samples,
Conclusions: These results suggest that in the absence of dural tissue, both whole blood and buccal swab samples may be considered as surrogates for dural tissue, The study warrants replication in larger groups to validate findings and may assist researchers restricted to more accessible biospecimens (i,e, blood) to further characterize epigenetic contributors to neural tube defect etiology,

overall_design:
This dataset comprises EPIC v1,0 DNAme data for 27 infants with spina bifida, where each participant provided dural tissue, buccal swab, and whole blood samples for DNAme assessment (81 total DNAme samples), DNA was extracted using the QIAsymphony DSP DNA Midi Kit (Qiagen, Valencia, CA), Dural samples were treated with EtOH to remove the OCT gel, and DNA was extracted from dural tissue samples using the DNeasy Blood and Tissue Kit (Qiagen, Valencia, CA), DNA was bisulfite converted (Zymo D5007 Kit, Zymo Research, Irvine, CA), DNA was then ampligied, fragmented, purified, and processed on Illumina Infinium MethylationEPIC BeadChips (Illumina, San Diego, CA) according to the manufacturer's instructions, Quality control of the DNAme data was perfomed with the ewastools and minfi packages in R, all samples passed the default thresholds of the control probes and had a mean detection p-values > 0,05, Data were normalized with preprocessNoob and preprocessQuantile using the minfi package, Probes were then filtered to exclude sites with detection p-values > 0,01 in at least one sample, sites mapping to the X and Y chromosomes, sites with annotated probe SNPs, and cross-reactive probes identified by Chen et al, (2013) and Pidsley et al, (2016), A total of 680,819 CpGs in 81 samples remained for downstream analysis across the tissues,
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The IDAT files have not been provided for participant confidentiality regarding the 56 rs genotyping probes present on the EPIC v1.0 array. These probes have been excluded from the submitted dataset and the raw data have thus been provided as methylated and unmethylated signal intensities with corresponding detection p-values, rather than in IDAT form.  IDAT files will be made available upon reasonable request to MM for research use.
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first: Gwen

last: Tindula

first: Sudipta Kumer

last: Mukherjee

first: Sheikh Muhammad

last: Ekramullah

first: D

last: Arman

first: Joynul

last: Islam

first: Subrata Kumar

last: Biswas

first: Md Nafaur

last: Rahman

first: Md

last: Ziauddin

first: Ansar Uddin

last: Ahmed

first: Hafiza Sultana

last: Suchanda

first: Benjamin

last: Warf

first: David

last: Christiani

first: Bernardo

last: Lemos

first: Liming

last: Liang

first: Andres

last: Cardenas


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

first: Dale

last: Garsed

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

overall_design: Genome wide DNA methylation profiling of 24 primary tumours of long-term survivors of high grade serous ovarian cancer. The Illumina Infinium MethylationEPIC BeadChip was used to obtain DNA methylation profiles across approximately 850,000 CpGs. 77 primary tumors from GSE65820 and 53 primary tumors from GSE211686 were also used in the project.

first: Tibor

last: Zwimpfer

first: Ahwan

last: Pandey

last: Bowtell


title: CTCF-mediated chromatin topology enables receptor editing to enforce a central B-cell tolerance checkpoint [ChIP-Seq_CTCF]

status: Public on Jan 15 2026

city: Jerusalem

first: Yehudit

last: Bergman

address: Ein Karem

department: Department of Developmental Biology and Cancer Research

country: Israel

institute: The Hebrew University Of Jerusalem

summary: The generation of a diverse yet self-tolerant B cell repertoire is fundamental to adaptive immunity and is achieved through the ordered process of V(D)J recombination. In mice, Igκ represents the dominant light chain, while Igλ rearrangement serves as a secondary response to nonproductive or autoreactive Igκ recombination — a process known as receptor editing. Recombination at the RS element deletes the Igκ constant exon, silencing the locus and enabling Igλ expression. Yet the epigenetic regulatory framework that orchestrates this critical tolerance checkpoint in immature B cells remains unresolved. Here, we identify a CTCF-binding element (CBE) embedded within the 3′-Igκ super-enhancer (3′-SEκ) that governs receptor editing and directs the κ-to-λ switch essential for Igλ⁺ B cell development in vivo. Mechanistically, deletion of this insulator element abrogates chromatin looping essential for receptor editing and concomitantly activates a latent enhancer program within the 3′-SEκ, driving aberrant Vκ recombination and rewiring Igκ chromatin architecture through disrupted CTCF boundary function. Notably, loss of this CBE swiftly leads to elevated autoantibody production, demonstrating that CBE-mediated chromatin architecture shapes B cell fate by constraining autoreactivity. Collectively, these findings establish CTCF-dependent chromatin topology as a checkpoint that couples three-dimensional genome organization with antigen-driven receptor editing, to establish self-tolerance.

overall_design: CTCF ChIP-seq was carried out on IL-7–cultured pre-B cells isolated from 6–12-week-old WT and ΔrsCBE mice

last: Gomes

first: Merav

last: Hechst

first: Eliraz

last: Gitelman


title: CTCF-mediated chromatin topology enables receptor editing to enforce a central B-cell tolerance checkpoint [Micro-C-TALE]

overall_design: Micro-C-TALE sequencing was performed on ex vivo CD19⁺ pre-B cells isolated from 6–12-week-old WT-Rag1⁻/⁻.hIgM and ΔrsCBE-Rag1⁻/⁻.hIgM mice.

first: Anna

last: Golberg

first: Noam

last: Kaplan


title: NanoString Breast Cancer 360 expression profiling of histologically normal breast lobules from NHBW and NHWW donors (BC360)

status: Public on Feb 02 2026

city: Jacksonville

first: Derek

middle: Charles

last: Radisky

state: Florida

address: 4500 San Pablo Road

department: Cancer Biology

institute: Mayo Clinic

summary: Histologically normal breast lobules were obtained from non-Hispanic Black women (NHBW) and non-Hispanic White women (NHWW) (n=10 per group) matched by age, BMI, and parity. RNA extracted from FFPE sections was profiled using the NanoString Breast Cancer 360 CodeSet to characterize transcriptional programs associated with group differences in benign breast epithelium.

overall_design: Twenty histologically normal breast lobule samples (10 NHBW, 10 NHWW) were profiled on the NanoString Breast Cancer 360 panel. Raw RCC files are provided along with normalized expression values.

first: Joshua

last: Ogony


title: CTCF-mediated chromatin topology enables receptor editing to enforce a central B-cell tolerance checkpoint [RNA-seq_IGK repertoire]

overall_design: Genome-wide RNA profiling of exvivo small pre-B cells derived from C57Bl6 WT, ΔrsCBE, and ΔrpiaCBE mice of 6-12 weeks of age

first: Avidov

last: Bar


title: CTCF-mediated chromatin topology enables receptor editing to enforce a central B-cell tolerance checkpoint [RNA-seq]

overall_design: Genome-wide RNA profiling was performed on ex vivo small pre-B cells isolated from 6–12-week-old C57BL/6 WT and ΔrsCBE mice.


title: CTCF-mediated chromatin topology enables receptor editing to enforce a central B-cell tolerance checkpoint [4C-Seq]

overall_design: 4C sequencing was performed on v-Abl–transformed 445.3 Rag1-deficient pro-B cells from WT, rsCBE-571 bp–deleted, ΔSIS 445.3, and rsCBE-18 bp–deleted lines.


title: Integration protocol of microglia and cerebral organoid

first: Yukyeong

last: Lee

address: 185 Cambridge Street

institute: MGH

summary: sample analysis by an integrated protocol to induce microglia and neurons

first: Rakesh

last: Karmacharya


title: Melittin enhances PD-L1 blockade in prostate cancer by inhibiting M2 macrophage polarization and recruitment

status: Public on Jan 14 2026

city: Shanghai

first: Rucheng

last: Yan

address: 1800,yuntai road

institute: Shanghai East Hospital

summary: Objective: The immunosuppressive tumor microenvironment (TME) limits the efficacy of immunotherapy in prostate cancer treatment. This study aims to investigate how melittin remodels the TME in prostate cancer and enhances the response mechanism to anti-PD-L1 therapy. Methods: The anti-tumor efficacy of melittin was evaluated in a C57BL/6J mouse prostate cancer model. An in vitro co-culture model of prostate cancer cells (PC-3, 22RV1) and THP-1-derived macrophages was established. RNA sequencing, flow cytometry, qPCR, Western blot, ELISA, Transwell migration assays, and immunohistochemistry were employed to explore the anti-tumor mechanisms of melittin. The synergistic effect of combining melittin with an anti-PD-L1 antibody was assessed in vivo. Results: Melittin significantly inhibited tumor growth in vivo. It remodeled the TME by increasing CD8⁺ T cell infiltration and reducing macrophage numbers. Furthermore, melittin specifically inhibited M2 macrophage polarization, downregulating the expression of CD206, CD163, and TGF-β, an effect potentially mediated through inhibition of the JAK-STAT pathway. Additionally, melittin reduced macrophage recruitment by downregulating tumor-derived CCL2. Combination therapy using melittin and anti-PD-L1 antibody demonstrated synergistic anti-tumor effects, significantly reducing tumor volume and weight, decreasing intratumoral expression of Ki67 and PD-L1, and enhancing CD8⁺ T cell infiltration. Conclusion: Melittin reverses the immunosuppressive TME in prostate cancer by simultaneously inhibiting JAK-STAT-mediated M2 polarization and CCL2-dependent macrophage recruitment. This reprogramming of the TME, combined with PD-L1 blockade, offers a novel combination immunotherapy strategy for prostate cancer.

overall_design: THP-1 cells were differentiated with 100 ng/ml PMA for 48 h in the lower chamber of a Transwell system. Tumor cells were then seeded in the upper chamber and co-cultured with 3 μg/mL melittin for 48 h before.The induced macrophages were usd to RNA-seq.


title: Spatially resolved m6A profiling using m6A-ARTR-DBiT [spatial]

city: Chicago

first: Chuan

last: He

state: Illinois

address: 929 E 57th St., GCIS E319

institute: The University of Chicago

type: Methylation profiling by high throughput sequencing

summary: N6-methyladenosine (m6A) on RNA plays diverse regulatory roles, yet its spatial distribution within tissues remains largely unexplored. Here we introduce m6A-ARTR-DBiT, a spatial m6A profiling assay that leverages reverse-transcription-based detection and deterministic barcoding in tissue to map transcriptome-wide m6A distribution while preserving native tissue context. Applying m6A-ARTR-DBiT to mouse embryonic tissues and adult brains generates spatially resolved m6A landscapes and reveals region-associated m6A features across different functional domains. Pairwise comparison of spatial m6A profiles with spatial transcriptomes uncovers positive correlations between m6A levels and the expression of its methyltransferases and binding proteins, which also enables systematic identification of tissue-region-specific epitranscriptomic regulation. In the mouse hippocampus, m6A-ARTR-DBiT allows for high-resolution mapping of m6A organization within fine-scale tissue structures. Together, m6A-ARTR-DBiT provides a platform for interrogating RNA modification distribution within intact tissue sections, offering insights into the link between spatially patterned m6A deposition and gene regulation.

overall_design: We developed an m6A profiling assay leveraging reverse transcription and deterministic barcoding in tissue (m6A-ARTR-DBiT) for spatial exploration of m6A modifications. We benchmarked this method on cell lines, demonstrating its capability to detect m6A modifications, and further applied m6A-ARTR-DBiT to mouse embryonic and brain tissues to generate high-resolution, whole-transcriptome spatial m6A maps.

first: Yu

last: Xiao

first: Zhiliang

last: Bai

first: Rong

last: Fan


title: RNA-seq profiling of METTL1 knockdown in human intestinal epithelial FHC cells

status: Public on Jan 12 2026

city: Changsha

first: Lichao

last: Yang

state: Hunan

address: renmin middle road

institute: The Second Xiangya Hospital, Central South University

summary: METTL1 is a key methyltransferase responsible for N7-methylguanosine (m7G) modification of RNA and has been implicated in multiple cellular processes. However, its role in human intestinal epithelial cells remains incompletely understood.               In this study, we performed RNA sequencing (RNA-seq) to characterize transcriptomic changes induced by METTL1 knockdown in human fetal intestinal epithelial (FHC) cells. Stable METTL1 knockdown was achieved using lentiviral short hairpin RNA (shRNA), while control cells were infected with a non-targeting control shRNA lentivirus (sh-Ctrl). Knockdown efficiency was validated prior to sequencing.                                       Total RNA was extracted from METTL1-knockdown and sh-Ctrl FHC cells, with three independent biological replicates per group. This dataset provides a transcriptomic resource for investigating the regulatory role of METTL1 in intestinal epithelial cells.

overall_design: Human fetal intestinal epithelial FHC cells were divided into two groups: METTL1 knockdown and shRNA control. Lentiviral shRNA targeting METTL1 (sh-METTL1) was used to stably suppress METTL1 expression in FHC cells, while control cells were infected with a non-targeting control shRNA lentivirus (sh-Ctrl). After confirmation of knockdown efficiency, total RNA was extracted and subjected to high-throughput RNA sequencing. Each group consisted of three independent biological replicates. Differential gene expression analysis was performed to identify transcriptional changes associated with METTL1 depletion.

first: Lianwen

last: Yuan


title: Spatially resolved m6A profiling using m6A-ARTR-DBiT

first: Zhuoning

last: Zou


title: Manual curation for improved genome annotation of the functionally extinct northern white rhinoceros (Ceratotherium simum cottoni)

city: Escondido

first: Elena

last: Ruggeri

address: 15600 San Paqual Valley Rd.

institute: San Diego Zoo Wildlife Alliance

summary: The northern white rhinoceros (Ceratotherium simum cottoni) genome and annotation were previously published, but the annotation contained few genes, with many annotation misalignments, and nomenclature not matching HGNC/VGNC naming conventions, making transcriptional studies very difficult. We used in vivo collected granulosa cells for RNA sequencing and de novo transcript assembly through StringTie to identify all nucleotide gene sequences in our samples. Through extensive manual curation we were able to generate a greatly improved genome annotation increasing gene numbers by 81%. This will greatly enable researchers in this field to utilize the genome and annotation to complete transcriptional studies with this species.

overall_design: Transcriptomic of SWR GC from follicles in different stages of development.

first: Ruggeri

last: Elena

first: Prunier

last: Julien

first: Marc-André

last: Sirard

first: Durrant

last: Barbara

first: Klohonatz

last: Kristin


title: Dual Mechanisms of Supporting Cell Regeneration in the Neonatal Mouse Cochlea

city: Stanford

first: Alan

last: Cheng

address: 240 Pasteur Drive

institute: Stanford University

summary: Cochlear supporting cells are critical for proper hearing function and regeneration of hair cells, which are responsible for perceiving sound in the inner ear. In the neonatal mouse cochlea, when supporting cells are ablated, they can regenerate through progenitor cells in the cochlea. Here, we show through single cell RNA sequencing and in vivo fate mapping, that upon supporting cell ablation in the neonatal cochlea, inner phalangeal cells regenerate through two independent mechanisms; one which requires proliferation and the other by which transdifferentiation (i.e. regeneration without mitotic division) of cochlear progenitor cells occurs. These dual mechanisms are spatially distinct where transdifferentiation occurs in all three turns of the cochlea, while proliferation-induced regeneration occurs exclusively in the apical and middle turns. Inhibiting proliferation using aphidicolin, slightly decreased the number of regenerated IPhCs in the apex middle turns, but not the base, after damage. We also observed a medial to lateral transition in the compartmentalization of the GER after supporting cell damage, suggesting de-differentiation of these domains. Overall, our study reveals GER cells as supporting cell progenitors that undergo dual mechanisms of regeneration (mitotic and non-mitotic). Additionally, we uncover transcriptomic changes after supporting cell damage in the neonatal mouse cochlea that could be used as gene targets in therapies for hearing loss.

overall_design: Whole cochlea from postnatal days (P) 4, P5, P6 and P7 Ki67CreERT/+;Lgr5DTR/+;Rosa26RtdTomato/+ (damage) and Ki67CreERT/+;Rosa26RtdTomato/+ (control) mice were dissociated in biological duplicate for single cell RNA-sequencing. Cells were processed using 10X Genomics Chromium Single Cell 3' Reagents v3.1. After sequencing, Cell Ranger was used for read mapping and quantification, followed by further analysis using Seurat.

first: Julia

last: Abitbol

first: Maggie

last: Matern


title: 5′ UTR length shapes alternative N-terminal protein isoforms across cancers and in rare disease

city: Cambridge

first: Jimmy

last: Ly

state: Massachusetts

address: 455 main street

institute: Whitehead Institute

summary: The 5′ untranslated region (5′ UTR) of an mRNA is classically viewed as a regulatory region that controls the amount of protein production, but not the resulting protein sequence. Here, we demonstrate that 5′ UTR length also plays a direct role in alternative N-terminal protein isoform production by controlling start codon selection. We find that very short 5′ UTRs enhance leaky scanning, thereby promoting the production of truncated alternative N-terminal protein isoforms. Changes in 5′ UTR length due to alternative transcription initiation can tune the relative abundance of alternative N-terminal isoforms from the same gene. In addition, we identify mutations in rare genetic diseases that alter 5′ UTR length, including a deletion in the VHL 5′ UTR in von Hippel–Lindau disease that shifts translation toward the shorter VHLp19 isoform. Together, our results implicate 5′ UTR length as a determinant of alternative N-terminal isoform production and reveal an underappreciated mechanism by which noncoding mutations can reshape the proteome.

overall_design: Whole cell RNA was extracted from asynchronously growing HeLa cells and CAGE-Seq was performed on the resulting mRNA.

first: Iain

last: Cheeseman


title: Strongly regulated “super-target” transcription factors exert an outsized influence in microRNA-regulated networks

city: Adelaide

first: Katherine

middle: Anne

last: Pillman

state: SA

address: North Terrace

department: Centre for Cancer Biology

institute: Adelaide University

summary: To elucidate the role of microRNAs (miRNAs), it is essential to identify their direct post-transcriptional targets. However, identifying the most functionally significant targets is challenging due to factors such as the inherent limitations of predictive algorithms, the abundance of RNA interactions detected in co-precipitation studies, and the prevalence of non-productive targeting caused by weak interactions or unfavorable stoichiometries. We introduce the concept of 'super-targets'—genes whose regulation disproportionately drives miRNA functionality by virtue of both strong targeting and the critical role of the gene itself, such as a transcription factor whose disruption has broad downstream effects. A prime example is the reciprocal regulation between the miR-200 family and ZEB transcription factors, which governs the epithelial-mesenchymal status of cells. To assess the impact of such 'super-targeting,' we developed a system that isolates ZEB regulation from all other miR-200 activities. This approach reveals a complex network of transcriptional and post-transcriptional regulation, where miR-200’s ability to maintain an epithelial phenotype and suppress cell migration is fully dependent on the repression of ZEB1 and ZEB2, though other effects are ZEB-independent. Our findings suggest that a significant portion of miRNA regulatory impact may result from the potent targeting of a few key genes, highlighting that indirect transcriptional effects are a fundamental mechanism of miRNA function and likely more impactful than numerous modestly-regulated direct targets that otherwise dominate the publication landscape.

overall_design: RNA-seq profiling of wild-type MDA-MB-231 cells and their derivatives with DOX-inducible ZEB1 and ZEB2 expression constructs (lacking 3'UTRs and thus, insensitive to miR-200 mediated repression).  miR-200c or control miRNAs were co-transfected.

first: Julie

last: Bracken

first: Laura

last: Sourdin

first: Gregory

last: Goodall

first: Cameron

middle: P


title: Effect of Meflin overexpression on the fibroblast transcriptome in a three-dimensional culture using cell accumulation technique

status: Public on Jan 11 2026

city: Nagoya

first: Akihiro

last: Sakai

state: Aichi

institute: Nagoya university

summary: We previously reported that Meflin, encoded by the immunoglobulin superfamily containing leucine-rich repeat (ISLR) gene, is a marker for tumor-restraining cancer-associated fibroblasts. However, the functional roles of Meflin in fibroblasts remain unclear. To investigate the functional impact of Meflin expression in fibroblasts, RNA sequencing was performed on Meflin-overexpressing NHDF-Ad cells cultured under conditions that better mimic the in vivo tumor microenvironment, using a cell accumulation technique that accurately recapitulates the fibrotic stroma observed in aggressive human cancers. Meflin overexpression resulted in the downregulation of PDPN, a well-established marker of tumor-promoting CAFs, and upregulation of DPT and COL15A1, which are markers of universal fibroblasts that resemble normal fibroblasts and are considered a potential source of diverse fibroblast subtypes.These findings suggest that high-level expression of Meflin is crucial for skewing CAFs toward a more universal fibroblast–like state.

overall_design: RNA-seq profiling of Meflin-overexpressing NHDF-Ad cells and control NHDF-Ad cells cultured either alone or co-cultured with MDA-MB-468, a triple-negative breast cancer cell line, in a three-dimensional culture system using the cell accumulation technique.

first: Shinji

last: Mii

first: Atsushi

last: Enomoto


title: Genetic inactivation of the Translin/Trax RNase activity alters small RNAs including miRNAs, disrupts gene expression and impairs distinct forms of hippocampal synaptic plasticity and memory

status: Public on Jan 10 2026

first: Junko

last: Kasuya

state: IA

address: 169 Newton Rd

department: Neuroscience and Pharmacology

institute: University of Iowa

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

overall_design: Refer to individual Series


title: Genetic inactivation of the Translin/Trax RNase activity alters small RNAs including miRNAs, disrupts gene expression and impairs distinct forms of hippocampal synaptic plasticity and memory [Trax microRNAseq]

summary: Neurons utilize RNA interference in the reversible translational repression of synaptically localized mRNAs, enabling rapid translation in response to synaptic activity. Two evolutionarily conserved proteins, Translin and Trax, form an RNase complex which processes miRNAs, tRNAs and siRNAs. To determine the specific role of the RNase activity of this complex in brain function, we employed a mouse line harboring a point mutation in Trax (E126A) that renders the Translin/Trax RNase inactive. At the molecular level, we found alterations in the levels of multiple small RNAs including miRNAs, tsRNAs and substantial downregulation of gene expression at the mRNA level in the hippocampus of TraxE126A mice. At the synaptic level, TraxE126A mice exhibit deficits in specific forms of long-term hippocampal synaptic plasticity. At the behavioral level, TraxE126A mice display impaired long-term spatial memory and altered open-field and acoustic-startle behavior. These studies reveal the functional role of Translin/Trax RNase in the mammalian brain.

overall_design: hippocampal microRNA-seq profiling of 14-17 weeks old Trax[E126A] mutant mice was compared to their control littermates.

first: Mahesh

last: Shetty

first: Xiuping

last: Fu

first: Marisol

last: Lauffer

first: Satya

middle: M

last: Tadinada

first: Tania

last: Chatterjee Chowdhury

first: Jay

last: Baraban

first: Ted

last: Abel


title: RNA-seq of PRSS23 knockdown in ovarian cancer cell lines JHOC-5 and OVCA420

status: Public on Jan 07 2026

first: Derek

last: Radisky

summary: Bulk RNA-seq was performed in ovarian cancer cell lines JHOC-5 and OVCA420 after lentiviral PRSS23 knockdown using two independent shRNAs (shRNA_30 and shRNA_46) or a non-targeting shRNA control. Gene-level read counts for all samples are provided.

overall_design: 2 cell lines (JHOC-5, OVCA420) × 3 conditions (non-targeting control, PRSS23 shRNA_30, PRSS23 shRNA_46) × 2 biological replicates (12 libraries total).


title: Genetic inactivation of the Translin/Trax RNase activity alters small RNAs including miRNAs, disrupts gene expression and impairs distinct forms of hippocampal synaptic plasticity and memory [Trax bulk mRNAseq]

overall_design: Hippocampal mRNA-seq profiling of 14-17 weeks old Trax[E126A] mutant was compared to their control littermates.


title: An ERF transcription factor StPti5, a novel regulator of endophyte community maintenance in potato

status: Public on Jan 06 2026

city: Madrid

first: Jose M.

last: Franco-Zorrilla

state: Madrid

address: Darwin, 3

department: Plant Molecular Genetics

country: Spain

institute: Centro Nacinal de Biotecnologia-CSIC

summary: We have recently identified an ethylene response factor, StPti5, as a susceptibility factor that negatively regulates immune response to diverse pathogens. Here, we investigated the processes involved in colonisation of potato with beneficial organisms.  RNA-seq showed that at the time of Bacillus subtilis biofilm establishment, immune responses in interacting roots were attenuated, and complex transcriptional network was triggered, with ethylene signalling being a central module and StPti5 strongly induced. Interestingly, the response is intensified if plants are inoculated by two antagonistic B. subtilis strains.  While StPti5 is not involved in the establishment of biofilm on roots, we show that bacterial abundance increases in shoots of StPti5-silenced plants. Remarkably, root colonization by the arbuscular mycorrhizal fungus Rhizophagus irregularis was also higher in the StPti5-silenced plants.  StPti5 is involved both in suppressing defence against harmful and limiting colonisation with beneficial microbes. Such mechanistic understanding of plant–microbe interaction paves the way for sustainable crop management.

overall_design: DAP-seq experiments

first: Franco Zorrilla

last: José Manuel

first: Álvarez

last: Eva

first: Gruden

last: Kristina

first: Levak

last: Valentina


title: Dynamics of Stage-specific Immune Remodeling by Neutrophils and Macrophages in Acute Lung Injury

status: Public on Jan 05 2026

city: chengdu

first: zeng

last: wanqin

state: chengdu

address: No17 renming

institute: Sichuan University

summary: Acute lung injury (ALI) is driven by dysregulated alveolar immune responses. While granulocytes and macrophages are critical effectors, their coordinated molecular reprogramming remains poorly defined. However, the evolving crosstalk and stage-specific functional transitions of these populations have been overlooked. Here, we performed single-cell RNA sequencing (scRNA-seq) of bronchoalveolar lavage fluid from intermediate and late-stage ALI patients to map immune microenvironment remodeling. We observed pronounced granulocyte expansion coupled with macrophage depletion. Granulocytes exhibit distinct trajectories from acute migratory states toward pro-inflammatory, metabolically reprogrammed subsets, dominated by TNF and MAPK signaling. Simultaneously, macrophages transition toward inflammatory M1-like phenotypes, characterized by distinct metabolic reprogramming and reduced oxidative phosphorylation. Furthermore, we identify a granulocyte-centric inflammatory network mediated through TNF, IFN, and RESISTIN pathways, establishing pathogenic feedback loops. Collectively, this study elucidates the transcriptional and metabolic reprogramming driving ALI progression, providing a framework for stage-adapted therapeutic interventions to restore pulmonary homeostasis.

overall_design: We conducted  single-cell RNA sequencing (scRNA-seq) of bronchoalveolar lavage fluid from intermediate and late-stage ALI patients


title: RNA-seq analysis of QRICH1 knockdown in Huh7 cells

status: Public on Jan 04 2026

city: Seoul

first: Su-Yeon

last: Park

state: National Research Foundation of Korea

address: Cancer Molecular Targeted Herbal Research Center, College of Korean Medicine, Kyung Hee University, 1 Hoegi-dong, Dongdaemun-gu, Seoul 02447, South Korea

country: South Korea

institute: Kyung Hee University

summary: This study investigates the transcriptomic changes following QRICH1 knockdown in Huh7 hepatocellular carcinoma cells using RNA sequencing.

overall_design: This study includes RNA-seq profiling of Huh7 hepatocellular carcinoma cells under two experimental conditions: siControl and siQRICH1 knockdown. Biological replicates were generated for each condition, and differential gene expression analysis was performed to investigate transcriptional changes associated with QRICH1 depletion.


title: A Porcine Model of Intervertebral Disc Injury Recapitulates Human Discogenic Pain via Notochordal Cell Loss and Pain-inducing Nucleus Pulposus Cell Emergence

status: Public on Jan 01 2026

city: Los Angeles

first: Dmitriy

last: Sheyn

address: 127 S San Vicente Blvd

institute: Cedars-Sinai Medical Center

summary: Lower back pain (LBP) is one of the most common causes of disability, with up to 40% of LBP cases attributed to intervertebral disc (IVD) degeneration. While small animal models are widely used to study IVD and LBP, the small size of their IVDs limits translational and biological relevance. Large animal models more accurately emulate human disease; however, methods of measuring LBP are not well established. Pigs were also considered unfit for LBP research, due to notochordal cells (NCs) persistence through life, unlike humans. We developed a comprehensive porcine model with quantitative measure of discogenic pain via biobehavioral testing (BBT), MRI, and multi-omics tissue analysis of IVD and DRGs. MRI demonstrated the progression of IVD degeneration beginning at 4 weeks post-injury. BBTs showed the development of significant pain responses by week 4 post-injury, supported by transcriptomics of injury matched DRGs. Single cell transcriptomics, trajectory and cell-cell communication analyses suggest that, with injury, NCs are differentiating to nucleus pulposus cells (NPCs). Furthermore, NPCs showed upregulation of cellular stress, neural outgrowth, and inflammation pathway, consistent with pain-inducing distress signals found in human samples. This study establishes novel MRI and BBT-based methods for quantifying LBP in pigs and supports its translational relevance to human discogenic LBP. The identification of LBP-associated clusters mirrors our previous finding in humans. Moreover, the shift of NC to NPC phenotype further supports that the porcine model is relevant to human pathology, as the injury induced accelerated aging and loss of NCs with IVD degeneration and discogenic pain.

overall_design: We performed performed a percutaneous needle puncture of lumbar discs under fluoroscopic guidance in female Yucatan minipigs. Degeneration and pain development were assessed longitudinally via MRI and biobehavioral testing. At 12 weeks post-injury, dorsal root ganglia (DRG) and IVD tissues were collected for bulk RNA-seq, and nucleus pulposus (NP) samples from injured and non-injured discs were harvested at 16 weeks for single-cell RNA-seq. Additional analyses included histology, immunofluorescence, proteomics, and serum biomarker quantification by ELISA. Integrated statistical analyses were performed to correlate imaging, behavioral, and molecular readouts of discogenic pain.

first: Kaneda

last: Giselle

first: Wechsler

last: Jacob

first: Chavez

last: Melissa

first: Sheyn

last: Julia

first: Cheema

last: Karandeep

first: Shen

last: Chushu

first: Rigo De Righi

last: Dante

first: Avalos

last: Pablo

first: Xie

last: Yibin

first: Tawackoli

last: Wafa

first: Floyd

last: Candace

first: Li

last: Debiao

last: Dmitriy


title: PARTAGE: Parallel analysis of replication timing and gene expression

city: Minneapolis

first: Quinn

last: Dickinson

state: MN

address: 100 Church Street SE

institute: University of Minnesota

summary: The human genome is partitioned into functional compartments that replicate at specific times during the S-phase. This temporal program, referred to as replication timing (RT), is co-regulated with the 3D genome organization, is cell type-specific, and changes during development in coordination with gene expression. Moreover, RT alterations are linked to abnormal gene expression, genome instability, and structural variation in multiple diseases, including cancer. However, mechanistic links between RT, large-scale 3D genome architecture, and transcriptional regulation remain poorly understood. A major limitation is that current approaches require the separate profiling of RT and transcriptomes from independent batches of samples, obscuring the complex co-regulation between the epigenome and transcriptome. Here, we developed PARTAGE, a multiomics approach that enables joint profiling of copy number variation (CNV), RT, and gene expression from the same sample, providing a more accurate integrative view of the complex relationships between RT and gene regulation.

overall_design: A novel multiomics approach for simultaneous analysis of RT and gene expression. We have collected cells at distinct stages of the cell cycle under conditions that preserve both nucleic acids, enabling joint profiling of RT (Repli-seq) and transcriptomes (RNA-seq).

first: Lakshana

last: Sruthi Sadu Murari

first: Silvia

last: Meyer-Nava

first: Juan Carlos

last: Rivera-Mulia


title: The PAR2/TRPV3/IL-33 Axis in Keratinocytes Drives Neuroimmune

city: Beijing

first: Zhou

last: Lingxuan

address: No. No.8, Xishiku Street, Xicheng District, Beijing

institute: Peking university first hospital

summary: Epidermal transient receptor potential (TRP) channels are involved in complex interactions between the peripheral nervous system and the immune system in atopic dermatitis (AD). Recently, we identified that TRPV3 interacts with protease-activated receptor 2 (PAR2) to mediate non-histaminergic itch. However, the downstream molecular mechanisms following TRPV3 activation in keratinocytes remain unclear.This study aims to investigate whether TRPV3 channels regulate mast cells in the context of AD.

overall_design: We developed a range of TRPV3 conditional knockout (cKO) mice and assessed the role of TRPV3 in mast cell density and migration. Additionally, we performed RNA sequencing analyses and used genetically encoded fluorescent sensor to investigate the downstream cytokines of the TRPV3-PAR2 pathway.

first: Jiahui

last: Zhao

first: Lingxuan

last: Zhou

first: Chenyu

last: Wang

first: Ziyan

last: Rao

first: Xiaohui

last: Yuan

first: Jun

last: Cui

first: Dongyu

first: Ying

last: Sun

first: Yan

last: Chen

first: Ruoyu

last: Li

first: Miao

last: Jing


title: The miR4261/PAMM axis in multiple myeloma promotes bone resorption

status: Public on Dec 31 2025

city: Taiyuan

first: Jiangxia

last: cui

address: xinjian road

institute: Shanxi Natural Science Foundation of China

summary: Myeloma bone disease (MBD) affects ~80% of multiple myeloma (MM) patients and remains a major cause of morbidity despite anti-resorptive therapies. Here we identify a previously unrecognized exosome-mediated mechanism by which MM cells directly promote osteoclastogenesis. Tumor-derived exosomal miR-4261 is transferred to monocyte precursors, directly targets and represses PAMM (PRXL2A/FAM213A)—an antioxidant protein that negatively regulates osteoclast differentiation—and thereby accelerates osteoclast formation and bone resorption. In two independent MM cohorts, serum exosomal miR-4261 was significantly elevated in patients with MBD, whereas PAMM expression was reduced; low PAMM strongly correlated with hypercalcaemia. PAMM knockdown recapitulated the pro-osteoclastogenic effects of miR-4261, and RNA-seq/GSEA revealed selective downregulation of negative regulators of osteoclast differentiation (including TNFAIP6, CCL3, and TLR3). These findings establish the miR-4261/PAMM axis as a novel driver of myeloma-induced bone destruction and suggest serum exosomal miR-4261 as a promising liquid-biopsy biomarker and therapeutic target in MBD.

overall_design: Comparative RNA-seq analysis between control Scrambled and shPAMM cells in wild-type THP-1 cells.

first: Sicheng

last: Bian

first: Zhuanghui

last: Hao

first: Xialin

last: Zhang

first: Chen

first: Yun

first: Xiuyan

first: Hongwei


title: RNA-seq of  colon

city: Fuzhou

first: Qingxiang

last: Gao

state: FuJian

address: Qiuyang Road No1.

institute: Fujian University of Traditional Chinese Medicine

summary:
Objective: Inflammatory bowel disease (IBD), encompassing ulcerative colitis (UC) and Crohn’s disease (CD), represents a challenging group of chronic gastrointestinal inflammatory disorders. While trained immunity, a form of innate immune memory, has shown promise in combating infection and cancer, its role in chronic inflammatory diseases, particularly inflammatory bowel disease (IBD), remains relatively underexplored. This study aims to investigate the potential of trained immunity to ameliorate IBD.
Results: BG induced trained immunity significantly ameliorates DSS-induced colitis. Mechanistically, β-glucan primed the hematopoietic compartment, leading to a profound shift in monocyte fuction. Both bone marrow transplantation from trained donors to naïve recipients and adoptive transfer of trained peripheral monocytes provided protection against DSS colitis. Notably, trained mice displayed enhanced bactericidal activity against intestinal bacterial infections. Furthermore, single-cell RNA sequencing revealed that β-glucan-induced trained immunity resulted in an expansion of reparative Cx3cr1 intestinal macrophages originating from Ly6Chi monocytes, facilitating faster recovery of the colon epithelium.
Conclusion: Our findings demonstrate that β-glucan effectively induces trained immunity, leading to a multifaceted protective response against experimental colitis. These findings provide compelling evidence for the therapeutic potential of harnessing trained immunity to treat IBD and offer a novel approach to modulating intestinal inflammation and restoring gut homeostasis.

overall_design: RNA sequencing on colonic samples collected at multiple time points following DSS administration.

first: Yinyin

last: Lv

first: Qiongyun


title: Contact with smooth muscle cells dictates the endothelial transcriptome

city: Charlottesville

first: Brant

last: Isakson

state: Virginia

department: Cardiovascular Research Center

institute: University of Virginia

summary: The phenotypes of endothelial cells (ECs) in conduit and resistance arteries differ in part due to the presence of myoendothelial junctions in resistance arteries. These are direct contact points between ECs and smooth muscle cells (SMCs) that form through holes in the inner elastic lamina. To investigate the consequences of SCM contact on endothelial phenotypes, we used transwells to culture ECs in three conditions: cultured without SMCs (monolayer ECs), co-cultured without direct contact with SMCs (no-contact ECs), and co-cultured with SMCs such that myoendothelial junctions could form (contact ECs). We then collected the ECs and performed bulk RNA sequencing. These data demonstrate the impact of SMC-derived signals on endothelial phenotypes.

overall_design: To model resistance arteries, endothelial cells were cultured following the vascular cell co-culture model as previously reported. Briefly, human coronary artery smooth muscle cells (SMCs) were plated (75,000 cells/well) on the bottom of a 6-well plate or on the underside of the transwell. The following day, human coronary artery ECs were seeded on the top side of the transwell. An additional group of ECs were plated in a transwell dish without smooth muscle cells. In all three conditions, endothelial cell growth media MV (Promocell) was placed on the top of the transwell and SMC media (Lonza) was placed in the bottom chamber of the transwell. Two days after plating ECs, the media was changed, and ECs were collected the following day. For transcriptomics, RNA was isolated using Quick-RNA MiniPrep (Zymo Research). PE150 reads were generated with the Illumina NovoSeq platform. The paired-end reads were mapped to the hg38 reference genome using STAR (v2.7.9a). Gene counts were generated with featureCounts in the Subread package. For all datasets, DESeq2 (v1.34.0) was used to identify differentially expressed genes (DEGs) (Padj < 0.05). Ensemble IDs were converted to gene symbols using the org.Hs.eg.db package.

first: Luke

last: Dunaway


title: Iron chelation shifts endothelial phenotypes

summary: Iron deficiency is a highly prevalent nutrient deficiency and the most common cause of anemia. Although iron deficiency exacerbates cardiovascular disease, the direct impact of iron deficiency on the vasculature remains unstudied. Human lymphatic and arterial endothelial cells were treated with deferoxamine for 24 hours to assess the impact of iron deficiency on endothelial cell phenotypes. We found iron chelation upregulated the expression of arterial makers in both cell types. In lymphatic endothelial cells, iron chelation decreased the expression of lymphatic markers. These data suggest iron chelation shifts endothelial cells toward an arterial phenotype.

overall_design: To deplete iron, human coronary artery ECs and human dermal lymphatic ECs were grown to confluence and treated with 100 mM deferoxamine (DFO; MedChemExpress) for 24 hours. RNA was isolated with Quick-RNA MiniPrep (Zymo Research). PE150 reads were generated with the Illumina NovoSeq platform. The paired-end reads were mapped to the hg38 reference genome using STAR (v2.7.9a). Gene counts were generated with featureCounts in the Subread package. For all datasets, DESeq2 (v1.34.0) was used to identify differentially expressed genes (DEGs) (Padj < 0.05). Ensemble IDs were converted to gene symbols using the org.Hs.eg.db package.