title: Early transcriptional responses post-recanalization in a mouse model of middle cerebral artery occlusion

city: Edmonton

first: Truong An

last: Bui

state: Alberta

address: 8440 112 Street NW

department: Psychiatry

institute: University of Alberta

summary:
Ischemic stroke is a leading cause of death and disability worldwide. Recanalization therapies for acute ischemic stroke, which include mechanical thrombectomy and rt-PA delivery, are limited as while the operations are successful, many patients experience poor clinical outcomes, termed futile recanalization. Using the murine middle cerebral occlusion (MCAO) model that mimics a large vessel occlusion with recanalization, we performed a comprehensive microarray analysis of blood samples post-MCAO and recanalization in male, female, young adult, and aged mice (N=44). Downstream bioinformatics analysis was then performed in RStudio. We discovered 11 hub genes that are potential genomic markers of early recanalization changes in mice. Vcan, a novel marker, is highly conserved and elevated in mice, rats, and clinical patients. Leukocyte and neutrophil functional activities have significant enrichment in both mice and humans. We identified a range of miRNAs that potentially regulated recanalization responses and NFE4 and MTF1 as the primary transcription factors.
MCAO was performed MCAO mice were euthanized immediately 60 minutes after surgery. In the MCAO+Recan group, the suture was taken out 60 minutes after the onset of occlusion and mice were allowed to recover for an additional 3 hours before euthanasia. Sham mice were subjected to only anaesthesia and the manipulation of surrounding tissues and arteries.

overall_design: Three experimental groups (n=44), sham (SHAM, n=16), 1-hour MCAO (MCAO, N=17), and 1-hour MCAO with 3-hour recovery post-recanalization (MCAO+Recan, n=11), were included in the dataset. Both young (3-6 months old, n=20) and aged (18-24 months old, n=24) male (n=20) and female (n=24) mice were used.

first: Glen

middle: C

last: Jickling

first: Ian

last: Winship


title: Circadian Reprogramming by Timed Sodium Intake Reveals Transcriptional Pathways of Daily Salt Handling in the Colon.

status: Public on Oct 31 2025

city: Tokyo

first: Kenichiro

last: Kinouchi

address: 35 Shinanomachi, Shinjuku-ku

country: Japan

institute: Keio University School of Medicine

type: Genome binding/occupancy profiling by high throughput sequencing

summary: ChIP-seq was performed to investigate the genome-wide occupancy of the circadian clock and mineralocorticoid receptor in the colon.

overall_design: male C57BL/6 mice were subjected to ad libitum normal chow diet. Chromatin immunoprecipitation with BMAL1 or MR antibody followed by deep sequencing was performed using the colon tissue harvested at ZT12.

first: Takuto

last: Torimitsu

first: Hiroshi

last: Itoh


title: Ribosomal RNA synthesis by RNA polymerase I is regulated by premature termination of transcription.

status: Public on Nov 01 2025

city: Toulouse

first: olivier

last: Gadal

address: 169 av. Marianne Grunberg_Manago

department: UMR5087 CNRSS

country: France

institute: centre de biologie integrative (CBI)

summary: The synthesis of the large rRNA precursors is achieved by the RNA polymerase I (Pol I) enzyme. During elongation, Pol I exhibits a highly discontinuous process with a high rate of pauses. Here, we propose that Pol I Premature Termination of Transcription (PTT) is a major regulatory step limiting rRNA production in vivo. We previously isolated a mutant of Pol I carrying the RPA135-F301S mutation. This mutant (hereafter called SuperPol) is able to produce 1.5-fold more rRNA than wild-type (WT). Combining crosslinking and analysis of cDNAs (CRAC) and rRNA analysis we could show that increased rRNA production in SuperPol is associated with a reduced premature release of nascent transcripts and a shift of the polymerase distribution toward the 3’ end of rDNA genes. In vitro, SuperPol shows a defect in nascent transcript cleavage combined with an increased ability to resume elongation after a pause, to the detriment of transcriptional fidelity. SuperPol is resistant to high concentrations of BMH-21, a drug that severely impairs Pol I elongation and triggers the proteasome-mediated degradation of the largest subunits of Pol I, in both human and yeast. Compared to WT, SuperPol retains subunits stability and maintains high levels of Pol I transcription upon BMH-21 treatment. These results show that PTT is both alleviated in SuperPol and targeted by BMH-21 in WT Pol I.

overall_design: CRAC protocol performed on samples containing HTP-tagged proteins: Rpa135(WT)-HTP, Rpa135(F301S)-HTTP s were analyzed and in presence of BMH-21.

first: Chaïma

last: Azouzi

first: Marion

last: Aguirrebengoa

first: Christophe

last: Dez

first: Olivier


title: Detection and monitoring of translocation renal cell carcinoma via plasma cell-free epigenomic profiling

city: Boston

first: Karl

last: Semaan

state: MA

address: Brookline Ave 450

country: USA

institute: Dana-Farber Cancer Institute

type: Methylation profiling by high throughput sequencing

summary: Translocation renal cell carcinoma (tRCC) is an aggressive fusion-driven subtype of kidney cancer that is frequently misdiagnosed due to morphologic overlap with other kidney cancer subtypes. Conventional liquid biopsy assays targeting DNA alterations are suboptimal for use in tRCC due to its paucity of genomic changes. We demonstrate the utility of cell-free chromatin profiling to noninvasively detect and monitor tRCC with high accuracy, a method that could have applicability to other genomically quiet cancers.

overall_design: Chromatin immunoprecipitation DNA-sequencing (ChIP-seq) for histone modifications H3K27ac, and H3K4me3, methylated immunoprecipitation and high-throughput sequencing (MeDIP-seq), and low pass whole genome sequencing on cell-free DNA. Chromatin immunoprecipitation DNA-sequencing (ChIP-seq) for histone modifications H3K4me3, and methylated immunoprecipitation and high-throughput sequencing (MeDIP-seq) on tRCC cell lines.

first: Simon

last: Garinet

first: Toni

middle: K

last: Choueiri

first: Matthew

middle: L

last: Freedman

first: Sylvan

last: Baca

first: Srinivas

middle: R

last: Viswanathan


title: YTHDF3 Promotes the Translation of m6A-Enriched Mitosis-Associated Genes to Attenuate the Responsiveness to Neoadjuvant Chemotherapy in Esophageal Cancer [RIP-seq]

status: Public on Nov 03 2025

city: zhengzhou

first: Xiangyu

last: Wang

state: Henan

address: No. 100 Science Avenue

country: China

institute: Zhengzhou University School of Basic Medical Sciences

summary: Neoadjuvant chemotherapy (NACT) is a pivotal treatment strategy for esophageal cancer, significantly improving patient prognosis and 5-year survival rates. However, a substantial proportion of patients exhibit resistance to NACT and consequently fail to benefit from it. As NACT responsiveness is influenced by multiple distinct molecular pathways, it is essential to systematically investigate the mechanisms underlying poor therapeutic responses. In this study, we found that YTHDF3 directly enhances the m6A-dependent translation of key mitotic regulators, CDCA8 and INCENP, thereby reducing cellular sensitivity to NACT.

overall_design: To investigate the transcriptome-wide targets of YTHDF3, RNA immunoprecipitation sequencing (RIP-seq) was performed using an anti-YTHDF3 antibody in KYSE30 esophageal cancer cells. This approach enabled the identification of YTHDF3-bound mRNAs under endogenous conditions, providing insights into its regulatory role in post-transcriptional gene expression.

first: Xiang

middle: Y

first: Ting

last: wang

first: Si

middle: M

last: Zhao

first: Zi

middle: G

last: Dong


title: Dynamic neutrophil-keratinocyte communication network centered on IL-36/TNFSF15 responses characterizes inflammatory responses in generalized pustular psoriasis.

status: Public on Oct 29 2025

city: Ann Arbor

first: Poulami

last: Dey

address: 1301 Catherine St

institute: Michigan Medicine

type: Expression profiling by high throughput sequencing

summary: Generalized pustular psoriasis (GPP) is a severe subtype of psoriasis characterized by epidermal neutrophil infiltration, often presenting as acute, potentially life-threatening flares. However, the characterization of the immune micro-environment in GPP lesions remains largely unknown. Here, we used single-cell RNA profiling to interrogate the transcriptomes of 60,000 single cells from GPP lesional skin (n=13) and healthy adult skin (n=4), combined with spatial transcriptomics. We identified a unique neutrophil subset lacking CASP8 expression but exhibiting elevated levels of inflammatory pathway genes, including RIPK1, NFKB1, IL1B, CXCL1, and CXCL8 in GPP flares, illustrating neutrophil transition from pre-inflammatory to a pro-inflammatory state, and activation of a communication network between IL36G+ keratinocytes and neutrophils in GPP lesions, with TNFSF15 (TL1A) released from neutrophils exaggerating the inflammatory crosstalk. We further demonstrated that fibroblasts and capillary endothelial cells function as central communication hubs in GPP, through dynamic receptor-ligand interactions with several spatially proximate immune cells, including T cells, neutrophils, and macrophages. In this work, we provide an in-depth view of immune cell participation and highlight the role of neutrophil-keratinocyte crosstalk in GPP pathogenesis.

overall_design: To investigate changes in cell type composition and transcriptional profiles in lesional skin from GPP patients, compared with skin from healthy controls.

first: Johann

middle: E

last: Gudjonsson

first: Lam

last: Tsoi


title: DNGR-1 signalling limits dendritic cell activation for optimal antigen cross-presentation

status: Public on Oct 28 2025

city: London

first: Probir

last: Chakravarty

address: 1 Midland Road

country: United Kingdom

institute: Francis Crick Institute

summary: Innate immune receptors often induce activation of conventional dendritic cells (cDCs) and enhance antigen (cross-)presentation, favouring immune responses. DNGR-1 (CLEC9A), a receptor expressed by type 1 cDCs (cDC1s) and implicated in immune responses to viruses and cancer, recognises F-actin exposed on dead cell remnants and promotes cross-presentation of associated antigens. Here, we show that recruitment of phosphatase SHIP1, a process governed by a single amino acid residue adjacent to the signalling motif of the receptor, partly explains how DNGR-1 fails to trigger cDC1 activation in vitro. Substituting this residue converts DNGR-1 into an activating receptor but decreases induction of cross-presentation of dead cell-associated antigens. Introducing the reverse mutation into the related receptor Dectin-1 impairs its activation capacity while enhancing its ability to promote cross-presentation. These findings reveal a functional trade-off in receptor signalling and suggest that DNGR-1 has evolved to prioritise antigen cross-presentation over cellular activation, possibly to minimise inflammatory responses to dead cells.

overall_design: DNGR-1 or mutant DNGR-1 expressing MuTuDCs were treated with 12.5 nM DNGR-1 ligand for 6 hours

first: Michael

last: Buck

first: Caetano

last: ReiseSousa


title: Protein Kinase Cι dictates tumor trajectory, cell state plasticity and immune surveillance in lung adenocarcinoma

city: Rochester

first: Cheng

last: Zhang

state: MN

address: 200 1st street SW

institute: Mayo Clinic

summary: By genetically ablating oncogenic PKCι in a Kras/Trp53-driven lung adenocarcinoma mouse model, we identify two distinct tumor trajectories that resemble lung development and lung regeneration, respectively. Mechanistically, loss of PKCι expression leads to the accumulation of senescent tumor cells with transcriptional similarities to the pre-AT1 transitional cell state (PATS) observed during alveolar regeneration after injury. In addition to inhibiting cellular plasticity through stable proliferation arrest, senescent PATS-like tumor cells induce formation of large, organized aggregates of immune cells called tertiary lymphoid structures (TLS) within KPI tumors.

overall_design: Individual tumors were microdissected from ~30-week KP (KrasG12D/Trp53fl/fl) and ~40-week KPI (KrasG12D/Trp53fl/fl/Prkcifl/fl) animals (n = 5 tumors/animal; 2 animals/genotype). After removal of endothelial cells, red blood cells, and dead cells, scRNA-seq was performed on tumor samples containing both cancer and immune cells.

first: Duy

middle: T

last: Nguyen

first: Luis

middle: I

last: Prieto

first: Hu

last: Li

first: Darren

middle: J

last: Baker

first: Alan

middle: P

last: Fields


title: Clinical, physiologic, imaging, and molecular responses to cannabis smoking: the Canadian Users of Cannabis Smoke (CANUCK) Study

city: Vancouver

first: Janice

last: Leung

state: BC

address: Room 166, 1081 Burrard Street

country: Canada

institute: Centre for Heart Lung Innovation, St. Paul’s Hospital, University of British Columbia

summary: Background. The growing popularity of cannabis smoking in an era of legalization has prompted concerns about respiratory health. Objective. To investigate clinical and airway epithelial transcriptomic features associated with cannabis smoking.  Methods. This cross-sectional study analyzed 139 cannabis-smoking participants categorized by joint-year exposure (low: ≤5; moderate: >5-20; high: >20), and 57 never-smokers. We evaluated respiratory symptom questionnaire scores, lung function measurements, and chest computed tomography and hyperpolarized 129Xe pulmonary magnetic resonance imaging measurements across groups. We compared the expression of immune response signatures and mucin genes in airway epithelial brushings collected from bronchoscopy. Using air-liquid interface (ALI) cell cultures, we quantified epithelial MUC5AC protein and correlated its expression with clinical outcomes. Results. Among cannabis-smoking individuals (48% male and median age of 27 years), 84% reported current or former cigarette smoking or vaping. Cannabis-smoking groups reported worse respiratory symptoms than never-smokers. High joint-year cannabis-smoking participants showed lower pre-bronchodilator FEV1/FVC and FEF25-75, more radiographic emphysema, and more ventilation abnormalities than never-smokers. Airway epithelial brushings from cannabis-smoking individuals demonstrated increased type 2 immune response, decreased type 17 immune response, and higher MUC5AC gene expression than non-cannabis-smoking individuals. Epithelial MUC5AC protein expression in cell cultures correlated with worse clinical outcomes and imaging abnormalities. Conclusions. Cannabis smoking, particularly at high exposures, is associated with worse respiratory symptoms, lower lung function, functional imaging abnormalities, and dysregulated immune responses in the airway epithelium. These observations suggest respiratory harm associated with cannabis smoking and underscore the concerns for future respiratory morbidities related to persistent cannabis use.

overall_design: RNA-seq profiling of airway epithelial samples from cannabis-smoking and non-cannabis individuals.

first: Don

middle: D

last: Sin


title: Deletion of Ptpn2 in B cells contributes to development of autoimmunity

status: Public on Oct 27 2025

city: Aurora

first: Kristen

last: Wells

state: CO

address: 1775 Aurora Ct,

department: Barbara Davis Center

institute: University of Colorado Anschutz

summary: Autoimmunity arises when self-reactive B and T cells target the body’s own tissues, with B cells contributing through antigen presentation to T cells and production of autoantibodies and pro-inflammatory cytokines. Genome wide association studies (GWAS) have suggested that single nucleotide polymorphisms (SNPs) in protein tyrosine phosphatase non-receptor type 2 (PTPN2), which is ubiquitously expressed throughout the body, are associated with development of autoimmune diseases, such as rheumatoid arthritis (RA), Crohn’s disease, and type 1 diabetes (T1D). While prior studies have focused on the role of Ptpn2 in T cells and other cell types, its function in B cells remains unknown. To test the B cell-intrinsic role of Ptpn2, we generated a B cell-specific deletion of Ptpn2 in mice (Mb1-Cre;Ptpn2fl/fl). We found that loss of Ptpn2 in B cells promotes organ inflammation, increases the frequency of autoimmune-associated B cells (ABCs) and plasmablasts in the periphery, and increases autoantibody levels in the serum. Moreover, we found that Ptpn2 acts as a negative regulator of the JAK/STAT and TLR7 pathways in B cells. In line with this, treatment of B cells from Mb1-Cre;PTPN2fl/fl mice with IFNy and TLR7 agonist leads to enhanced differentiation into ABCs. These findings highlight the critical role of Ptpn2 in B cell function and its potential as a key regulator in preventing B cell associated autoimmunity.

overall_design: B cells were isolated from spleen from 5 control and 6 PTPN2 B cell knock out mice.

first: Bridget

last: Alexander

first: Soojin

last: Kim

first: Kevin

last: Toole

first: Maya

last: Hundter

first: Scott

last: Wemlinger

first: Daniel

last: Regan

first: Andrew

last: Getahun

first: Mia

last: Smith


title: Digital transformation of herbal medicine: Conversion to biological entity data using digestive herbal medicine-induced transcriptome sequencing_second_A549

city: Daejeon

first: Musun

last: Park

address: 1672 Yuseong-daero, Yuseong-gu

country: South Korea

institute: Korean Institute of Oriental Medicine

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

overall_design: Refer to individual Series


title: Deletion of KLHDC3, an E3 ubiquitin ligase complex substrate receptor, leads to obesity in mice

status: Public on Oct 22 2025

city: Meblourne

first: Alistair

middle: Morgan

last: Chalk

state: VIC

address: 1G Royal Parade

department: Bioinformatics

country: Australia

institute: WEHI

summary: Protein ubiquitination is a critical post-translational modification that regulates protein stability and cellular homeostasis. KLHDC3 is a substrate recognition receptor within the recently identified C-terminal degron-mediated DesCEND ubiquitination pathway. It has been characterised to selectively bind proteins with C-terminal RxxxG motifs, targeting them for degradation. Unlike the well-characterised N-terminal degron pathway, the physiological roles of C-terminal degrons remain poorly understood. To investigate KLHDC3 function in vivo, we generated Klhdc3-deficient (Klhdc3-/-) mice. These mice exhibited sub-Mendelian birth rates and progressive postnatal lethality, with a median survival of 136 days and maximum survival observed of ∼1 year of age. Early growth retardation was apparent, followed by a normalisation of body mass with age. However, as Klhdc3-/- mice aged they developed pronounced obesity at the expense of lean mass, with some individuals reaching fat mass exceeding 50% of total body weight. Combined transcriptomic and proteomic analyses of Klhdc3-/- embryonic fibroblasts revealed significant changes in protein expression with minimal impact on transcript levels, consistent with KLHDC3’s role in post-translational regulation. Among the upregulated proteins, HINT1 was identified as a novel KLHDC3 substrate, possessing a C-terminal degron motif. Protein stability assays and immunoblotting confirmed HINT1 as a direct target of KLHDC3. These findings establish a new in vivo physiological role for the DesCEND pathway and highlight KLHDC3 as a key regulator of development, survival, and adiposity in mice.

overall_design: 3'RNA-seq (methods used BRB-seq)

first: P

middle: A

last: Buco

first: M

middle: F

last: Smeets

first: Z

last: Liang

first: A

first: S

last: Taylor

last: Gupte

first: J

last: Heraud-Farlow

first: C

last: Walkley


title: Digital transformation of herbal medicine: Conversion to biological entity data using digestive herbal medicine-induced transcriptome sequencing_second_HepG2


title: Piezo1 balances the osteogenic-tenogenic plasticity of periosteal progenitor cells through the YAP pathway

city: ShangHai

first: Lijun

last: Wang

state: China

address: 320 Yueyang Road

department: Institute of Biochemistry and Cell Biology

institute: Chinese Academy of Sciences

summary: The extremity tendons and bones are derived from limb bud mesenchyme, which eventually become cells of different tissues. Despite their common origin, it was widely believed that tenocytes and skeletal cells are distinct lineages without interconversion. However, we found that periosteal skeletal progenitor cells could transform between osteogenic and tenogenic commitment. SCX can label the periosteal progenitor cell population. Loss of Piezo1 arrests the periosteal progenitor cells in a progenitor state. Piezo1 deficiency leads to upregulation of Scx expression due to the inhibited YAP nuclear localization. Loss of Piezo1 showed increased tenogenic marker genes and decreased osteogenic marker genes. The periosteal progenitor cells can regenerate the injured tendon more robustly when Piezo1 is absent. Taken together, our data reveal that periosteal SCX+ progenitor cells compromise the osteogenic ability and acquire the tenocyte-biased lineage commitment after loss of Piezo1, providing a strategy to modulate the periosteal progenitor cells for tissue regeneration.

overall_design: Periosteal cells were extracted from femurs and tibias of Prx1 Cre; Ai9/+ and Prx1 Cre; Ai9/+; Piezo1 fl/fl mice at 8 week.

first: Weiguo

last: Zou

first: Qian

last: Ren

first: Shuqin

last: Chen

first: Lixiang

last: Lou

first: Wenhui

last: Xing

first: Jun

last: Sun

first: Xuye

last: Hu

first: Miaomiao

first: Heng

last: Feng

first: Matthew

middle: B

last: Greenblatt


title: Cathepsin D-Mediated MHC-I Degradation Contributes to Immune Evasion in Microsatellite Stable Colorectal Cancer

status: Public on Oct 18 2025

city: Guangzhou

first: Weixiang

last: Zhan

state: Guangdong

address: 广东省广州市天河区员村二横路东璟花园

institute: Sun Yat-sen university

summary: Microsatellite stable (MSS) colorectal cancer (CRC) is often characterized as a "cold" tumor, exhibiting minimal responsiveness to monotherapy with PD-1 antibodies. The underlying mechanisms of this intrinsic unresponsiveness to immunotherapy have been elusive. Here, we report that cathepsin D (CTSD) is highly expressed in MSS CRC, significantly contributing to its resistance to immunotherapy. Specifically, CTSD facilitates immune evasion by shielding cancer cells from cytotoxic T-cell-mediated killing. Mechanistically, as a protease, CTSD interacts with the α2 domain of the major histocompatibility complex class I (MHC-I) molecule via its catalytic domain's light chain, promoting the degradation of MHC-I through lysosomal pathways and disrupting the recycling of MHC-I to the cell surface. Notably, deletion or pharmacological inhibition of CTSD with pepstatin A prevents this immune evasion and enhances the efficacy of anti-PD-1 antibodies. Collectively, these findings highlight the role of CTSD in immune evasion and provide a compelling rationale for the development of a novel combination therapy involving CTSD inhibition and anti-PD-1 immunotherapy in CRC.

overall_design: To investigate the functional role of CTSD in CRC, NC and CTSD knockdown CT26 tumors. To elucidate the impact of CTSD depletion on the immune microenvironment of MSS CRC, we conducted single-cell RNA sequencing (scRNA-seq) to profile transcriptomic alterations in shCTSD versus shNC CT26 syngeneic tumors. After stringent quality control, we obtained 68,159 high-quality single-cell transcriptomes from both tumor groups

first: Yang

last: Fu

first: Yina

last: Liu

first: Runkai

last: Cai

first: Fan

last: Bai

first: Chenxu

last: Guo

first: Yi

last: Cheng

first: Zehua

last: Wu

first: Ge

last: Qin

first: Yuqian

last: Xie

first: Jianwei

last: Zhang

first: Yanhong

last: Deng


title: RNA Sequencing of Liver and Skeletal Muscle from WT and Heterozygous IGF-1R Mutant Mice

status: Public on Oct 20 2025

first: Alexander

last: Tyshkovskiy

state: Massachusetts

address: 77 Avenue Louis Pasteur

institute: Brigham & Women's Hospital, Harvard Medical School

summary: This dataset includes gene expression profiles from liver and skeletal muscle samples of young female and male C57BL/6J mice with heterozygous IGF-1R R1096C mutation, along with age-matched wild-type controls.

overall_design: Young (4-month-old) female and male wildtype (WT) and heterozygous IGF-1R R1096C (IGF-1R Het) C57BL/6J mice. 48 biological replicates: 5-6 liver and 5-7 skeletal (gastrocnemius) muscle samples per genotype and sex.

first: Ulalume

last: Hernández-Arciga

first: Alibek

last: Moldakozhayev

first: Vadim

middle: N

last: Gladyshev

first: Andrey

last: Parkhitko


title: Differential gene expression analysis between miR-17 overexpressing and control human chondrocytes

status: Public on Oct 16 2025

city: Nanchang

first: Jinghong

last: Yuan

state: Jiangxi

address: No.1 Minde Road

institute: The Secondly Affiliated Hospital of Nanchang University

summary: Identify the differentially expressed genes in chondrocytes overexpressing miR-17 compared to controls, and predict the biological functions and potential regulatory signaling pathways of miR-17 through functional enrichment analysis.

overall_design: Total RNA was extracted from three miR-17 overexpressing chondrocyte samples and three normal control chondrocytes, quantified using a NanoDrop ND-2000 (Thermo Scientific), and RNA integrity was assessed using an Agilent Bioanalyzer 2100 (Agilent Technologies). After the RNA passed quality control, labeling, hybridization, and washing of the microarray followed the standard procedure. First, the total RNA was reverse-transcribed into double-stranded cDNA, which was then used to synthesize cRNA labeled with Cyanine-3-CTP (Cy3). The labeled cRNA was hybridized to the microarray, washed, and scanned using an Agilent Scanner G2505C (Agilent Technologies) to obtain the raw images.

first: Yameng

last: Wang

first: Jingyu

last: Jia


title: Surface mechanics and compressive stress impact mammalian follicle development

status: Public on Oct 15 2025

city: Singapore

first: Chii Jou

last: Chan

address: 5A Engineering Drive 1

department: Mechanobiology Institute

country: Singapore

institute: National University of Singapore

summary: The maturation of functional eggs in ovaries is essential for successful reproduction in mammals. Despite its biological and clinical importance, the underlying mechanisms regulating folliculogenesis remain enigmatic. Here, using murine ovaries, we report that the theca cells surrounding secondary follicles play a critical role in regulating follicle development through mechanical signalling. Using biophysical approaches, we found that the contractile theca cells exert significant compressive stress to the follicular interior through active assembly of fibronectin. Manipulation of compressive stress by targeting theca cell contractility, basement membrane integrity or intrafollicular pressure leads to changes in follicle size and mechanics, granulosa cell YAP signalling and oocyte-granulosa cell communications. Transcriptomics and quantitative immunofluorescence reveal that compressive stress impacts functional follicle growth through regulating the balance between granulosa cell proliferation and death that drives tissue pressure homeostasis. Altogether, our study identifies new mechanical functions of theca cells and provides quantitative evidence of the role of compressive stress in regulating mammalian folliculogenesis.

overall_design: RNA sequencing of granulosa cells and oocytes isolated from encapsulated follicles grown for three days in control, Blebbistatin treatment, and dextran treatment.

first: Arikta

last: Biswas

first: Kosei

last: Tomida


title: Maresin 1 Modulates Cardiac and Renal Lipid Profiles in Hypertensive Rats

status: Public on Oct 24 2025

city: Tampa

first: Olha

last: Kravtsova

state: Florida

address: 560 Channelside Dr

institute: University of South Florida

summary: BACKGROUND: Chronic inflammation contributes significantly to hypertension and associated target organ damage, particularly in the heart and kidneys. Specialized pro-resolving mediators (SPMs), a class of bioactive lipids primarily derived from omega-3 fatty acids, play key roles in resolving inflammation and maintaining tissue homeostasis. Among them, Maresin 1 (MaR1) has been implicated in cardiovascular regulation and blood pressure control. We hypothesized that MaR1 may mitigate salt-induced hypertension and its related effects in Dahl salt-sensitive (SS) rats. This study evaluated the impact of MaR1 on blood pressure progression, cardiac function, fibrosis, lipid metabolism, gene expression, and circadian rhythms in SS rats fed a high-salt diet. METHODS: SS rats were fed a high-salt diet and treated with MaR1. Mean arterial pressure (MAP) and heart rate (HR) were continuously monitored. Echocardiography and histology were used to assess cardiac structure, contractility, and fibrosis. Lipidomic profiling quantified inflammation-resolving lipid mediators, and transcriptomic analysis identified organ-specific gene expression changes. RESULTS: MaR1 treatment did not significantly alter MAP, HR, or cardiac structure and function. Echocardiographic and histological evaluations showed no significant changes in cardiac remodeling, contractility, or collagen deposition in the heart or kidney. However, lipidomic profiling revealed shifts in inflammatory lipid mediators, suggesting immunomodulatory and metabolic effects of MaR1. Transcriptomic analysis demonstrated organ-specific gene expression changes, with upregulation of circadian and metabolic pathways in the heart and modulation of immune signaling in the kidney. Notably, MaR1 influenced circadian blood pressure rhythms, enhancing amplitude and shifting the acrophase, consistent with altered expression of circadian clock genes. CONCLUSIONS: Although MaR1 did not affect hypertension development directly, its modulation of lipid metabolism, inflammatory pathways, and circadian regulation suggests therapeutic potential. Future studies should explore extended treatment durations and combination strategies to fully evaluate its role in cardiovascular and renal disease management.

overall_design: Male animals were used for the study.  At 8 weeks of age animals were implanted with a telemeter to measure chronic blood pressure. After a few days of recovery animals were switched to high salt (HS, 4% NaCl) diet for 3 weeks. Maresin 1 (MaR1, No. 1268720-28-0, Cayman Chemical Company) was administered subcutaneously via an implanted osmotic minipump (2ML4, ALZET Osmotic Pump) to deliver either the vehicle control or Maresin 1 at a dosage of up to 1.3 µg/kg/day continuously over 3 weeks HS challenge. After 3 weeks on HS, animals were anesthetized with isoflurane and kidneys were collected. Kidney cortex from one kidney and left ventricle of heart  were snap-frozen and used for transcriptomic analysis to compare gene expression in vehicle and MaR1-treated groups.

last: Staruschenko


title: An IL-17-Ly6G+Polymorphonuclear Neutrophil (PMN) axis limits protective host responses against tuberculosis.

city: New Delhi

first: DHIRAJ

last: KUMAR

state: Delhi

address: ARUNA  ASAF ALI MARG

department: Cellular Immunology

country: India

institute: ICGEB, New Delhi

summary: The protective correlates of Mycobacterium tuberculosis (Mtb) infection-elicited host immune responses are incompletely understood. Here we report pro-pathogenic crosstalk between IL-17, COX2, and Ly6G+Polymorphonuclear Neutrophils (PMNs). We show that most intracellular bacilli in the wild-type (WT) mice's lungs are Ly6G+PMN-resident. In BCG-vaccinated WT mice, Mtb continues to persist inside Ly6G+PMNs, which is sensitive to COX2 inhibition. Using a genetically susceptible IFNγ -/- mice model, we report that excessive neutrophil infiltration and corresponding bacteremia are dependent on Ly6G+PMN-derived IL-17. COX2 inhibition and IL-17 neutralization reverses Ly6G+PMN infiltration, associated pathology and death in IFNγ -/- mice. Inhibiting RORγT along with COX2 in Mtb-infected WT mice further demonstrates the pathological nature of the IL-17- Ly6G+PMN axis. Clinically, in a prospective cohort of pulmonary TB subjects, high neutrophil count and serum IL-17 levels precipitate adverse treatment outcomes. Therefore, targeting the pro-pathogenic IL-17- Ly6G+PMN axis could enhance TB prevention and therapy in normal and genetically vulnerable subjects.

overall_design: Comparative gene expression profiling analysis of RNA-seq data from Polymorphonuclear Neutrophils of Mycobacterium tuberculosis infected mice treated with BCG and/or Celecoxib and uninfected mice

first: Priya

last: Sharma

first: Mrinmoy

last: Das

first: Dhiraj

last: Kumar

first: Amit

last: Singhal


title: Respiratory syncytial virus nonstructural protein 1 inhibits secretion of cytokines and chemokines by differentiated primary nasal epithelial cells cultured at air-liquid interface

city: Bilthoven

first: Amadeo

last: Muñoz

address: Antonie van Leeuwenhoeklaan 9

country: Netherlands

institute: RIVM

summary: Respiratory syncytial virus (RSV) is a major cause of severe respiratory infections in children and older adults. Several vaccines have recently been approved, which are all based on the RSV fusion (F) protein. Among the strategies to induce a broader immune response is the development of live-attenuated RSV vaccines, for example by disabling nonstructural protein 1 (NS1). RSV NS1 has been found to modulate the host immune response by repression of interferon (IFN) production. However, functional characterization of this protein was mainly performed in immortalized cell lines, which do not necessarily represent the in vivo situation.    Here, we assessed the effect of NS1 mutations on replication and host responses in differentiated primary human nasal epithelial cells (HNEC) cultured at air-liquid interface (ALI), which mimic several physiological properties of the human airways. Using a newly developed yeast-based RSV reverse genetics system, inactivating mutations in the NS1 gene were introduced. These mutations did not affect viral replication in Vero and A549 cells. However, in HNEC we observed a delayed replication of the NS1 mutants compared to the WT virus. Bulk RNA sequencing data from early post infection revealed a stronger antiviral signature in HNEC that were infected with NS1 mutants compared to WT, characterized by upregulation of IFN-β and IFN-λ1/2/3 and chemokines CXCL11 and CCL5. This signature was confirmed by analysis of the cytokines that were released into the HNEC basal medium. Finally, the basal medium containing these cytokines was used for an indirect immune cell migration assay. In this set-up, both WT and NS1 mutant viruses induce migration of mainly neutrophils.  In conclusion, this study shows that RSV NS1 supports viral replication not only via inhibition of the production of IFNs, but also by reducing early chemokine production and secretion by epithelial cells. Furthermore, our data highlight the suitability of the ALI transwell model for preclinical assessment of live-attenuated vaccine candidates.

overall_design: Cell source: well-differentiated primary nasal epithelial cells, cultured at Air-liquid interface 3 different nasal donors were used. Two transwells per condition were infected with the following RSV strains: RSV-X WT (wild-type virus) RSV-X NS1Y125A (Y125A point mutation in the NS1 protein) RSV-X NS1L132A/L133A (L132A/L133A point mutations in the NS1 protein) Mock: no virus Whole cell lysates were made at 20 hours post infection.  RNA was isolated from the cell lysates to perform RNA-seq profiling.

first: Rosanne

middle: W

last: Koutstaal

last: Munoz Garcia

first: Nadine

last: Ebert

first: Manon

last: Licheri

first: Anke

last: Lakerveld

first: Hendrik-Jan

last: Hamstra

first: Anne

last: Gelderloos

first: Jørgen

last: de Jonge

first: Cécile

last: van Els

first: Ronald

last: Dijkman

first: Volker

last: Thiel

first: Puck

last: van Kasteren


title: Digital transformation of herbal medicine: Conversion to biological entity data using digestive herbal medicine-induced transcriptome sequencing_second_HT29

first: Musun

last: Park


title: PCBP1 binding to single-stranded poly-cytosine motifs enhances cGAS sensing and impairs breast cancer development [snRNA-Seq]

city: Charleston

last: Fréreux

state: SC

address: 173 Ashley Avenue

institute: Medical University of South Carolina

summary: The cGAS-STING pathway plays a central role in controlling tumor progression through nucleic acid sensing and type I Interferon production. Here, we identify Poly(rC) Binding Protein 1 (PCBP1) as a tumor suppressor that amplifies cGAS-STING signaling in breast cancer. Using patient datasets and a transgenic mouse model with conditional PCBP1 knockout in mammary epithelial cells, we show that PCBP1 expression correlates with improved survival, reduced tumor burden, increased type I IFN and ISG expression, and elevated cytotoxic T cell infiltration. Mechanistically, PCBP1 binds cytosine-rich single-stranded motifs via its KH domains and increases cGAS affinity to these nucleic acids. Disruption of the conserved GXXG motif impairs PCBP1's nucleic acid binding and cGAS activation. Although cGAS is a double-stranded DNA sensor with no intrinsic sequence specificity, we uncover that the single-stranded nucleic-acid binding protein PCBP1 enhances cGAS sensing by engaging sequence-specific motifs, acting as an important nucleic acid co-sensor that impairs tumorigenesis.

overall_design:
We used sized-matched mammary tumors (~100mg) from a C57BL/6 transgenic mouse model expressing the MMTV-PyMT (polyomavirus middle T antigen) oncogene, which drives mammary tumorigenesis, in addition to a MMTV-Cre PCBP1(fl/fl) system that selectively knocks out PCBP1 in mammary epithelial cells. These mice, abbreviated as PyMT PCBP1–/–, were compared to control animals expressing the MMTV-PyMT and MMTV-Cre constructs along with the non-floxed PCBP1(wt/wt) alleles, referred to as PyMT PCBP1+/+. The mammary tumors were dissociated, the nuclei sorted by flow cytometry and analyzed by single-nuclei RNA-sequencing.
Please note that the same mouse model associated with GSE307616 RNA-seq dataset was used for the current study

first: Joseph

last: Karam

first: Breege

middle: V

last: Howley

first: Bryan

last: Granger

first: Paramita

last: Chakraborty

first: Annamarie

middle: C

last: Dalton

first: Bidyut

middle: K

last: Mohanty

first: Silvia

last: Vaena

first: Romeo

last: Martin

first: Shikhar

last: Mehrotra

first: Philip

middle: H

last: Howe


title: PCBP1 binding to single-stranded poly-cytosine motifs enhances cGAS sensing and impairs breast cancer development

overall_design: We used mammary tumors from a C57BL/6 transgenic mouse model expressing the MMTV-PyMT (polyomavirus middle T antigen) oncogene, which drives mammary tumorigenesis, in addition to a MMTV-Cre PCBP1(fl/fl) system that selectively knocks out PCBP1 in mammary epithelial cells. These mice, abbreviated as PyMT PCBP1–/–, were compared to control animals expressing the MMTV-PyMT and MMTV-Cre constructs along with the non-floxed PCBP1(wt/wt) alleles, referred to as PyMT PCBP1+/+. RNA was prepared from the mammary tumors and RNA-sequencing performed.


title: Long-term remissions and marked decreases in resident memory T cells following high induction dosing with risankizumab in randomized patients with moderate-to-severe plaque psoriasis

status: Public on Oct 17 2025

first: Poulami

last: Dey

summary: The phase 2 KNOCKOUT (NCT05283135) study evaluated higher-than-approved doses of risankizumab, an interleukin-23 inhibitor, for treatment of moderate-to-severe plaque psoriasis. Patients received either 300 or 600 mg of risankizumab at Weeks 0, 4, and 16 and were monitored through Week 100 without further dosing. Efficacy and safety were tracked throughout the study and RNASeq was performed on lesional/non-lesional tissue. Nine patients per treatment group completed dosing. At Weeks 28 and 52, Psoriasis Areas and Severity Index 75/90/100 responses were achieved by 94.4%/94.4%/83.3% and 77.8%/61.1%/44.4% of all patients, respectively, with no new safety signals. At Week 52, TRM cell numbers in lesional skin were markedly reduced, with numbers similar to non-lesional resident memory T cell numbers at Week 0. High skin clearance rates with higher-than-approved initial dosing of risankizumab with prolonged maintenance of skin clearance, despite the lack of continuous dosing, represent a potential novel treatment strategy for patients with psoriasis.

overall_design:
To investigate changes in cell type composition and transcriptional profiles in psoriatic skin from patients with psoriasis after high-dose risankizumab treatment (at week 52), compared with paired baseline lesional samples collected at week 0.

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

first: Johann

last: Gudjonsson

first: Lam

last: Tsoi


title: Systematic Pan-cancer Functional Inference and Validation of Hyper, Hypo and Neomorphic Mutations

status: Public on Oct 21 2025

city: New York

first: Somnath

last: Tagore

state: NY

address: 650W, 168th Street

institute: Columbia University

summary: While the functional effects of many recurrent cancer mutations have been characterized, the TCGA repository comprises more than 10M non-recurrent events, whose function is unknown. We propose that the context specific activity of transcription factor (TF) proteins—as measured by expression of their transcriptional targets—provides a sensitive and accurate reporter assay to assess the functional role of oncoprotein mutations. Analysis of differentially active TFs in samples harboring mutations of unknown significance—compared to established gain (GOF/hypermorph) or loss (LOF/hypomorph) of function—helped functionally characterize 577,866 individual mutational events across TCGA cohorts, including identification of mutations that are either neomorphic (gain of novel function) or phenocopy other mutations (mutational mimicry). We performed RNA-seq profiles were generated by Pooled Library Amplification for Transcriptome Expression (PLATE-Seq), a highly controlled microfluidic assays for 37 breast cancer-specific PIK3CA mutations in MCF10A cell line. Validation using mutation knock-in assays confirmed 15 out of 15 predicted gain and loss of function mutations and 15 of 20 predicted neomorphic mutations.  This could help determine targeted therapy in patients with mutations of unknown significance in established oncoproteins.

overall_design:
To prospectively validate our functional inference for PIK3CA mutational status, we selected 37 breast cancer specificPIK3CAmutations, comprising 9 GOF, 5 LOF, and 20 NEO predicted events, whose functional relevance had not been previously assessed in the FASMIC repository. For this purpose, differential gene expression signatures were generated from MCF10 cell, following lentivirus-mediated knock-in of mutant PIK3CA cDNA vs. mock cDNA as negative control. RNA-seq profiles were generated by Pooled Library Amplification for Transcriptome Expression (PLATE-Seq), a highly controlled microfluidic assay described in Bush et al., 2017 (PMID: 28740083), for 37 breast cancer-specific PIK3CA mutations in MCF10A cell line.
*** Submitter declares that raw files will be deposited in dbGAP. ***

first: Samuel

last: Tsang

first: Gordon

last: B Mills

first: Andrea

last: Califano


title: Differentially manufactured Arnica montana L. extracts mediate anti-inflammatory effects on human T cells via different signaling pathways

city: Heidelberg

first: Yvonne

last: Samstag

address: INF 305

department: Institute of Immunology

country: Germany

institute: Heidelberg University Hospital

summary: In this study, differentially prepared Arnica extracts and the lead compounds Thymol and Helenalin were directly compared for their immunomodulatory potential using primary human T cells. Extracts from different plant parts (root or whole plant) and prepared by different manufacturing processes inhibited T cell activation and proliferation. nCounter gene expression analysis and subsequent gene set enrichment analysis showed that Arnica preparations intervene in T cell receptor (TCR) signaling. Interestingly, the three tested extracts were, however, found to mediate their effects via interfering with different TCR signaling pathways. The hydroethanolic root extract selectively inhibited the binding of NFκB to DNA, while the aqueous fermented whole plant extract preferentially inhibited NFAT-dependent gene expression. The hydroethanolic whole plant extract (by trend) diminished both, NFκB DNA-binding and NFAT-dependent gene expression.

overall_design: Using the nCounter Human Immunology V2 Panel covering 579 immune-related genes, gene expression in PBTs treated with different Arnica extracts was compared to the respective solvent control sample (H2O or EtOH, respectively). 5 healthy donors were taken for each condition, treated or untreated.

first: Verena

last: Beier


title: Carnosic acid in topical rosemary extract promotes TRPA1-mediated scarless wound healing

city: philadelphia

first: Emmanuel

last: Rapp Reyes

address: 421 curie boulevard brb 1039

institute: University of Pennsylvania

summary: Mammalian skin wounds typically heal with a scar, characterized by fibrotic tissue that disrupts original tissue architecture and function. Therapies to reduce fibrosis and scar formation remain a large unmet clinical need. Rosemary extract, particularly in the form of topical oils and creams, has gained massive popularity within the general public as a potential treatment to reduce scar formation. However, its efficacy and potential mechanism of action remain unknown. We show in adult wound healing mouse models that an ethanol-based rosemary extract reduces fibrosis and promotes scarless wound healing. More specifically, carnosic acid within rosemary leaves acts as an active ingredient and stimulates the TRPA1 nociceptor on cutaneous sensory neurons to promote scarless wound healing. Mice lacking TRPA1 on sensory neurons do not exhibit rosemary-induced tissue regeneration. Taken together, topical rosemary extract may be an effective and cost-efficient therapeutic to reduce scar formation in skin wounds.

overall_design: Inured ears of WT mice treated with control cream or rosemary cream collected at day 7 post injury

last: Rapp

first: Thomas

last: Leung


title: Impact of Sirt2 deficiency on downstream TCR signaling in mouse melanoma tumor-infiltrating T lymphocytes

first: Dongliang

last: Du

address: 111 Magnolia

institute: Moffitt

summary: The T-cell receptor (TCR) signaling pathway is a highly regulated system designed to prevent autoimmunity while ensuring effective immune responses. This regulation is typically mediated through phosphorylation, dephosphorylation, and ubiquitination. Sirt2, is a cytoplasmic NAD+-dependent histone deacetylase with anti-aging and antioxidant properties. Here we reveal acetylation modulated by Sirt2 as a previously unrecognized process controlling TCR signaling. In our study, we found that the loss of Sirt2 in T cells leads to enhanced TCR signaling following T cell activation. Furthermore, we demonstrated that inhibiting Sirt2 in both murine and human tumor-infiltrating lymphocytes restores TCR responsiveness and enhances their anti-tumor activity. This suggests Sirt2 targeting as a potential therapeutic approach for reactivating exhausted T cells within the tumor microenvironment.

overall_design: To investigate the impact of Sirt2 deficiency on pathways downstream of T-cell receptor (TCR) signaling within the tumor microenvironment, we conducted RNA sequencing analysis on tumor-infiltrating T lymphocytes from wild-type and Sirt2 knockout mice bearing B16F10 subcutaneous tumors.

first: Imene

last: Hamaidi

first: Pingyan

last: Cheng

first: Min-Hsuan

last: Wang

first: Alak

last: Manna

first: Min

middle: G

last: Zhang

first: Odesha

middle: O

last: Taylor

first: Bin

last: Fang

first: Bradford

last: Perez

first: Ben

last: Creelan

first: Andriy

last: Marusyk

first: Dongjun

last: Shin

first: Tae-Hyun

last: Hwang

first: Anders

last: Berglund

first: Virginia

middle: S

last: Shapiro

first: Haitao

middle: M

last: Ji

first: Sungjune

last: Kim


title: Gene expression profile at single cell level of human melanoma cell lines, normal human melanocytes and human nevus cells.

status: Public on Oct 12 2025

city: Salt Lake City

first: Robert

middle: L

last: Judson-Torres

state: Utah

address: 2000 Circle of Hope

department: Dermatology

institute: Huntsman Cancer Institute at the University of Utah

summary: Melanomas are considered highly heterogenous in transcriptional state. We used single cell RNA sequencing (scRNA-seq) to analyze the diversity of melanoma cells as compared to primary melanocytes and nevus melanocytes. Sample 1 contain KIT postitive melanocytes sequenced directly ex vivo from human nevi. Sample 2 contains different human melanoma cell lines and primary human melanocytes grown in vitro.

overall_design: Melanoma cell lines were grown in RPMI media supplemented with 10% FBS. NHMs were grown in 254 media supplemented with HGMS. Nevus cells were obtained by excising nevi and sorting for KIT positive cells using the protocol in PMID: 34475532


title: On the origin of the mammalian piRNA pathway

status: Public on Oct 06 2025

city: Haining

first: Xinyu

last: Xiang

state: Zhejiang

address: 718 East Haizhou Road

institute: Zhejiang University

type: Non-coding RNA profiling by high throughput sequencing

summary: The piRNA pathway protects animal germlines form active transposons. Mammals employ a cytoplasmic pathway to post-transcriptionally destroy transposon transcripts and a nuclear pathway that mediates DNA methylation to epigenetically silence transposon expression. When the modern version of these pathways evolved remains unknown. We found that the mammalian version of the cytoplasmic pathway evolved in lobe-finned fish, as defined by the use of the 3ʹ exonuclease Pnldc1 for precursor piRNA trimming. The nuclear pathway evolved during early in tetrapod evolution and is already found in its current configuration in the salamander, Ambystoma mexicanum. Interestingly, the nuclear pathway was lost during bird evolution. We found evidence that both the cytoplasmic and nuclear piRNA pathways are active in both the male and female axolotl germlines. Analysis of axolotl testes and oocytes revealed diverse repertoires of piRNAs and persuasive post-transcriptional targeting of young transposons. We found high levels of genome methylation in axolotl spermatozoa with full-length transposons being highly methylated. Furthermore, CpG island methylation in axolotl is associated with transposon silencing. In summary, we find that the mammalian version of the piRNA pathway has ancient vertebrate origins, and it has been safeguarding the germline across most of tetrapod evolution.

overall_design: Small RNA-seq was performed on axolotl testis and oocyte samples, each with two biological replicates. EM-seq was performed on axolotl spermatozoa with three biological replicates. Samples were collected from the d/d white axolotl strain with hCG (human chorionic gonadotropin) injection to induce gamete maturation in adult axolotl.

first: Donal

last: O'Carroll

first: Diego

last: Rodriguez Terrones

first: Francisco

last: Falcon


title: Digital transformation of herbal medicine: Conversion to biological entity data using digestive herbal medicine-induced transcriptome sequencing_second_SW1783

first: Musun

last: Park

institute: Korean Institute of Oriental Medicine

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

overall_design: Refer to individual Series


title: CD8+ T cells in the tumor immune microenvironment modulate resistance to endocrine therapy in hormone receptor-positive breast cancer [GeoMx]

status: Public on Oct 07 2025

city: Dallas

first: Fabiana

last: Napolitano

state: TX

address: 6000 Harry Hines Blvd.

institute: Simmons Comprehensive Cancer Center

summary: Enhanced immune infiltration in the tumor immune microenvironment (TIME) is associated with better survival outcomes in patients with triple negative and HER2+ breast cancers. In the hormone-dependent hormone receptor-positive (HR+) subtype, previous studies have identified a subgroup with enhanced immune infiltration. However, the biological significance and role of the TIME in modulating the response to anti-estrogen therapy in breast cancer are not well understood. Herein, using cyclic immunofluorescence and spatial transcriptomics (ST), we dissected the TIME in primary breast cancers that were sensitive or resistant to estrogen deprivation (ED) induced by the aromatase inhibitor letrozole. Stromal tumor-infiltrating lymphocytes (TILs) were increased in ED-resistant vs. ED-sensitive tumors. RNA-sequencing from on-treatment tumors showed differentially regulated pathways, including immune-related gene sets, such as upregulation of IFNɣ and IFNα signaling and allograft rejection. Spatial transcriptomics using GeoMx identified increased antigen processing and immune gene expression signatures in both cancer cells and neighboring immune cells in ED-resistant vs. ED-sensitive tumors. Using CIBERSORT, we uncovered a differential distribution of immune cell subtypes, with CD8+ T cells being enriched in ED-resistant tumors and Tregs in ED-sensitive tumors. The expression of chemokine genes involved in CD8+ T cell recruitment, CXCL9, CXCL10, and CXCL11, was upregulated in ED-resistant primary tumors before and after letrozole treatment. Additionally, CXCL11 levels were higher in media conditioned from HR+ breast cancer cells co-cultured with CD8+ T cells. Both recombinant CXCL11 and co-culture with CD8+ T cells stimulated the growth of HR+ breast cancer cells when deprived of estrogen, akin to the scenario of patients treated with letrozole. Taken together, these data suggest that CD8+T cells in the TIME modulate the response of HR+ breast cancer cells to therapeutic estrogen suppression.

overall_design: To investigate the composition of the TIME in HR+ BC sensitive or resistant to estrogen deprivation (ED), and explore possible mediator of resistance to ED

first: Yunguan

last: Wang

first: Ariella

last: Hanker

first: Carlos

last: Arteaga


title: Chemotherapy-induced CAR cell senescence disrupts bone homeostasis to induce bone loss

city: St. Louis

first: Ganesh

middle: Kumar

last: Raut

address: Euclid Ave

institute: Washington University School of Medicine

summary: To identify which bone resident cells senesced in response to chemotherapy, we performed scRNA-Seq on bone marrow depleted of CD45+, CD71+, Ter119+, CD31+ cells. Our scRNA-Seq analysis identified seven clusters in both Veh- and Doxo-treated mice: CAR cells, three fibroblast populations, chondrocytes, endothelial cells, and osteoblasts that were identified based on cell specific markers. Next, we assessed the expression of the senescence markers (p16 and p21), cell proliferation marker (Mki67) and SASP factors (IL6, Spp1, Cstb, Serpine1, Mmp3). As expected, we found a down regulation of Mki67 and upregulation of senescence markers and SASP factors in the Doxo-treated group compared to Veh. we also checked senescence markers across the clusters and found CAR cells undergo senescence and impact bone homeostasis.

overall_design: 12-week-old mice were treated with Veh- and Doxo (10 mg/kg) for 96 hours. Bones (femurs and tibias) were harvested from euthanized mice and placed in cold DMEM/F12 (Gibco). Muscle and connective tissues were removed. Bones were gently ground and then cut into small fragments. Fragments were transferred and digested with fresh 2 mg/ml collagenase (Sigma, C0130) in DMEM/F12 on a rotating water bath at 37°C for 30 min. Following the first digestion, the released cell suspension was filtered through a 70-μm nylon mesh into a collection tube and placed on ice. A second digestion of the remaining fragments was performed and the cell suspension was filtered into the same collection tube. Reactions were quenched with FACS buffer (PBS plus 0.5% BSA) with 2mM EDTA. Following FACS buffer wash and RBC lysis, dissociated cells were labeled with anti-CD45 magnet microbeads and enriched into a CD45+ fraction and CD45- fraction by MACS (magnetic-activated cell sorting, Miltenyi Biotech). Cells were stained with fluorochrome antibodies for 20 min on ice for cell sorting. We used CD45, CD71, Ter119 and CD31 to deplete CD45+ CD71+, Ter119+, CD31+ populations using a BD FACS Aria III Cell Sorter. After sorting, cells were delivered for library construction using 10X Genomics Chromium 3′ GEM Single-Cell Library v3 kit (10X Genomics).

last: Kumar Raut

first: Zhangting

last: Yao

first: Sheila

last: A Stewart


title: CD8+ T cells in the tumor immune microenvironment modulate resistance to endocrine therapy in hormone receptor-positive breast cancer

first: Ariella B.

first: Carlos L.


title: In vivo differentiation of embryonic cells devoid of key reprogramming factors

status: Public on Oct 05 2025

city: New Haven

first: Scott

middle: Elliot

last: Youlten

state: CONNECTICUT

address: 333 Cedar Street, SHM-I

institute: Yale University

summary: Embryonic cell differentiation depends on the reprogramming of the oocyte and sperm nucleus into a transient totipotent state. In zebrafish, this coincides with genome activation, which is regulated by the pioneer factors Nanog, Pou5f3, and Sox19b (NPS). Here, we investigate the role of NPS in developmental reprogramming and differentiation by analyzing the fate of NPS mutant cells in a wild-type embryo using single-cell RNA-seq. We find that many cells fail to activate transcription or undergo cell death, while others acquire gene expression profiles that resemble germ cells, neural progenitors, and motoneuron states. These cells achieve intermediate transcriptional states revealing the essential role of NPS in coordinating nuclear and cytoplasmic reprogramming and preventing the premature activation of lineage-specific differentiation programs. These results demonstrate that most developmental programs require developmental reprogramming by NPS, yet some cell can bypass transient totipotency to achieve intermediate developmental states resembling wild type states in vivo.

overall_design: Donor embryos (WT or MZnps mutants) were injected with fluorescent reporters and transplanted into host wild-type embryos at the 1-cell stage. Embryos were dissociated at 11–12 hpf and enriched for donor-derived cells using hCD4 magnetic selection. Single-cell suspensions were loaded onto 10x Genomics Chromium chips (v3 chemistry), and three libraries were sequenced (two MZnps donor replicates, one WT donor).

middle: E

first: Liyun

last: Miao

first: Caroline

last: Hoppe

first: Curtis

last: Boswell

first: Damir

last: Musaev

first: Mario

last: Abdelmessih

first: Damilola

last: Olowookere

first: Linnea

last: Weiss

first: Smita

last: Krishnaswamy

first: Antonio

middle: J

last: Giraldez

first: Valerie

last: Tornini


title: Molecular remodeling of myocardium in mice with melanocortin-4 receptor deletion before cardiac function impairment

status: Public on Oct 11 2025

city: Jining

first: Xiaomei

last: Wang

address: No. 133 Hehua Road，Taibai Lake New District

institute: Jining Medical University

summary: The melanocortin-4 receptor (MC4R) is highly expressed in the hypothalamus and mutations in this gene are closely associated with the development of hereditary obesity and early onset severe obesity in humans. It has been demonstrated that Mc4r is involved in the development of dilated cardiomyopathy. However, the current system of early diagnosis and treatment of heart disease is not well established. In this study, we analyzed the effects of Mc4r knockout on cardiac function and cardiomyocyte morphology, fibrosis, and apoptosis in mice. Meanwhile, we explored the possible early molecular mechanisms of Mc4r affecting cardiac dysfunction by transcriptome sequencing of cardiac cells combined with bioinformatics analysis. The results showed that although the overall heart does not show organic changes, our study suggests that cardiomyocytes already show abnormal changes at the early molecular level. The sequencing results showed that the differentially expressed genes between the two groups of mice were mainly enriched in the p53 signaling pathway and HIF-1 signaling pathway. We screened 10 key target genes using PPI network and Module analysis. Subsequently, drugs targeting key genes were screened and seven genes were identified as potential drug targets. This study will provide important reference and guidance for early prevention, treatment and drug targeting of heart-related diseases caused by Mc4r gene deletion.

overall_design: To investigate the role of Mc4r in the development of early cardiac disease, We constructed Mc4r knockout mice. Comparative gene expression profiling analysis of RNA seq data for heart tissues of 12 week old Mc4r knockout mice (MC4R_KO, n=3) and wild-type mice (WT, n=3)


title: Longitudinal single-cell transcriptomics of monocytes, Tfh and gd Tcells following a control human malaria infection.

city: Brisbane

first: Zuleima

last: Pava Imitola

state: Queensland

address: 300 Herston road

institute: QIMR Berghofer

summary:
Malaria infection drives tolerogenic cell responses which protects from high inflammation and immunopathogenesis but reduces  parasite control and adaptive immunity. Here, we comprehensively map responses across innate and adaptive cells.
The results of this Controlled Human Malaria Infection study are presented in three independent publications.

Blood samples from 4 donors were collected prior to infection (day 0), at peak infection (day 8) and 14 or 15 and 27-36 days (end of study, EOS) after inoculation (in analyses these time points are grouped as 0, 8, 14/15 and EOS).  Participants were healthy malaria naïve adults with no prior exposure to malaria or residence in malaria-endemic regions.  For trials NCT02867059, NCT02783833, NCT02431637 all participants received the same study drug (no-randomization) and 3D7-strain parasites. For NCT02431650, participants were randomized 1:1 to receive study drug or control and 3D7-strain parasites. Samples used here were from samples opportunistically collected from volunteers who consented to donate blood for immunological studies within the parent clinical trial. As such, no sample size estimation was performed for this immunology study.

overall_design:
In brief, healthy malaria naïve adults with no prior exposure to malaria or residence in malaria-endemic regions underwent CHMI with 2800 viable P. falciparum parasitized RBCs, and peripheral parasitaemia was measured at least daily by qPCR as described previously (53). Participants were treated with antimalarial drugs at day 8 of infection when parasitaemia reaches approximately 20,000 parasites/ml.
PBMCs were isolated by Ficoll-Paque (Sigma, USA) density gradient centrifugation, isolated PBMCs were cryopreserved in 10% DMSO/FBS. Monocytes, Tfh and GD-T cells from 4 individuals with P. falciparum infection were collected at day of infection (day 0), peak parasitaemia and before treatment at (day8), and day 16 and 36 days post-infection. PBMCs were isolated by Fluorescence-activated cell sorting (FACS) and analysed using droplet-based scRNAseq.”

first: Michelle

last: Boyle

first: Nick

last: Dooley

first: Megan

last: Soon

first: Jessica

middle: R

last: Loughland

last: Pava

first: Julianne

last: Hamelink

first: Kiana

last: Berry

first: Dean

last: Andrew

first: Arya

last: SheelaNair

first: Kim

last: Piera

first: Timothy

last: Williams

first: Bridget

last: Barber

first: Matt

last: Grigg

first: Chris

last: Engwerda

first: Alejandro

last: Lopez

last: Anstey


title: HDAC5 Deficiency Induces Intrinsic Resistance to KRASG12D Inhibition by Disrupting c-Myc Acetylation-Ubiquitination Homeostasis [RNA-seq]

status: Public on Oct 04 2025

city: Wuhan

first: Haixin

last: Yu

state: Hubei Province

address: 1277, Jiefang Avenue

institute: Wuhan union hospital

summary: We found that HDAC5 deletion significantly enhances intrinsic resistance to MRTX1133 in KRASG12D mutant pancreatic cancer. Mechanistic studies show that HDAC5 deletion promotes resistance to KRASG12D inhibitors by sustaining the activation of the MAPK signaling pathway.

overall_design: RNA-seq analysis was performed on AsPC-1 cells, transfected with shNC or shHDAC5 and treated with DMSO or MRTX1133, to investigate their effects on the transcriptome.

first: Zhou

last: Yingke

first: Yu

last: Haixin


title: HDAC5 Deficiency Induces Intrinsic Resistance to KRASG12D Inhibition by Disrupting c-Myc Acetylation-Ubiquitination Homeostasis [RNA-Seq]

overall_design: RNA-seq analysis was performed on tumors from KPC WT and Hdac5 KO mice, as well as on PANC-1 cells transfected with shNC or shHDAC5, to investigate transcriptomic changes following HDAC5 knockdown.

first: Yingke

last: Zhou


title: HDAC5 Deficiency Induces Intrinsic Resistance to KRASG12D Inhibition by Disrupting c-Myc Acetylation-Ubiquitination Homeostasis [ChIP-Seq]

overall_design: ChIP-seq was performed on PANC-1 cells transfected with shControl-1,shControl-2,shHDAC5-1, or shHDAC5-2 to investigate the impact of HDAC5 knockdown on MYC chromatin binding.


title: Sox11 overexpression restores embryonic pro-growth transcription in mature corticospinal tract neurons.

city: Milwaukee

first: Murray

last: Blackmore

state: WI

address: 561 N 16th St

department: Biomedical Sciences

institute: Marquette University

summary: Neurons in the central nervous system (CNS) display a high capacity for axon growth during early development but mostly lose this ability during a key stage of differentiation marked by synaptic maturation, circuit integration, and a profound shift in gene transcription. Once mature, neurons largely fail to reverse this transcriptional switch after axon injury, fundamentally constraining their intrinsic capacity for repair. Here, we show with single-nucleus RNA sequencing that forced expression of the transcription factor Sox11 in adult corticospinal tract neurons produces large-scale and stable changes in gene expression that are highly enriched for growth-relevant processes, and which strongly resemble those of pre-synaptic embryonic stages. Moreover, Sox11 is equally effective when delivered to chronically injured CST neurons. These data reveal Sox11’s ability to reverse a critical step of neuronal maturation even in otherwise unperturbed neurons, clarifying the transcriptional underpinnings and highlighting Sox11’s potential as a pro-regenerative stimulus.

overall_design: In adult mouse samples, corticospinal tract (CST) neurons were transduced with a retrograde, nuclear-localized fluorophore (mGl) and control or Sox11-expressing virus by retrograde transduction from cervical spinal cord. Animals recevied either no injury or a cervical contusion injury six weeks prior to tissue collection. Animals that received Sox11 and no injury were collected at four time points: 1 week, 2 weeks, 4 weeks, or 6 weeks after viral delivery, with each time point uniquely barcoded and pooled in the same sequencing reaction. Embryonic cortex was collected at embryonic day 18. For all samples, single nucleus RNA sequencing was performed. Adult samples were pre-purified using fluorescent activated nuclei sorting prior to library preparation. E18 embryonic libraries were prepared from ixed cortical tissue.

first: Elizabeth

last: Batsel

first: Zimei

last: Wang

last: Otten

first: Rabia

last: Mohammad

first: Paula

last: Pascal

first: Darby

last: O'Shea

first: Jose

last: Rosas

first: Pantelis

last: Tsoulfas


title: Tanshinone IIA inhibits heat-induced growth of p53-mutant Huh-7 hepatocellular carcinoma by modulating osmotic homeostasis and glycolysis through targeting ALDH7A1

status: Public on Oct 03 2025

city: Zhengzhou

first: Xuhua

last: Duan

address: No. 1 Longhu Middle Ring Road, Jinshui District

institute: The First Affiliated Hospital of Zhengzhou University

summary: Thermal ablation offers minimally invasive treatment options for hepatocellular carcinoma (HCC) therapy. However, local recurrence due to sublethal temperatures enhances tumor cell survival. This study aims to investigate the tumor-promoting effects of hyperthermia on HCC cells, the role of tanshinone IIA (Tan IIA) in mitigating these effects, and the underlying mechanisms involved. We observed that temperature at 44 °C increased the aggressiveness of HCC cells, and Tan IIA inhibited cell viability and cell invasion, and induced cell cycle arrest and apoptosis of heat-pretreated HCC cells. ALDH7A1 was identified as a target of Tan IIA, and its altered expression resulted in dysregulation of cell viability, invasion, apoptosis, ATP production, glycolysis, osmolyte levels, and reactive oxygen species (ROS). Under hyperosmotic conditions, ALDH7A1 knockdown sensitized heated Huh-7 cells, while its overexpression promoted cell survival and invasion, with corresponding changes in energy metabolism and enzymatic products. Tan IIA and the specific ALDH7A1 inhibitor, 4-diethylaminobenzaldehyde, demonstrated similar effects on gene expression patterns, glycolysis, osmotic regulation, and ROS levels in heated Huh-7 cells. Moreover, Tan IIA is able to direct interact with ALDH7A1 protein. In vitro, Tan IIA combined with hyperosmotic stress significantly inhibited cell invasion and induced apoptosis in heat-induced Huh-7 cells and ALDH7A1 overexpression partially reversed the effects of Tan IIA. In vivo, Tan IIA combined with hyperosmotic stress or glycolysis inhibitor yielded better therapeutic efficacy for HCC. In conclusion, Tan IIA sensitizes HCC cells to sublethal heat by targeting ALDH7A1, leading to disrupted glycolytic and osmolytic balance, subsequently hindering tumor cell survival and increasing apoptosis. These findings highlight a potentially novel strategy for preventing or treating recurrent HCC post-thermal ablation using Tan IIA with hyperosmotic reagents.

overall_design: Total RNA was extracted from Huh-7 and Hep-G2 cells using the TRIzol reagent (Invitrogen). The cells were treated under various conditions as described: a blank control; exposure to 8 μM Tan IIA for 48 hours; treatment with 8 μg/mL 4-diethylaminobenzaldehyde (DEAB) for 48 hours; shALDH7A1 infection for 48 hours; preheating at 44 °C (Huh-7) or 45 °C (Hep-G2) for 10 min; and 8 μM Tan IIA treatment for 48 hours following preheating at 44 °C for 10 min.

first: Hao

last: Li

first: Shuguang

last: Ju

first: Jiacheng

first: Donglin

last: Kuang

first: Pengfei

last: Chen

first: Mengfan

last: Zhang

first: Ruijie

last: Qian

first: Chao

last: Liang

first: Daqian

last: Han


title: Reprogramming of disease tolerance is necessary for infection defense during aging

city: San Diego

first: April

middle: Elizabeth

last: Williams

state: California

address: 10010 N Torrey Pines Rd

department: IGC

institute: Salk Institute for Biological Studies

summary: Cardiac gene expression of old and young C57Bl/6 mice infected with the LD50 dose of polymicrobial sepsis and age-matched uninfected controls.

overall_design: 12- and 75-week-old B6 mice were infected with the LD50 dose of 1:1 mixture of E. coli and S. aureus. When the morbid mice reached maximal morbidity in each age group, the hearts were harvested from the morbid-infected, healthy-infected and age-matched uninfected control mice for RNAseq.

first: Karina

last: Sanchez

first: Justin

last: McCarville

first: Sarah

last: Stengel

first: Janelle

last: Ayres


title: Investigation of the Regulatory Mechanism of Dhx37 in Sertoli Cells Using snRNA-seq

status: Public on Oct 02 2025

city: Luoyang

first: Yuqing

last: Jiang

address: No. 263, Kaiyuan Avenue, Luolong District

institute: The First Affiliated Hospital, and College of Clinical Medicine of Henan University of Science and Technology

summary: To investigate the regulatory mechanism of Dhx37 in Sertoli cells, snRNA-seq analysis was performed on testicular cells isolated from whole testes of wild-type and Dhx37-/- mice (CKO)at P60. After quality control, single-cell transcriptomes for both wild-type and Dhx37-/- mice were obtained. UMAP dimension reduction and visualization categorized the cells into ten distinct clusters: Round Spermatids, Elongating Spermatids, Spermatocytes, Spermatogonia, Leydig cells, Fibroblasts, Sertoli cells, Macrophages, Endothelial cells, and others, based on known marker genes.

overall_design: Testicular cells were isolated from 8-week-old wild-type and Dhx37-/- mice following the snRNA-seq  procedure.

first: Huifang

last: Peng

first: Hongwei


title: CAGE-seq Profiling of Transcription Start Site Usage in mock-infected and human cytomegalovirus (HCMV) infected human embryonic lung fibroblasts (HELF) cells at 12h and 72h post-infection (human)

status: Public on Oct 01 2025

city: Shenyang

first: Yang

address: No. 36. Sanhao street, Heping District

institute: Shengjing Hospital of China Medical University

summary: CAGE-seq (Cap Analysis of Gene Expression coupled with deep sequencing) was used to map transcription start site (TSS) usage in human embryonic lung fibroblast (HELF) cells in response to infection with the human cytomegalovirus (HCMV) HAN strain. HELF cells were mock-infected or infected at a multiplicity of infection (MOI) of 3 and harvested at 12 hours post-infection (12 hpi) or 72 hours post-infection (72 hpi). This study provides genome-wide profiles of active promoters and capped 5' transcript ends to investigate dynamic changes in TSS usage during HCMV infection.

overall_design:
Human embryonic lung fibroblasts (HELF) were subjected to three conditions: mock infection, HCMV infection for 12 hours, and HCMV infection for 72 hours. Cells were infected with HCMV HAN strain (MOI=3) where applicable. Total RNA was isolated from each condition and used to generate CAGE libraries capturing the 5' ends of capped transcripts. Sequencing was performed on the Illumina HiSeq X Ten platform (150 bp paired-end reads). The primary experimental variables are infection status (mock vs. HCMV) and time post-infection (12 h vs. 72 h), with mock-infected HELF cells serving as the control.
Raw data uploaded to SRA under Bioprojects: PRJNA1299111; PRJNA1291936; PRJNA1441831

first: Yanping

last: Ma

first: Qiang

last: Ruan

first: Zhongwei

last: Zhao


title: Paternal microplastic exposure alters sperm small non-coding RNAs and elicits offspring metabolic dysfunctions in mice

city: Riverside

first: Changcheng

last: Zhou

address: 900 University Avenue

department: School of Medicine

institute: University of California, Riverside

summary: Microplastics (MPs) has been known for its toxicity on various organs and cells in humans, and its exposure leading to disease. Nevertheless, the toxic effects and underlying mechanisms on the profile of small non-coding RNAs (sncRNAs) in sperm, as well as their effects on embryo development, are not well understood. We recently developed the novel RNA sequencing (RNA-seq) technique, PANDORA-seq to overcome the limitations of traditional RNA sequencing. In this study, we elucidated the sncRNA changes using PANDORA-seq in mouse sperm after four weeks of oral gavage with MPs. We also examined the effects of sncRNAs on mouse embryonic stem cells (mESCs). MP exposure significantly altered sncRNA biogenesis-related genes in the testis and cauda epididymis, but not in the caput epididymis. PANDORA-seq revealed that a sncRNA landscape including transfer RNA-derived small RNAs (tsRNAs) and ribosomal RNA-derived small RNAs (rsRNAs) in the sperm was changed by MPs gavage. Interestingly, transfections of changed sncRNA, tsRNA-Glu-CTC and 5S ribosomal RNA (5S rRNA), in mESC changed pluripotency, inflammation, and cardiovascular development related genes. In conclusion, exposure to MPs may alter the sncRNA profile in sperm, which could affect embryonic development and increase the risk of inheritable diseases such as atherosclerosis and metabolic disorders.

overall_design: To investigate the potential effects of MPs exposure on offspring health, 8-week-old male C57BL/6J WT mice were orally gavaged with either water or 10 mg/kg body weight/day of polystyrene microplastics (MPs, 1.1 μm mean particle size) for 4 weeks before mating with 12-week-old unexposed female WT mice. We profiled the sncRNA changes using PANDORA-seq in mouse sperm after 4 weeks of oral gavage with MPs to link the metabolic phenotype observed in F0 males with their offsprings. In addition, we also examined the effects of altered sncRNAs on mouse embryonic stem cells (mESCs).

first: Seung Hyun

last: Park

first: Jianfei

last: Pan

first: Xudong

first: Ting-An

last: Lin

first: Sijie

last: Tang

first: Tong

first: Qi


title: Nanoparticle immunoadjuvant complexes augment antigen-specific germinal center responses and enhance humoral immunity

city: Philadelphia

first: Priyankara

last: Wickramasinghe

state: PA

address: 3601 Spruce Street

institute: The Wistar Institute

summary: An alluring strategy for improving protective humoral immunity against infectious diseases would be to directly target the germinal center (GC). There remains a critical need for next generation vaccine approaches to elicit more potent GC responses and durable humoral immunity. Here, we investigated whether cytokines could be scaffolded on nanoparticles to further enhance antigen-specific GC responses. We designed a chimeric nanoparticle using the GT8-60mer, a germline-targeting HIV immunogen, as a model to scaffold IL-21. Nanoparticle immunoadjuvant complexes (NICs) scaffolding GT8 and IL-21 (GT8-IL-21-NIC) drove improved serum antibody titers, antigen-specific GC B cells, and functional Tfh cell responses relative to antigen-only nanoparticles and to co-delivery of IL-21 monomer. Single-cell RNA sequencing of antigen-specific GC B cells from GT8-IL-21-NIC immunized mice demonstrated upregulation of LZ and selection-associated gene signatures. The NIC platform was versatile and could support changes to both the antigen and cytokine domains utilizing numerous GC-associated cytokines. Thus, NICs may provide value as a tool to improve antigen-specific vaccine-induced immunity.

overall_design: Single Cell RNA-Seq of antigen-specific germinal center B cells sorted from lymph nodes of mice immunized with a DNA-launched nanoparticle vaccine or DNA-launched nanoparticle immunoadjvuant complex (NIC)

first: Nicholas

last: Tursi

first: Daniel

last: Kulp

first: David

last: Weiner


title: Regulatory T cell stability determines the efficiency of bile duct regeneration during cholangitis.

city: Edinburgh

first: Wei-Yu

last: Lu

address: 4-5 Little France Drive

department: Institute for Regeneration and Repair

institute: University of Edinburgh

summary: Cholangiopathies such as Primary Sclerosing Cholangitis (PSC) cause damage to the bile ducts and fibrosis with no effective cure. A reduction and impairment in the function of regulatory T cells (Tregs) occur in PSC. Yet, it is currently unknown what consequence this has on bile duct regeneration. We investigate whether Tregs regulate bile duct regeneration and the dynamics of Tregs turnover during bile duct injury. We used the transgenic Foxp3GFPDTR model to mimic reduced Tregs infiltration to the liver during bile duct injury and showed that reduced intrahepatic Tregs limits bile duct regeneration. Fate mapping of Tregs (Foxp3CreERTAi14) showed that Tregs acquire a pro-inflammatory phenotype within the inflammatory microenvironment, even after IL2 mediated Tregs expansion. Ox40L expression correlates with fibrosis in PSC patients. In the 3,5-Diethoxycarbonyl-1,4-Dihydrocollidine (DDC)-diet mouse model of experimental cholangiopathy, combining IL2-complex administration and blocking Ox40L decreases periportal fibrosis level, increases Treg number and reduces the pro-inflammatory phenotype of Tregs. These results indicate that Tregs mediate cholangiocyte response to biliary injury, and Tregs downregulate Foxp3 and acquire an inflammatory phenotype in an inflammatory microenvironment. Enhancing Treg numbers through IL2 complex administration and blocking Ox40 signalling simultaneously suppress the inflammatory phenotype of Tregs and reduce bile duct damage and fibrosis.

overall_design: Bulk RNA sequencing of freshly isolated EpCAM+ cholangiocytes from transgenic Foxp3GFPDTR  mice which received DDC diet for 10 days. PBS / 1ug/kg Diphteria Toxin was given intraperitoneally  every 48 hours after the commence of DDC diet.

first: Naruhiro

last: Kimura

first: Man Chun

last: Wong


title: Ablation of CD38 on Multiple Myeloma Cells Leads to an Aggressive Phenotype

city: St Louis

first: Mikhail

last: Berezin

state: Missouri

address: 4515 McKinley  Ave

institute: Washington University in St. Louis

summary: Multiple myeloma (MM), the second most common hematological cancer in the United States, is characterized by the proliferation of malignant clonal plasma cells primarily within the bone marrow. The multifunctional cell surface glycoprotein CD38 is expressed in majority of MM cells, making it a key biomarker. Since the FDA approval of daratumumab in 2015, CD38-targeted immunotherapies have significantly advanced the treatment of MM; albeit nonuniform patient response and relapse. The role of CD38 in the complex bone microenvironment remains under investigation. This study examined the effect of CD38 on tumor cells by evaluating a CD38 knock-out (KO) clone of a human MM cell line xenografted into immunodeficient mice. CRISPR/Cas9 gene editing was used to KO CD38 expression in the wild-type (WT) MM.1S human MM cell line (MM.1S-CBR-GFP), confirmed with RNA sequencing and flow cytometry. After tumor implantation in mice, bioluminescence imaging (BLI) was employed to track tumor cells. Small animal Positron Emission Tomography (PET) was performed with the metabolic tracer, fluorodeoxyglucose ([18F]-FDG), and CD38-targeted [89Zr]-Daratumumab, respectively. Post-PET tissue biodistribution and leg bone autoradiography was performed to evaluate tracer distribution. Computed Tomography (CT), dual-energy X-ray (DEXA), and immunohistochemistry were used to evaluate changes in bone mineral density and osteolytic disease. Differences in blood composition, cytokine production, and RNA sequencing between WT and KO mice were analyzed for characterizing the new CD38 KO phenotype. BLI showed significantly increased tumor burden in the CD38 KO MM models compared to WT mice after implantation: 1-week (P=0.0011), 2-weeks (P=0.0066), 3-weeks (P=0.0046), and 4 weeks (P<0.0001). CT and DEXA imaging revealed that the KO mice had significantly decreased bone density, and similarly, planar X-ray imaging indicated severe myeloma bone disease characterized by cortical and trabecular osteolytic lesions in the femur and tibia. Bone histology further confirmed the KO tumor more aggressively invading the bone and muscle tissue. [89Zr]-Daratumumab accumulated in the spine, femur, and tibia in WT MM mice, with minimal bone uptake in the CD38 KO MM mice. [18F]-FDG PET revealed an increased metabolic activity of CD38 KO MM, with an aggressive kinetic uptake of the tracer (P < 0.001). Bilateral kidney metastases were observed in nearly all CD38 KO MM mice, while remaining undetected in WT mice. Blood analysis indicated elevated markers of disease progression and renal dysfunction, with reduced leukocyte and thrombocyte production in the CD38 KO MM xenografts. Cytokine profiling revealed altered levels of pro-inflammatory cytokines, including IL-13, IL-6, RANKL, and VEGF-α in the bone microenvironment of MM with depleted CD38. RNA sequencing showed significant transcriptional changes in CD38 KO cells, suggesting that the observed enhanced aggressiveness is predominantly fueled by the activation of key pathways that promote accelerated cell proliferation, pathways that enhance osteoclast activity, and pathways that enhance metastatic potential.

overall_design: The human MM cell line, MM.1S, was obtained from Professor Katherine N. Weilbaecher in the Department of Medicine at Washington University School of Medicine (WUSM) and has been previously used to develop MM models.12, 13 The cell line was transduced with a lentivirus encoding green fluorescent protein (GFP), to enable visualization of cellular localization, and click beetle red (CBR), luciferase for bioluminescence-based tumor burden quantification and real-time monitoring of disease progression. The WT MM.1S cell line (MM.1S-WT-GFP-CBR) was genetically modified using CRISPR/Cas9 gene editing, performed by the McDonnel Genome Institute at WUSM, to create a CD38 KO clone (MM.1S-CD38 KO-GFP-CBR). The CD38 KO clone was expanded in bulk culture until sufficient cell aliquots were available for cryopreservation in liquid nitrogen. Similar to the WT MM.1S cell line, the CD38 KO clone cell line was tagged with GFP and CBR for visualization and bioluminescence analysis. RNA sequencing between WT and KO cells was performed to characterize the new CD38 KO phenotype. There were 6 RNA samples, 3 WT MM.1S cells and 3 CD38 KO cells.

first: Michael Riley

last: Dyer

first: Alex

last: Zheleznyak

first: Erin

last: Teubner

first: Julie

last: Prior

first: Brad

last: Manion

first: Han

last: Jing

first: Amit Kumar

last: Sharma

first: Junwei

last: Du

first: Deborah

last: Veis

first: John

middle: F

last: DiPersio

first: Rui

last: O’Neal

middle: Y

first: Monica

last: Shokeen


title: Ribosomal heterogeneity revealed by a spatial transcriptomics in the water fern Ceratopteris richardii

status: Public on Sep 30 2025

city: Jishou

first: Gui-Sheng

last: Li

address: 120 Renmin South Street

institute: Jishou University

summary: Background and Aims: Ferns are providing insight into fundamental biological processes, and spatial transcriptomics is a potent tool in unraveling complexes of plant development. This research is targeted at leaf development in the water fern Ceratopteris richardii with the use of spatial transcriptomics. Methods: A shoot tip of sporophytes under vegetative growth was investigated using spatial transcriptomics, which conducted spot clustering, marker gene identification, and functional enrichment. Ribosomal protein genes were queried using BLAST program and categorized based on multi-alignment produced by Clustalw2 program. RNA in situ tissue hybridization was performed on three ribosomal protein genes. Key Results: Leaves were mutually different at the level of transcriptome under various developmental stages. There were unexpected complexes in tissue structure for stems. A few transcription factors were identified characteristic of leaf development. Activities associated with translation were very different between tissues, and ribosomal protein genes were heterogeneous at the level of transcription. Ribosomal protein genes were specifically expressed in the shoot apical meristem, leaf primordia, and vasculature of various organs. Conclusions: Leaves are mutually different under various developmental stages in C. richardii, with contribution of transcription factors. Stems are unexpectedly complex in tissue structure. Organs/tissues are very different in translation activity from each other, partly due to transcription heterogeneity of ribosomal protein genes. Ribosomal protein genes are specifically expressed in the shoot apical meristem, leaf primordia, and vasculature.

overall_design: The water fern Ceratopteris richardii was employed, one sporophyte under vegetative growth with three fully expanded leaves was dissected, and the central shoot tip was retained and directly immersed into the optimal cutting temperature compound (OCT, Sakura Finetek Europe B.V.) under dry ice. The specimen was sectioned with a thickness of 20 μm, and the anchored section was fixed on slides using 100% methanol. Topuidine Blue staining was applied for histological examination. RNA was trapped by poly(T)VN to the spot array, namely BMKMANU S1000 platform (BioMarker, Beijing) having a density of more than two million spots with a diameter less than 2.5 μm and 5 μm centre-to-centre distance within 6.8 mm2 area. Double-strand cDNA was synthesized to incorporate the spatial barcode and the unique molecular index (UMI), and furthermore the sample index. The fragmented DNA was obtained via enzymatic digestion, and it was sequenced using NovaSeq PE150 (Illumina). Sequencing reads were mapped to the genome assembly with the accession number of GCA_020310875.1. BSTMatrix (BioMarker) was used to construct the spot-expression matrix under a total of eight levels. The package Seurat v5 provided tools in normalizing data, identifying clusters, and determining marker genes. The threshold for the marker gene was |log2FC| ≥ 0.5 and false discovery rate < 0.05. Spot clustering was visualized using BSTViewer V1.42 (BioMarker). Genes were functionally annotated using multiple platforms such as NR, Pfam, Swiss-Prot, and TrEMBL with the help of the program BLAST, and the subsequent enrichment analysis was conducted using clusterProfiler v3.18.1.

first: Jin

last: Han


title: Fluoxetine promotes recovery from noise-induced cochlear neural degeneration

city: Seongnam

first: Hyun-Ju

last: An

state: --- Select One ---

address: Seongnam-si, 13496

institute: CHA university

summary: Fluoxetine treatment after noise exposure restored cochlear synaptic expression of brevican and decreased low-frequency hearing thresholds. In cochlear nuclei, fluoxetine treatment decreased the expression of PNN and was predicted to upregulate the neuropeptide signaling pathway

first: Hyunju


title: Enhancing PARP inhibitor treatment efficacy for urothelial carcinoma by new biomarkers and synergistic combination treatment with bromodomain protein inhibitor PLX51107

city: Duesseldorf

first: Michèle

last: Hoffmann

state: NRW

address: Moorenstr. 5

department: Urology

institute: Heinrich Heine University, Medical Faculty

summary: We characterized cellular and molecular effects of the PARP inhibitor (PARPi) Olaparib compared to Talazoparib in bladder cancer cell lines and their Cisplatin pre-treated sublines. We aimed to identify common target genes of both PARPi and differences in mechanism of action to understand resistance mechanisms and identify new PARPi response marker for bladder cancer. RNA was submitted to RNA sequencing analysis on the NextSeq2000 system (Illumina).

overall_design: Total RNA from urothelial carcinoma (UC) cell lines T24, T24 Cisplatin resistant cells (LTT), J82, J82LTT and RT112 cells treated with PARPI Olaparib or Talazoparib for 72h and compared to solvent control (DMSO). Triplicates were analysed for each condition.

first: Jutta

last: Schmitz

first: Anna L.

last: Bartkowiak

first: Patrick

last: Petzsch

first: Michael

last: Rose

first: Leandra

last: Lepping

first: Julka

last: Volkamer

first: Karl

last: Köhrer

first: Günter

last: Niegisch

first: Michèle J.

first: Tahlita C.M.

last: Zuiverloon

first: Tokameh

last: Mahmoudi

first: Vandana

last: Solanki

first: Nora

last: Kolks

first: Anne

last: Stoffel

first: Bianca

last: Faßbender

first: Marc

last: Seifert


title: Cleavage under targets & tagmentation (CUT&Tag) sequencing of mouse utricle explants following BMP4 treatment

city: SHANGHAI

first: yunzhong

last: zhang

state: SHANGHAI

address: 83 fenyang road, xuhui district

department: Department of ENT Institute and Otorhinolaryngology

institute: Eye & ENT Hospital of Fudan University

summary: We performed the Cleavage Under Targets and Tagmentation (CUT&Tag) sequencing assay to identify proteins that interact with c-Fos in order to validate the microenvironment stimulation by BMP4.

overall_design: Comparative CUT&Tag analysis was performed by pulling down with an anti-c-Fos antibody and comparing this with a nonspecific negative control IgG.


title: BMP4 regulates transcriptomic changes in mouse utricle

summary: Transcriptomic sequencing data encompassing the process of inner ear vestibular hair cell regeneration under the regulatory effects of BMP4.

overall_design: To explore the molecular mechanism through which BMP4 functions in inner ear progenitor cells, we performed bulk RNA-sequencing to assess changes in downstream transcriptional networks.


title: Fibroblast-directed melanocyte recruitment via Cxcl12-Cxcr4 cascade promotes post-inflammatory hyperpigmentation and skin barrier protection in zebrafish

city: Shenzhen

first: Zhao

last: Shizheng

address: Shenzhen

department: LIFS

institute: Undefined

summary: Post-inflammatory hyperpigmentation (PIH) is a common skin disorder characterized by brown or black macules. It can be categorized as transient, typically resolving within 6–12 months, or permanent, persisting for years. While the pathogenesis of PIH is commonly linked to localized melanocyte overactivation, the precise cellular and molecular basis for this dysregulation, as well as its physiological significance, remains poorly defined. Using an acetic acid-induced zebrafish model, we identify melanocyte migration as a critical driver of hyperpigmentation. This process is independent of immune cells but driven by fibroblasts, which secrete Cxcl12a to recruit melanocytes via the Cxcl12a–Cxcr4a axis. Fibroblast ablation irreversibly disrupts melanocyte patterning, indicating that aberrant fibroblast activity dictates the permanence of PIH. The recruited melanocytes form a dual protective barrier against both UV-induced DNA damage and microbial intrusion. The translational relevance of this mechanism is underscored by upregulated CXCL12 expression in fibroblasts from human PIH-related conditions such as keloids, acne, and atopic dermatitis. Therapeutically, the FDA-approved CXCR4 antagonist AMD3100 (Plerixafor) effectively prevents and treats PIH in our model. Our findings elucidate a fibroblast-mediated mechanism of melanocyte recruitment in PIH, uncover previously unappreciated barrier functions of melanocytes in skin repair, and propose a promising repurposed treatment strategy.

overall_design: In this experiment, we have conducted acetic acid corrosion in four trunk sites in 2 dpf embryos,cut the trunk region at 3 dpf, dissociated the embryos into single cell suspension and performed FACS sorting of dsRed positive fibroblasts. In each biological replicate, around 30 embryos were harvested and 500 fibroblsts were sorted into lysis buffer. Smartseq2 protocol was utilized for double strand cDNA library construction.

first: Shizheng

last: Zhao

first: Zilong

last: Wen


title: Impact of hyaluronic acid coating of collagen membranes: RNAseq of gingival fibroblasts

status: Public on Sep 29 2025

city: Vienna

first: Reinhard

last: Gruber

address: Sensengasse 2a

country: Austria

institute: Medical University Vienna

summary: Collagen membranes are commonly used biomaterials in clinical dentistry that can be coated with hyaluronic acid (HA). To investigate fibroblast responses, gingival fibroblasts were seeded on porcine-derived membranes originating from dermis (Mucoderm®) and pericardium (Collafleece®) —with or without lyophilized HA, followed by bulk RNA sequencing. Mucoderm® and Collafleece® elicited a significant transcriptional response compared to fibroblasts grown on tissue culture surfaces. Compared to Mucoderm®, Collafleece® increased the expression of extracellular matrix genes CCN1, CCN2, COL1A1, POSTN, SPARC, TAGLN, FBN2, CCDC80 and CREB3L1. Decreased genes included the proteases MMP3 and MMP10 but also detoxifying genes MT1E, MT2A, HMOX1, NQO1. RNA sequencing further revealed that HA coating increased IL24 in Mucoderm®, but no increasing changes was observed in Collafleece®. These data suggest that Collafleece® has a comparably stronger positive impact on extracellular matrix formation by in gingival fibroblast than Mucoderm®. The results further imply that HA coating does consistently impact fibroblast behavior.

overall_design: We exposed gingival fibroblasts on porcine-derived membranes originating from dermis (Mucoderm®) and pericardium (Collafleece®) —with or without lyophilized HA, followed by bulk RNA sequencing, to identify changes in the genetic signatures of fibroblasts.

first: Panahipour

last: Layla

first: Xiaoyu

last: Huang


title: 4R-Tau Seeding Activity Reveals Molecular Subtypes in Progressive Supranuclear Palsy

city: London

first: Tallulah

middle: Suzanne

last: Andrews

state: Ontario

address: 1151 Richmond St.

institute: University of Western Ontario

summary: Progressive Supranuclear Palsy (PSP) is a clinically heterogeneous 4-repeat (4R)-tauopathy marked by variable progression and phenotypic diversity. We examined the distribution of high-molecular-weight tau (HMW-tau) species and 4R-tau seeding capacity across 25 PSP cases and 20 brain regions. HMW-tau levels varied regionally, with the temporal and motor cortices exhibiting the highest abundance. Using size-exclusion chromatography (SEC) and 4R-tau seed amplification assays (SAAs), we identified that HMW-tau fractions exhibit the greatest seeding activity. Proteomic and spatial transcriptomic analyses of the primary motor cortex revealed dysregulated adaptive immunity and metabolic pathways in high-seeder cases. Neuropathological clustering confirmed distinct profiles associated with tau seeding activity. These findings suggest that evaluating tau seeding capacity may offer valuable insights into the heterogeneity of PSP and its underlying molecular drivers.

overall_design: Post-mortem tissue sections from the motor cortex of four patients with Progressive Supranuclear Palsy (PSP) (2 high seeders, 2 low seeders) were selected for spatial transcriptomics based on distinct 4R-tau seeding capacities identified via seed amplification assays. These cases showed comparable PSP stage, phenotype, and co-pathologies. They were also used in neuropathological and proteomic analyses. Tissue quality (DV200 > 50%) ensured suitability for Visium profiling.

first: Ivan

last: Martinez Valbuena

first: Gabor

last: Kovacs