title: Therapeutic effect of  ANGPTL4 antisense oligonucleotide treatment in pneumonia caused by PAO1 bacteria or PR8 virus

city: Singapore

first: Damien

last: Chua

address: 11 Mandalay Road

department: Lee Kong Chian School of Medicine

country: Singapore

institute: Nanyang Technological University, Singapore

summary: A bacterial pneumonia model represented by Pseudomonas aeruginosa (PAO1) or viral pneumonia model by PR8 virus infection were constructed, and then the drug of antisense oligonucleotide(ASO) for ANGPTL4 is administered for treatment. The inflammatory status of mouse lung tissue is analyzed pathologically and the inflammatory cell count is carried out to evaluate the therapeutic effect of the drug. Similarly, the expression of ANGPTL4 protein in mice is detected and its corresponding lung tissues are analyzed for transcriptomic analysis, and its possible functional pathways are further explored and summarized.

overall_design: In PAO1 infection group, we conducted gene sequencing on four distinct groups of samples: PAO1-infected mice treated with ASO(PAO1-ASO), PAO1-infected mice without treatment(PAO1), healthy mice treated with ASO(Ctrol-ASO), and healthy mice without treatment(Ctrl). In the PR8 infection group, we conducted gene sequencing on four distinct groups of samples: PR8-infected mice treated with ASO(PR8-ASO), PR8-infected mice without treatment(PR8), healthy mice treated with ASO(Ctrl-ASO), and healthy mice without treatment(Ctrl). Each group comprised five samples.

first: Haiyang

last: Fan

first: Shumin

last: Liao

first: Liang

last: Li


title: Evidence for coordinate epigenomic roles for CTCF and histone H3.3 in K27M diffuse midline gliomas

status: Public on Mar 24 2026

city: Sacramento

first: Paul

last: Knoepfler

state: CA

address: 2425 Stockton Blvd, Room 633

department: Cell Biology and Human Anatomy

country: USA

institute: University of California Davis

type: Expression profiling by high throughput sequencing

summary: In this study we identified and characterized key chromatin domains in diffuse midline glioma cells, looking at well known types of domains including super enhancers, bivalent domains, and H3K4me3 broad domains as well as the chromatin states identified by chromHMM. In this context, we identified a key role for CTCF in maintaining H3K27me3 levels at bivalent domains, and demonstrated that the H3.3K27M mutation affects both CTCF localization and H3K27me3 at these regions. We further characterized a functional interaction between H3.3 and CTCF in diffuse midline glioma cells, finding that the H3.3K27M mutation affects CTCF localization, leading to an expansion of CTCF-bound domains including a large number of ectopic CTCF binding sites found in H3.3K27M but not WT cells. We also found that CTCF knockdown increases cell viability in H3.3K27M cells, and affected the expression of a set of genes highly enriched in active chromatin states and likely important for some of the oncogenic properties of these cells. Together, our results identified complex chromatin domains defined by combinations of epigenetic modifications, which may have implications for designing therapy regimens that include multiple epigenetic drugs to more effectively target the numerous changes in chromatin observed in glioma cells with H3.3K27M. We also defined an important role for the structural protein and transcription factor CTCF in influencing the epigenetic landscape and transcriptome in the context of the H3.3K27M mutation in diffuse midline glioma cells.

overall_design: RNA-seq was performed in duplicate in DIPG XIII cells with CTCF knockdown or scramble control transfection

first: Rachel

last: Klein


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

city: Fukuoka

first: Shinichiro

last: Sawa

address: 3-1-1 Maidashi, Higashiku

country: Japan

institute: Kyushu University

type: Genome binding/occupancy profiling by high throughput sequencing

summary: Although ILC3s are known to differentiate in RORγt-dependent manner, besides ILC3s, RORγt-dependent developmental program is shared among several lymphocytes.However, little is known about the regulatory mechanism of RORγt expression specific to ILC3s. Our data newly idetified cell lineage-specific and two-step regulation of RORγt expression in ILC3 including LTi cells.

overall_design: To elucidate the regulatory mechanisms of RORγt expression specific to ILC3s, we comprehensively performed ATAC-seq across cell lineages and differentiation stages in RORγt-positive cells

first: Takuma

last: Fukui

first: Miyuki

last: Watanabe

first: Satoshi

last: Kojo

first: Eriko

last: Sumiya


title: Evidence for coordinate epigenomic roles for CTCF and histone H3.3 in K27M diffuse midline gliomas [CUT&RUN]

overall_design: To determine CTCF localization and the effect of the H3.3K27M muation on CTCF localizaion in DIPG cells, CTCF Cut&Run was performed in duplicate in DIPG XIII cells that were either WT for histone H3.3 or contained the H3.3K27M mutation. To determine the effect of loss of CTCF on histone H3.3 and histone modification H3K27me3, Cut&Run was performed in duplicate for both total H3.3 and H3K27me3 after CTCF knockdown and compared to Cut&Run for total H3.3 or H3K27me3 in cells treated with a scramble control siRNA.


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

overall_design: To confirm the maturation of LTi cells with the upregulation of RORγt expression, we performed scRNA seq on LTi progenitor cells sorted from the E14.5 fetal liver based on their levels of RORγt expression.


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

overall_design: RORγt-positive cells differentiated in vitro from CLPs from the fetal liver can be classified into two groups based on Runx3 expression. To investigate the functional differences between Runx3-positive RORγt-positive cells and Runx3-negative RORγt-positive cells, bulk RNA sequencing was performed on each cell population.


title: Spatial transcriptomics of cellular niches in pulmonary granuloma of chronic sarcoidosis patients

city: Hannover

first: Jonas

last: Schupp

address: Carl-Neuberg-Str. 1

department: Respiratory Medicine

country: Germany

institute: Hannover Medical School

summary: Spatial Transcriptomics using the 10x Genomics Visium technology was performed in  lung tissues from 9 patients with chronic sarcoidosis

overall_design: Lung tissue from 9 sarcoidosis patients

middle: C

first: Neubert

last: Lavinia

first: Christian

last: Leonard

first: Yilmaz

last: Hande


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

overall_design: To confirm the maturation of LTi cells with the upregulation of RORγt expression, we performed Bulk-RNA seq on LTi progenitor cells sorted from the E14.5 fetal liver based on their levels of RORγt expression. Additionally, we further subdivided the RORγt high population based on the expression of CD127 and MHC class II to confirm their heterogeneity


title: A sRNA ncBCG427 of Bacillus Calmette-Guérin enhances intracellular bacterial survival likely through inhibition of inflammatory response and apoptosis

city: Wuhan

first: Kailun

last: Zhang

address: No. 1 Shizishan Road

country: China

institute: Huazhong Agricultural University

summary: We use high-throughput sequencing to validate and screen the target genes predicted earlier, and conduct inflammation and apoptosis related experiments based on the screened genes.

sample_organism: Mycobacterium tuberculosis variant bovis BCG

overall_design: We constructed an overexpression strain of ncBCG427 and performed high-throughput sequencing with an vector strain to obtain differentially expressed genes

first: Zejin

last: Du

first: Chao

last: Wang

first: Zijian


title: BRD4-mediated ER membrane contact creates functionally distinct mitochondrial subtypes

city: Ann Arbor

first: Mats

last: Ljungman

state: Michigan

address: NCRC, B520 Room 1346 2800 Plymouth Rd.

institute: University of Michigan

summary: Inter-organellar communication is critical for cellular metabolic homeostasis. One of the most abundant inter-organellar interactions are those at the endoplasmic reticulum and mitochondria contact sites (ERMCS). However, a detailed understanding of the mechanisms governing ERMCS regulation and their roles in cellular metabolism are limited by a lack of tools that permit temporal induction and reversal. Through unbiased screening approaches, we identified fedratinib, an FDA-approved drug, that dramatically increases ERMCS abundance by inhibiting the epigenetic modifier BRD4. Fedratinib rapidly and reversibly modulates mitochondrial and ER morphology and alters metabolic homeostasis. Moreover, ERMCS modulation depends on mitochondria electron transport chain complex III function. Comparison of fedratinib activity to other reported inducers of ERMCS revealed common mechanisms of induction and function, providing clarity and union to a growing body of experimental observations. In total, our results uncovered a novel epigenetic signaling pathway and an endogenous metabolic regulator that connects ERMCS and cellular metabolism.

overall_design: The changes in the nascent transcriptome were investigated using BrU-seq when SW480 cells were exposed to 1uM of Fedratinib for 30 min (2 replicates) or 2 hour (2 replicates) when compared to a control condition (cells treated with DMSO for the same treatment duration, 2 replicates for the 30 min DMSO control, 1 replicate for the 2 hour DMSO control).

first: Brandon

last: Chen

first: Drew

last: Stark

first: Pankaj

last: Jadhav

first: Theophilus

last: Lynn-Nguyen

first: Benjamin

last: Halligan

first: Nicholas

last: Rossiter

first: Nicole

last: Sidoni

first: Myunsun

last: Shin

first: Joao

last: Paolo

first: Matthew

last: Chang

first: Sergei

last: Koshkin

first: Imhoi

last: Koo

first: Sanjana

last: Eyunni

first: Paolo

last: Ronchi

first: Michelle

last: Paulsen

first: Pietro

last: Morlacchi

first: David

last: Hanna

first: Jason

last: Lin

last: Guerra

last: Pagliarini

first: Ruma

last: Banerjee

first: Abhijit

last: Parolia

first: Andrew

last: Patterson

first: Joseph

last: Mancias

first: Shyamal

last: Mosalaganti

first: Jonathan

last: Sexton

first: Tito

last: Calí

first: Costas

last: Lyssiotis

first: Yatrik

last: Shah


title: Therapeutic reactivation of hippocampal progenitors reverses cognition decline in progressive brain demyelination

city: Winnipeg

first: Soheila

last: Karimi

state: Manitoba

address: 745 Bannatyne Avenue

department: Physiology and Pathophysiology

country: Canada

institute: University of Manitoba

summary: Chronic brain demyelination and neurodegeneration are pathological hallmarks of progressive multiple sclerosis (MS) that underlie cognitive impairments. Neural precursor cells (NPCs) that reside in the hippocampus support cognition through adult neurogenesis. However, with MS chronicity, hippocampal neurogenesis declines that results in memory and learning impairments. Currently, the underlying mechanisms that drive NPC senescence in chronic MS are largely unknown. Here, we have linked downregulation of Neuregulin-1beta 1 (Nrg-1β1) to hippocampal neurodegeneration, neurogenic decline and memory impairment in mice with chronic brain demyelination. Nrg-1β1 is a key factor for neural differentiation that we previously reported its downregulation in chronic human MS lesions. Here, extensive in vivo and in vitro characterizations revealed that therapeutic restoration of Nrg-1β1 can reactivate NPCs and foster hippocampal repair by neurogenesis, synapse reassembly and remyelination that reverses memory impairments. Transcriptomics of NPC progenies confirmed upregulation of genes associated with myelination, synaptic resilience, and cellular homeostasis, underscoring the potential of Nrg-1β1 in activating regenerative mechanisms within the chronically demyelinated hippocampus. Moreover, in comparison with Siponimod, a leading disease modifying therapy for secondary progressive MS, Nrg1β1 treatment achieved multifaceted and greater reparative effects. These new findings introduce Nrg1β1 as a disease relevant candidate with promising therapeutic potential for progressive MS.

overall_design: The samples are hip-NPC (GFP+)  isolated from hippocampus of mice using magnetic-activated cell sorting (MACS). Each sample is the result of one mouse brain. The treatment groups include: 1- Cuprizone for 10 weeks + 4 weeks of spontaneous recovery period (Vehicle) (0.1% BSA in saline) treatment. 2-  Cuprizone for 10 weeks + 4 weeks of recovery period and Neuregulin 1 beta 1 (60µg/kg/day) treatment.


title: Selective Sensitivity of Ph-like B-ALL to BRG1 Inhibition Identifies a Therapeutic Vulnerability

city: Loma Linda

first: V. S. S. Abhinav

last: Ayyadevara

address: 11085 Campus St

department: Basic Sciences

institute: Loma Linda University

summary: Despite therapeutic advances, high-risk subtypes of B-cell acute lymphoblastic leukemia (B-ALL) such as Philadelphia chromosome-like (Ph-like) and KMT2A-rearranged (KMT2A-R) remain a formidable clinical challenge. BRG1 (gene name SMARCA4), the ATPase subunit of the SWI/SNF chromatin-remodeling complex, has been extensively studied in solid tumors, where inactivating mutations are linked to aggressive disease and poor prognosis. Although BRG1 is known to be essential for early B cell development, its role in B-ALL remains poorly understood. Therefore, we investigated the therapeutic relevance of BRG1 in high-risk B-ALL. Meta-analysis of gene expression data revealed that BRG1-inactivating mutations are exceedingly rare (0.35%) in B-ALL, suggesting that intact BRG1 function may be critical for leukemogenesis. Subtype-specific analyses revealed that elevated BRG1 expression is associated with significantly shorter overall survival in children with Ph-like B-ALL, while the opposite trend was observed in KMT2A-R B-ALL. We confirmed higher BRG1 expressions in Ph-like compared to KMT2A-R B-ALL via gene expression analysis, RT-PCR, and Western blotting.  The pharmacologic inhibition of BRG1 using two selective inhibitors, BRM014 and FHD-286, revealed marked sensitivity in Ph-like B-ALL cell lines, whereas KMT2A-R B-ALL was resistant. Mechanistically, we found that BRG1 inhibition results in cell cycle arrest via downregulation of cell cycle regulators (CCND3, CDK4, CDK6, E2F1, and MYC) and upregulation of the cell cycle inhibitor CDKN1B (p27). Importantly, treatment with FHD-286 significantly prolonged the survival of NSG mice engrafted with Ph-like B-ALL cells.  Taken together, these findings establish BRG1 as a critical, subtype-specific dependency in Ph-like B-ALL and demonstrate that its pharmacologic inhibition effectively suppresses leukemic cell proliferation through induction of cell cycle arrest. The pronounced in vitro sensitivity and improved in vivo survival upon BRG1 inhibition provide compelling preclinical evidence for its therapeutic targeting. These results support the advancement of BRG1-directed strategies as a viable treatment approach for patients with Ph-like B-ALL, with the potential to improve outcomes in this high-risk population.

overall_design: The human CRLF2-rearranged Ph-like B-ALL (MUTZ5 and MHH-CALL4) and the KMT2A-rearranged B-ALL (HB11;19 and RS4;11) cell lines were treated with vehicle control or 100nM FHD-286 (BRG1/BRM inhibitor) for 24 hours in a cell culture plate in vitro

first: Shikha

last: Gaur

first: Shreya

last: Patil

first: Ashley

last: Paik

first: Ria

last: Perencsik

first: Monika

last: Toma

first: Gerald

last: Wertheim

first: Huimin

last: Geng

first: Tomasz

last: Skorski

first: Srividya

last: Swaminathan

first: Christian

last: Hurtz


title: The long-term in vitro co-exposure of polyethylene terephthalate (PET) nanoplastics and cigarette smoke condensate exacerbates the induction of carcinogenic traits

city: Bellaterra

first: Alba

last: Hernández

state: Barcelona

address: Campus UAB, s/n

department: Genetics and Microbiology

country: Spain

institute: Universitat Autònoma de Barcelona

summary: This study examines the long-term impact of polyethylene terephthalate nanoplastics (PET-NPLs) and cigarette smoke condensate (CSC) on human lung BEAS-2B cells, focusing on key biological hallmarks of carcinogenesis. True-to-life PET-NPLs were generated from plastic water bottles and characterized to simulate environmental exposure conditions; a comprehensive battery of assays was employed to assess genotoxicity, cellular transformation, and invasiveness. It was observed that, compared to passage control and individual exposures, co-exposure to PET-NPLs and CSC exacerbates oxidative stress, genotoxicity, and tumorigenic transformation, as evidenced by increased DNA damage, colony formation in soft agar, and enhanced cell migration and invasion. Transcriptomic analysis revealed a shift in cellular stress regulation including the upregulation of stress-response genes, including SLC7A11, NQO1, and HSPA1A, which are linked to oxidative stress adaptation and tumor survival. At the same time, key tumor-suppressor genes, such as GJA1, LOX, and FN1, were significantly downregulated, promoting cellular transformation and invasiveness. These results provide compelling evidence that the combination of PET-NPLs and CSC enhances carcinogenic traits through oxidative stress, genomic instability, and disruption of tumor-suppressive pathways. This study underscores the importance of evaluating the synergistic effects of combined environmental exposures and their implications for human health.

overall_design:
Previously treated BEAS-2B (30 weeks of continuos PET treatment; PTP) were treated with cigarette smoke condensate (CSC), PET or the combination of both (CSC+PET) for 4 weeks. There were 4 biological replicates for each condition.
Biomarkers of carcinogenesis were evaluated and Differenttially Expressed Genes were determined comparing coexposed samples to single-exposed samples.
Single-exposed samples encompass samples re-analysed from series GSE291738 (the GSMs codes GSM8841465 GSM8841466 GSM8841467 GSM8841468 re-analysed from GSE291738).

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

last: Morataya-Reyes

first: Aliro

last: Villacorta

first: Javier

last: Gutiérrez-García

first: Raquel

last: Egea

first: Joan

last: Martín-Pérez

first: Irene

last: Barguilla

first: Ricard

last: Marcos


title: Analysis of cellular and exosomal RNAs in AC16 cells regulated by hypertrophic cardiomyocyte

city: Chang Chun

first: Xin

last: Hu

address: 2699 Qianjin road,china

institute: Jilin university

summary: Cardiovascular diseases (CVDs) and cancer are among the most serious life-threatening diseases with very high morbidity and mortality rates. An increasing number of clinical studies have shown that cardiovascular disease is strongly associated with an increased risk of cancer and can contribute to cancer development, but the mechanisms associated with this need to be further explored in depth. Exosomes play an important role in promoting the development of cancer, and breast cancer is the most prevalent cancer among women. In the present study, we showed by in vivo experiments that exosomes from hypertrophic cardiomyocytes significantly promote breast cancer progression. In order to explore the mechanism by which hypertrophic cardiomyocytes promote the progression of breast cancer, we conducted whole transcriptome sequencing of exosomes and cells from normal cardiomyocytes and hypertrophic cardiomyocytes. Interestingly, the majority of miRNAs were downregulated in the exosomes of hypertrophic cardiomyocytes. In the downregulated miRNAs within the exosomes of hypertrophic cardiomyocytes, a consistent sequence GGCXGAGG was identified. We found that hnRNPQ regulates exosomal sorting of miR-10400-3p and several other miRNAs. Based on this, we validated the expression levels of plasma exosomal miRNAs in patients with myocardial hypertrophy using clinical data and patient samples, providing predictive markers for cancer progression in myocardial hypertrophy patients. Our findings suggest that hypertrophic cardiomyocytes regulate the expression of the RNA-binding protein hnRNPQ, which affects the levels of exosomal miRNAs and plays a key role in promoting the development of breast cancer.

overall_design: To find miRNAs regulated by hypertrophic cardiomyocytes in exosomes and to find the regulatory mechanism of miRNAs. We performeda whole transcriptome sequencing and also analysed differentially expressed miRNAs in exosomes of hypertrophic cardiomyocytes, found functional consensus sequences of differentially expressed miRNAs, and found RNA-binding proteins that can bind to miRNAs, thus further elucidating the mechanism.


title: Aberrant and Ectopic Cell Populations of the Fibrotic Front of Restrictive Allograft Syndrome after Lung Transplantation

first: Jonas

last: Schupp

summary: Single-nuclei RNA-sequencing (snRNA-seq) using the 10x Genomics Flex technology was performed in peripheral lung tissues from 15 RAS patients undergoing lung re-transplantation, and from 9 healthy control lungs.

overall_design: Lung tissue from 15 RAS patients vs 9 control lungs

first: Jens

last: Gottlieb

first: Lena

middle: M

last: Leiber

first: Danny

middle: D

last: Jonigk


title: Cord-derived iNKT cells are enriched with human NKT10 and exert the immunosuppressive function through the interaction with NRP1 [scMultiomics-seq]

city: Houston

first: Jin Seon

last: Im

state: Texas

address: 7455 Fannin St

department: HBM

institute: MD Anderson Cancer Center

summary: Invariant Natural Killer T (iNKT) cells are a unique subset of T lymphocytes that recognize glycolipid antigens presented by the non-polymorphic MHC class I-like molecule CD1d through a semi-invariant T cell antigen receptor. In mice, this receptor consists of the invariant Vα14Ja18 (TRAV11+TRAJ18+) chain paired with Vβ8, Vβ7, or Vβ2, while in humans, it comprises Vα24Ja18 (TRAV10+TRAJ18+) paired with Vβ11. Upon activation, iNKT cells modulate adaptive immunity by promoting either immune suppression or inflammation through the production of Th1- and Th2-type cytokines. They also enhance adaptive T and B cell responses via the CD40-CD40L feedback loop with antigen-presenting dendritic cells (DCs). iNKT cells exhibit phenotypic and functional heterogeneity, with subsets including CD4+ and CD4- populations, as well as functionally distinct NKT1 (Th1), NKT2 (Th2), NKT10 (Th10), and NKT17 (Th17) cells. The developmental pathways and immunological roles of murine iNKT cells are well characterized, highlighting their functional plasticity in immune modulation. The NKT10 subset, in particular, has been studied in various murine models and demonstrated a regulatory function within CD4+ iNKT cells. These cells are enriched in specific NKT10 signature markers, including IL-10, NRP1, and PD-1, which define their immunoregulatory properties. Despite these findings in mice, the phenotype and function of IL-10-producing human iNKT cells remain poorly characterized, and their regulatory role in human diseases is not well understood. Here, we aim to characterize human NKT10 cells derived from cord blood iNKT cells and explore their therapeutic potential in bone marrow transplantation.

overall_design: The freshly-expanded adult and cord-derived iNKT cells were stimulated by αGalCer-pulsed allogeneic dendritic cells for 24 hours and stained for CD3 and iNKTCR. Live iNKT cells were then sorted using BD FACSAria II Cell Sorter and submitted for single cells RNAseq analysis.


title: Optimization of in vitro production of human satellite cells for skeletal muscle cell therapy

city: Boston

first: Yannis

last: Djeffal

state: Massachusetts

address: 60 Fenwood road

department: Pathology/Genetics

institute: Brigham and Women’s Hospital/Harvard Medical School

summary: We established new iPSC-derived skeletal muscle progenitors culture models, studied their development and their engraftment in rodents.

sample_organism:
Homo sapiens
Mus musculus

platform_organism:
Homo sapiens
Mus musculus

overall_design: We collected different time points of human cell cultures in vitro and engrafted in rodents in vivo. We performed single-cell and single-nuclei RNA sequencing using the 10X Chromium v3.1 platform.

first: Djeffal

last: Yannis

first: Pourquie

last: Olivier


title: Wogonin precondition of MSCs improved their therapeutic efficiency on the colitis through promoting glycolysis

city: guangzhou

first: Wu

middle: Meng

last: ye

state: Guangdong

address: Guangzhou Yuexiu

department: The Biotherapy Center,

institute: the Third Affiliated Hospital, Sun Yat-Sen University

summary: In order to clarify the underlying mechanism of wogonin improving the therapeutic effect of MSCs in DSS-induced colitis

overall_design: We then performed gene expression profiling analysis using data obtained from RNA-seq of MSC treatment with the presence and obsence of wogonin for 24h, and Comparative gene expression profiling analysis of RNA-seq data between them.

first: Yanwen

last: Peng

first: Mengye

last: Wu

first: Cuiping

last: Li

first: Xue

last: Zhou


title: Analysis of cellular and exosomal miRNAs in AC16 cells regulated by hypertrophic cardiomyocyte

type: Non-coding RNA profiling by high throughput sequencing

overall_design: To find miRNAs regulated by hypertrophic cardiomyocytes in exosomes and to find the regulatory mechanism of miRNAs. We performed a whole transcriptome sequencing of exosomes and also analysed differentially expressed miRNAs in exosomes of hypertrophic cardiomyocytes, found functional consensus sequences of differentially expressed miRNAs, and found RNA-binding proteins that can bind to miRNAs, thus further elucidating the mechanism.


title: RNA-seq analysis of human NSCLC cell lines treated with 9α,11α-dihydroxy-kaurenoic acid (AL-X)

status: Public on Mar 23 2026

city: Taichung

first: Po-Chen

last: Chu

address: No. 100, Sec. 1, Jingmao Rd., Beitun Dist.

country: Taiwan

institute: China Medical University

summary: Non-small cell lung cancer (NSCLC) remains a leading cause of cancer-related mortality worldwide. In this study, we performed bulk RNA sequencing to investigate the transcriptomic effects of 9α,11α-dihydroxy-kaurenoic acid (9α,11αOH-KA, also referred to as AL-X) in human NSCLC cells. A549, HCC827, and H1975 cell lines were treated with 10 μg/mL 9α,11αOH-KA or vehicle (DMSO) for 48 hours. Total RNA was extracted and subjected to paired-end sequencing using the Illumina platform. This dataset provides a comprehensive resource for understanding the molecular mechanisms underlying mitochondrial dysfunction and anti-cancer effects induced by 9α,11αOH-KA in NSCLC.

overall_design: Three human NSCLC cell lines (A549, HCC827, and H1975) were treated with DMSO (control) or 10 μg/mL 9α,11αOH-KA for 48 hours. Total RNA was extracted and used for library preparation and paired-end RNA sequencing (Illumina platform).

first: Yu-Chi

last: Liu


title: Deciphering lineage decision of hematopoietic stem cells at homeostasis and aging

city: Chengdu

first: Yujun

last: Deng

address: No. 17, Section 3, Renmin South Road, Chengdu

institute: Sichuan University

summary: To revealed the mechanism of long-term hematopoietic stem cells (LT-HSCs) lineage decision and bias during aging, we applied scRNA sequencing with three sub-clusters within the compartment in different age groups, namely CD150hiSca1hi LT-HSCs, CD150hiSca1lo LT-HSCs and CD150lo LT-HSCs. These three LT-HSC subsets encompass a spectrum of lineage specification and commitment cell states, which were further segregated into 6 different clusters. Characterization of the self-renewal capacity and lineage potential of the quiescence HSC subpopulation by transplantation assays revealed the identity of bona fide HSC (Meg3+-HSC), which expanded dramatically started at middle-age, with dynamic transcriptional activities associated with protein modification and platelets activation.

overall_design: For 10x scRNA-seq or CITE-seq, CD150hi Sca1hi, CD150hi Sca1lo, and CD150lo LT-HSC from mice of different ages were sorted by using FACS AriaTM III sorter.

first: Ni

last: Wei

first: Huiwen

last: Zhan

first: Min

first: Pengbo

last: Guan

first: Yusi

last: Xie

first: Lunzhi

last: Dai

first: Hongbo

first: Huiyuan

last: Zhang


title: Leveraging experimental evolution to extract predictive collateral drug response signatures in Ewings Sarcoma

city: Cleveland

first: Kristi

last: Lin-Rahardja

state: OH

address: 10900 Euclid Ave

department: Systems Biology & Bioinformatics

institute: Case Western Reserve University

summary: Therapeutic options for patients with relapsed or refractory Ewings sarcoma (EWS) remain limited. Collateral sensitivity, where resistance to one drug confers sensitivity to another, could be leveraged to optimize chemotherapy for EWS. Gene expression signatures that predict collateral sensitivity states can be used to guide treatment selection in an evolution-informed manner. To generate such biomarkers, we experimentally evolved resistance to first-line EWS chemotherapy in independent replicates of an EWS cell line, all originating from the same ancestor population. Throughout, we measured collateral responses across a panel of anticancer drugs and quantified transcriptomic changes. Collateral drug responses varied across replicate evolutionary trajectories, but convergent states of collateral sensitivity emerged across different replicates at different times. By associating these convergent phenotypes with gene expression patterns, we derived a library of predictive signatures for numerous drugs. These signatures accurately distinguished states of collaterally sensitivity from states of collateral resistance within our dataset, irrespective of a replicate's evolutionary history. Our findings demonstrate that gene expression signatures can predict collateral sensitivity in EWS, providing a foundation for personalized therapeutic strategies. This approach also establishes a generalizable workflow for developing predictive biomarkers to guide chemotherapy selection in patients with rare diseases that lack reliable second-line chemotherapy regimens.

overall_design: From one treatment-naïve cell line (WT), establish 10 separate replicates (R1-R10). R1-7 will be treated with first-line chemotherapy for EWS (alternating doses of vincristine-doxorubicin-cyclophosphamide, or VDC, and etoposide-cyclophosphamide, or EC). Treatment will occur for 5 full cycles/10 total treatments, where each cycle is numbered with the treatment (time 1 = VDC1, time 2 = EC1, time 3 = VDC2, time 4 = EC2, etc.). R8-10 will be treated with DMSO and labeled with the same time point nomenclature. At the end of every time point, each replicate will be sampled for RNA-seq and drug screening against 48 other agents as well as VDC or EC, depending on which treatment the replicate had just received.

last: Lin

first: Ethan

last: Canavan

first: Jacob

middle: G

last: Scott


title: RNA N6-Methyladenosine (m6A) regulates cell cycle progression in Diffuse Midline Glioma (DMG) and confers sensitivity to FTO inhibition

city: Sydney

first: Samuel

middle: Ernest

last: Ross

state: NSW

address: The University of Sydney

country: Australia

institute: The University of Sydney

summary: The epitranscriptome has not previously been evaluated in DMG. Given the pivotal role of m6A in normal OPC biology, investigating its dysregulation in DMG could uncover new therapeutic options and improve our understanding of the disease's underlying mechanisms. Here, for the first time, we perform direct RNA-sequencing on patient-derived DMG cultures to generate transcript and base-resolution m6A landscapes of DMG. Furthermore, we interrogate the therapeutic benefits of  the Fat mass and obesity associated (FTO) player inhibitor FB23-2 in DMG using direct RNA sequencing and RNA sequencing

overall_design: To investigate the m6A landscape of DMG, we have peformed direct RNA-sequencing on normal patient cells, SU-DIPGXIII, SU-DIPGXVII, and FB23-2 treated SU-DIPGXVIII cultures. Additionally, to investigate the effects of FTO inhibition, we have peformed RNA sequencing on SU-DIPGXIII, SU-DIPGXVII, and HSJD-DIPG007 cultures after 24 hour treatments with DMSO or FB23-2 at ~IC50 concentration.

middle: E


title: The mechanism of action of lotus node charcoal carbon dots in improving ulcerative colitis

city: Nanjing

first: po

last: hu

state: jiangsu

address: 栖霞区 南京中医药大学 B3-F106（栖霞仙林校区）

institute: 南京中医药大学

summary: Ulcerative colitis is an inflammatory bowel disease with a complex etiology, primarily involving the colonic mucosa and submucosa, with the core pathological features being diarrhea, abdominal pain, and hematochezia. Current Western medical treatments mainly include aminosalicylates, corticosteroids, and immunosuppressants, which are associated with significant side effects and a high risk of recurrence. In traditional Chinese medicine, lotus node charcoal has been used for its hemostatic and anti-inflammatory effects to alleviate symptoms such as hematochezia, abdominal pain, and tenesmus in UC. However, the material basis underlying these effects has not yet been elucidated, and the emergence of carbon dots offers a scientific explanation. Our work integrates traditional Chinese medicine with modern nanotechnology, providing a scientific foundation for studying the material basis of the "hemostatic effect of charcoal-processed herbs" and offering a novel approach for the treatment of ulcerative colitis.

overall_design: The submission includes colon tissue samples from mice assigned to different experimental groups.Experimental conditions include blank, DSS-induced Ulcerative colitis and lotus node charcoal carbon dots treatment.Biological replicates are included for all groups.

first: Yijia

last: Liang


title: Dynamic Phenotyping Reveals Highly Personalized, Integrated Host-Tumor Crosstalk During Exercise in Cancer Patients

city: Los Angeles

first: Brandon

last: Tsai

state: California

address: 405 Hilgard Ave

institute: University of California, Los Angeles

summary: How exercise therapy modulates the host systemic environment to regulate tumor evolution in humans is not known. We performed personalized, multiparametric, longitudinal profiling before, during, and after short-term endurance exercise in 13 patients with solid tumors in a preoperative “window” study. Time-series analyses revealed hundreds of host molecular changes in the plasma metabolome and proteome and gut microbiome involved in a diverse-array of biological processes. Host systemic environmental changes were paralleled by modulation of core tumor gene expression pathways notably tumor cell cycle regulation, stress response, and metabolism. Integrative network analyses revealed the complexity of the host – tumor interaction under exercise regulation, elucidating novel mechanistic insights. Variability at baseline and during intervention highlighted highly personalized responses to uniform exercise therapy. Our study provides an example of how generation of a longitudinal high-definition dataset provides a framework for interrogation of the integrative, host-tissue response to exercise in clinical populations.

overall_design:
To characterize exercise-related alterations in the systemic host environment, we profiled changes in the gut microbiome. Stool was sampled weekly and returned via a pre-paid courier service. Eight patients consented to provide serial stool samples. Stool was profiled using 16S-sequencing.

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

first: Lee

last: Jones


title: Plasma cfDNA and Peripheral Blood gDNA Provide Complementary Information for Molecular Monitoring in Myeloproliferative Neoplasms

city: Shanghai

first: Xiaotong

last: Ma

address: No. 12, middle Urumqi Road

department: Department of Laboratory Medicine

institute: Huashan hospital

type: Methylation profiling by genome tiling array

summary: This project examines the complementary roles of plasma cell-free DNA (cfDNA) and peripheral blood genomic DNA (gDNA) for molecular monitoring in myeloproliferative neoplasms (MPNs).

overall_design: We systematically demonstrate that cfDNA and gDNA originate from biologically distinct pools and provide complementary clinical value. Utilizing multi-modal validation (methylation deconvolution, xenograft models, and two clinical cohorts), we show cfDNA is enriched for marrow-derived DNA and more sensitively detects mutation burden and therapeutic resistance. In contrast, gDNA better confirms treatment response. Crucially, we identify lymphocyte percentage as a novel, routine biomarker that predicts when cfDNA offers superior sensitivity, enabling a practical framework for test selection.


title: Promoter mutagenesis and a massively parallel reporter screen of the MAPT locus identifies cis-regulatory elements and genetic variation effects

city: Huntsville

first: Jesse

middle: Nicholas

last: Cochran

state: AL

address: 601 Genome Way

institute: HudsonAlpha Institute for Biotechnology

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

overall_design: Refer to individual Series


title: Nuclear Speckle Dynamics are Controlled by Polyphosphate Inhibition of CLK Proteins

city: Sant Cugat del Vallés

last: Bru

address: Josep Trueta, s/n

department: Biomedical Sciences

institute: Universitat Internacional de Catalunya

summary: Nuclear speckles (NS) are membrane-less nuclear organelles that act as critical hubs for pre-mRNA splicing. Defects in splicing are linked to several human diseases, including cancer, Alzheimer's disease, and dystrophies. While CLK kinases regulate the mobilization of splicing factors from NS, the molecular mechanisms underlying NS assembly and dissolution remain unclear. Using an adaptation of the Biotinylation by Antibody Recognition (BAR) technique, we identified polyphosphate (polyP) as a novel and essential regulator of NS dynamics. Polyphosphate, a highly conserved polyanion composed of a chain of phosphate molecules, is involved in several functions in mammalian cells. Here, we show that polyP interacts with the NS core component SRRM2, and its depletion disrupts NS organization releasing splicing factors into the nucleoplasm. RNA-seq analysis reveals that polyP depletion increases exon exclusion, particularly in transcripts with multiple isoforms, highlighting its role in splicing regulation. Mechanistically, we demonstrate that polyP acts as a physiological inhibitor of CLK3 kinase, preventing the phosphorylation of SR proteins and thereby maintaining NS stability. Our findings not only expand our understanding of NS biology but also provide new insights into the polyP involvement in splicing-related diseases.

overall_design: This study investigates the transcriptomic changes in HEK293T cells under two different experimental setups: overexpression and knockdown. In the first group, cells were transfected with either an empty pWPI plasmid (control) or pWPI vectors carrying NUDT3, PRUNE1, or CLK3 (n=4 replicates per condition). In the second group, cells were transfected with siScramble (control) or siSRRM2 (n=2 replicates per condition). All cells were harvested 48 hours post-transfection for total RNA extraction. Sequencing was performed by Macrogen using the Illumina NovaSeq 6000 platform, generating 150 bp paired-end reads with a depth of approximately 100 million reads per sample.

first: Blanca

last: Lázaro

first: Francisco

middle: J

last: Tadeo

first: Andrea

last: Rodríguez

first: Lucía

last: Ayuso-Molina

first: Joan

last: Martínez-Láinez

first: Eva

last: Quandt

first: Maribel

last: Bernard

first: Filipy

last: Borghi

first: Adolfo

last: Saiardi

first: Jonàs

last: Juan-Mateu

first: Javier

last: Jiménez

first: Josep

last: Clotet


title: CD69 regulates the tissue dynamics of epigenetically imprinted memory CD4+ T cells [scRNA-seq]

city: chiba city

first: Masahiro

last: Kiuchi

state: chiba

address: cyuoku inohana1-8-1

institute: Chiba univercity

summary: Tissue-resident memory T (TRM) cells reside in non-lymphoid tissues and provide the first line of defense against pathogens. A subset of TRM cells can egress from non-lymphoid tissues into the circulation. However, the functional consequences and the extent of epigenetic imprinting in recirculating TRM cells remain unknown. We herein demonstrate that in CD4+ TRM cells, the CD69-S1PR1 axis controls tissue residency, and that interrupting this axis results in ablation of lung CD4+ TRM cells. A subpopulation of CD69+CD4+ TRM cells re-entered circulation via lymphatic vessels, where they epigenetically maintained the characteristics of TRM cells in both mice and humans. Circulating Ex-lung-TRM cells in mice caused enhanced skin inflammation compared to circulating memory cells. Furthermore, we identified GPR183 and CD161 as potential markers of Ex-TRM in human PBMC. In chronic inflammatory diseases, the transposition of allergic inflammation to multiple tissues may therefore occur via recirculation of tissue-imprinted memory CD4+ T cells.

overall_design: This study aimed to characterize the transcriptional profiles of lung tissue-resident memory CD4⁺ T (TRM) cells and circulating CD4⁺ T cells using an antigen-specific adoptive transfer model. OVA-specific effector Th2 cells were generated in vitro from TCR-transgenic mice and intravenously transferred into syngeneic recipient mice. Following intranasal OVA challenge, lung CD4⁺ T cells were isolated and separated into tissue-resident (CD45(iv)⁻) and circulating (CD45(iv)⁺) populations using intravascular anti-CD45 staining. Single-cell RNA sequencing (scRNA-seq) was performed to define transcriptional signatures associated with tissue residency and circulation.

first: Rui

last: Hirasawa

first: Chiaki

last: Iwamura

first: Hiroyuki

last: Yagyu

first: Takahisa

last: Hishiya

first: Norie

last: Hamaguchi

first: Atsushi

last: Sasaki

first: Kohei

last: Kakinuma

first: Kanae

last: Ohishi

first: Akane

last: Kurosugi

last: Nemoto

first: Kota

last: Kokubo

first: Takuto

last: Hiramoto

first: Tomohisa

last: Iinuma

first: Syuji

last: Yonekura

last: Onodera

first: Motoko

middle: Y

last: Kimura

first: Shinichiro

last: Motohashi

first: Damon

last: Tumes

first: Toyoyuki

last: Hanazawa

first: Toshinori

last: Nakayama

first: Seiji

last: Ohtori

first: Kiyoshi

last: Hirahara


title: CD69 regulates the tissue dynamics of epigenetically imprinted memory CD4+ T cells [scATAC-seq]

first: Masahiro

last: Kiuchi

overall_design: Peripheral blood mononuclear cells (PBMCs) and nasal polyp-derived CD4 memory T cells were obtained from patients with eosinophilic chronic rhinosinusitis (ECRS). Single-cell ATAC-seq (scATAC-seq) was performed to characterize chromatin accessibility profiles of circulating and tissue-resident CD4 memory T cells. Comparative analyses were conducted between PBMC-derived and polyp-derived CD4 memory T cells.

first: Rui

last: Hirasawa

first: Chiaki

last: Iwamura

first: Hiroyuki

last: Yagyu

first: Takahisa

last: Hishiya

last: Hamaguchi

last: Sasaki


title: H3K18 lactylation promotes cell proliferation in T-Cell acute lymphoblastic leukemia

city: Nantong

first: Lingling

last: Feng

address: No. 399, Shiji Avenue

institute: Affiliated Maternity and Child Health Care Hospital of Nantong University

summary:
Running title: H3K18lac promotes T-ALL cell proliferation
To identify potential target genes regulated by H3K18lac in T-ALL cell proliferation, we performed RNA-sequencing (RNA-seq) analysis on LDHA-knockdown J.gamma1 and Jurkat cells

overall_design: RNA-seq profiling of negative control and LDHA-knockdown J.gamma1 and Jurkat cells derived from shcontorl or shLDHA.

first: Xia

last: Jin

first: Juan

last: Zhang

first: Zong

last: Zhai

first: Xiaohua

first: Yi

last: Wang


title: Dynamic Phenotyping Reveals Highly Personalized, Integrated Host-Tumor Crosstalk During Exercise in Cancer Patients [proteomics data]

first: Brandon

last: Tsai

summary: How exercise therapy modulates the host systemic environment to regulate tumor evolution in humans is not known. We performed personalized, multiparametric, longitudinal profiling before, during, and after short-term endurance exercise in 13 patients with solid tumors in a preoperative “window” study.

overall_design: Our study included multiparametric, high frequency profiling of lifestyle and physiological parameters, weekly sampling of the metabolome, proteome, and gut microbiome, and whole tumor transcriptomics before, during, and after intervention with highly structured and uniform endurance exercise.

first: Tsai

last: Brandon

first: Jones

last: Lee


title: CD69 regulates the tissue dynamics of epigenetically imprinted memory CD4+ T cells [RNA-seq_ATAC-seq]

overall_design: Effector Th2 cells derived from OT-II creERT2 or DO11.10 TCR transgenic mice were transferred into OVA-sensitized C57BL/6 (Ly5.2) or BALB/c-nu/nu recipient mice to establish tissue-resident memory Th2 (TRM) populations. In the first experiment, donor-derived CD45.1⁺ effector Th2 cells were traced following tamoxifen-induced recombination, and on day 49, circulating ex-TRM cells were isolated from peripheral blood, while tissue TRM cells were sorted from lungs based on CD69 and congenic markers. In the second experiment, lung TRM and TCIRC cells from DO11.10 mice were secondarily transferred into naïve BALB/c-nu/nu recipients and analyzed on day 71 after OVA rechallenge. Approximately 3,000–50,000 sorted cells from each subset were subjected to ATAC-seq to assess chromatin accessibility or to RNA-seq to profile gene expression, allowing comparison of epigenetic and transcriptional features among tissue-resident, circulating, and endogenous memory CD4⁺ T-cell populations.

first: Norie

first: Atsushi

first: Kohei

last: Kakinuma

first: Kanae

last: Ohishi

first: Akane

last: Kurosugi

last: Nemoto

first: Kota

last: Kokubo

first: Takuto

last: Hiramoto

first: Tomohisa

last: Iinuma

first: Syuji

last: Yonekura

last: Onodera

first: Motoko

last: Kimura

first: Shinichiro

last: Motohashi

first: Damon

last: Tumes

first: Toyoyuki

last: Hanazawa

first: Toshinori

last: Nakayama

last: Ohtori


title: Nag3  regulates the development of Penicillium oxalicum fungi and the expression of cellulolytic genes

city: Qingdao

first: Panpan

last: Zhang

address: No. 72, Coastal Road, Aoshanwei Sub-district, Jimo District, Qingdao City, Shandong Province

institute: ShanDong University

summary: The goals of this study are to compare different gene expressions for Penicillium oxalicum wild type strain (WT) and Nag3 deletion strain (DNag3) under conditions of  2% glucose,2% N-GlcNAc  and 1% bran + 1% microcrystalline cellulose as carbon source.

overall_design: Examination of differential gene expressions by digital gene expression tag profiling in Penicillium oxalicum wild type strain and nag3 deletion mutant strains in 24h in modifeid Mendal’s medium with  2% glucose,2% N-GlcNAc  or 1% bran + 1% microcrystalline cellulose as carbon source. Three replicates were included for each samples.

first: Yuqi

last: Qin


title: HIF-1α and HIF-2α transcription factors differentially regulate lung alveolar macrophage function

city: Madrid

first: Irene

last: Adan-Barrientos

address: Melchor Fernandez Almagro 3

institute: CNIC

summary: Alveolar Macrophages (AMs) reside in the alveoli, therefore maintaining an active degradation of hypoxia-inducible transcription factors (HIF) mediated by Von Hippel-Lindau protein (pVHL). We previously found that Vhl-deficient AMs are immature and functionally impaired. Here we investigated the specific contribution of HIF-1α and HIF-2α isoforms to the regulation of the AM function. Our work demonstrates that in Vhl-deficient macrophages, both HIF-1α and HIF-2α contribute to AM defective self-renewal, while HIF-2α plays a central role in regulating the impaired AM maturation associated with pVHL loss. HIF-1α promotes a glycolytic shift in alveolar macrophages, while HIF-2α hinders lipid oxidation and surfactant clearance. Thus, HIF-2α raises as a selective critical factor restraining the therapeutic potential of AMs to degrade surfactant excess in mice that have developed pulmonary alveolar proteinosis (PAP). Overall, regulation of both HIF-1α and HIF-2α isoforms is required for an optimal AM function.

overall_design: Bulk RNA-seq of alveolar macrophages isolated from CD11c∆Vhl∆Hif1a, CD11c∆Vhl∆Hif2a, CD11c∆Vhl∆Hif1a∆Hif2a mice and their respective controls. This analysis is complementary to bulk RNAseq of  alveolar macrophages isolated from CD11c∆Vhl vs controls, deposited under GSE108975

first: Elena

last: Priego

first: Ruth

last: Conde-Garrosa

first: Sarai

last: Martínez-Cano

first: Iria

last: Sánchez

first: Diego

last: Mañanes

first: Annalaura

last: Mastrangelo

first: Joaquín

last: Amores

first: Helena

last: Izquierdo

first: David

last: Sancho


title: Single-cell RNA-seq profiling of the DHT-induced androgenetic alopecia (AGA) mouse model treated with anti-DKK3 antibody

city: Incheon

first: Jong-Hyuk

last: Sung

address: 32 Songdogwahak-ro

country: South Korea

institute: Epi Biotech Co., Ltd.

summary: Androgenetic alopecia (AGA) is characterized by progressive hair follicle miniaturization and remodeling of the skin microenvironment. To investigate cellular changes associated with AGA and the effects of DKK3 blockade, we performed single-cell RNA sequencing (scRNA-seq) of dorsal skin from a DHT-induced mouse model. Three experimental groups of male C3H/HeN mice were analyzed: vehicle control, DHT-treated AGA model, and DHT-treated mice receiving anti-DKK3 neutralizing antibody. Single-cell transcriptomic profiling identified cell population changes associated with DHT exposure and their modulation by anti-DKK3 treatment. This dataset provides a single-cell atlas of dorsal skin in the AGA model and following DKK3 inhibition.

overall_design: Dorsal skin samples were collected from three groups of male C3H/HeN mice: vehicle control, DHT-treated AGA model, and DHT-treated AGA model with anti-DKK3 neutralizing antibody.

first: Minsoo

last: Noh

first: Seungchan

last: An

first: Hyunju

last: Kim

first: Mei

last: Zheng

first: In Guk

last: Park

first: Leegu

last: Song


title: A chemical inducer of ribophagy limits the toxicity of ALS-related arginine-rich peptides

first: Oscar

last: Fernandez-Capetillo

address: Fermin Caballero 56, 3D

institute: CNIO

summary: 9ORF72 intronic repeat expansions are the most frequent mutation found in Amyotrophic Lateral Sclerosis (ALS), producing toxic arginine-rich dipeptides (DPR) that disrupt RNA metabolism and trigger orphan ribosomal protein (RP) accumulation. Through a large phenotypic chemical screen, we identified “SALSa”, a novel compound that mitigates DPR toxicity. Mechanistically, SALSa acts as a chemical inducer of ribophagy that promotes RP clearance. Interestingly, this effect is unrelated to mTOR inhibition, the main regulator of autophagy. In contrast, this is due to an effect of the drug on ribosome biogenesis, which triggers a protective response to clear defective ribosomes. Accordingly, SALSa accumulates at nucleoli and perturbs the final steps of rRNA maturation. Finally, SALSa significantly extends lifespan in a Drosophila melanogaster model of C9ORF72 ALS. These findings suggest that stimulating ribophagy could be beneficial for pathologies associated to dysfunctional ribosome biogenesis, including C9ORF72 ALS.

overall_design: MCF7 cells were treated with SALSa (119) for 6 hours and compared to untreated controls. Two biological replicates (A and B) were analyzed.

first: Bartlomiej

last: Porebski

first: Vanesa

last: Lafarga

last: Férnandez-Capetillo


title: The role of retinoic acid receptor signaling in liver cells during Alcohol-associated liver disease resolution by spatial transcriptomics analysis

city: Kansas City

first: Irina

last: Tikhanovich

state: Kansas

address: 3901 Rainbow blvd

institute: University of Kansas Medical Center

summary: Abstinence is beneficial for patients with alcohol-associated liver disease (ALD), but disease resolution after alcohol cessation occurs slowly and only in a subset of patients. Mechanisms of fibrosis resolution in ALD are not yet fully understood. Previous work highlights the importance of liver niche remodeling around areas of fibrosis that involves protein and metabolite mediated cell-cell crosstalk between hepatocytes and non-parenchymal cells. We aimed to study the mechanisms of ALD resolution using spatial transcriptomics. We found that retinoic acid metabolism strongly associated with improved fibrosis resolution in a mouse model of ALD. In agreement with this finding, mice treated with RAR agonist AM580 after alcohol cessation showed improved fibrosis resolution. Spatial transcriptomics analysis of agonist treated mice and controls suggested that RAR activation dramatically altered liver niches thus promoting pro-resolving changes in liver cells.

overall_design: Mice were fed high fat Western diet and 20% alcohol in the drinking water (WDA model of ALD), mice were then placed on chow diet with plain water to assess disease resolution. 2 mice (one was treated with DMSO control and one was treated with AM580) were selected. Biopsy sample (end of WDA) and end of experiment liver sample for each mouse were  analyzed on the same Xenium slide.

first: Michael

last: Schonfeld


title: Effect of TRAP-1 and control compounds on gene expression in BxPC-3 cells

city: Palo Alto

first: Steven

last: Corsello

address: 240 Pasteur Drive

department: Stanford School of Medicine

institute: Stanford University

summary: TRAP-1 is a transcriptional activator of p53. To determine the downstream effects of TRAP-1 on gene expression, we perfromed mRNAseq on BxPC-3 cells treateted with the drug, negative controls, and positive controls.

overall_design: BxPC-3 cells were seeded into a 6-well plate (5x10^5 cells / well), cultured overnight, treated with the indicated compounds for either 2 or 4 h, and harvested with TRIzol (Invitrogen). Total RNA was extracted using the Direct-zol RNA MicroPrep kit (Zymo Research) according to the manufacturer's instructions. For sequencing library preparation, polyA-containing transcript were enriched, prepared into paired-end libraries, and sequenced on an Illumina NovaSeq using paired-end 150-bp read length by Novogene. Gene-level expression was quantified from RNA-seq using the nf-core/rnaseq pipeline (version 3.18.0). Salmon (version 1.10.3) was used to generate gene-level read counts.

first: Nick

middle: A

last: Phillips

first: Xijun

last: Zhu


title: Physiological perfusion of human vasculature reveals a YAP/TAZ-Apelin switch linking intraluminal flow to endothelial state transitions and vessel remodeling

city: Toronto

first: Jeff

last: Wrana

state: Ontario

address: 600 University Avenue

institute: Lunenfeld-Tanenbaum Research Institute


title: Dynamic Phenotyping Reveals Highly Personalized, Integrated Host-Tumor Crosstalk During Exercise in Cancer Patients [transcriptomics data]

first: Brandon

last: Tsai

overall_design:
To determine whether exercise-induced host physiological changes occurred in conjunction with reprogramming of tumor biology and the TME, we performed bulk transcriptomics on paired formalin-fixed paraffin embedded tumor samples obtained before (diagnostic biopsy) and after (surgical resection) exercise.

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

first: Lee

last: Jones


title: Physiological perfusion of human vasculature reveals a YAP/TAZ-Apelin switch linking intraluminal flow to endothelial state transitions and vessel remodeling [scRNA-seq]

summary: Vascular flow delivers nutrients and imposes hemodynamic forces that govern vessel behavior in health and disease, yet fully human systems that recapitulate and tune physiological intraluminal flow in three-dimensional (3D) tissues are lacking. We developed VIVOS (Vascularized In Vitro Organ Systems), a platform that couples perfused human vascular beds to tunable pumps, generating continuous intraluminal flow through millimetre-scale vessels and 3D tissues at physiological shear stresses and pressures. VIVOS supports integration and perfusion of diverse human organoids and tissues, including lung organoids, cerebral organoids, vascular organoids, breast spheroids, and human retinal explants, as well as enables direct measurement and control of pressure, shear stress, and perfusion-dominant compound transport over extended culture periods. By tuning intraluminal flow and applying single-cell transcriptomics, we uncover a remodeling program in which laminar shear stress acts through a YAP/TAZ-TEAD “switch” to rewire an Apelin ligand-receptor axis and bias tip-stalk endothelial states, reshaping human vascular networks and linking hemodynamic cues to cell state transitions. We further model fast-flow arteriovenous malformations (AVMs) from Hereditary Hemorrhagic Telangiectasia and show that BMP9 constrains vessel caliber and perfusion while antagonizing a VEGF-driven angiogenic program, generating flow-quantified AVM-like lesions in a fully human 3D context. Together, these findings establish VIVOS as a generalizable platform that links physiological intraluminal flow to endothelial state transitions and vessel remodeling, enabling preclinical testing and mechanistic dissection of flow-regulated vascular pathologies in perfused 3D human tissues under defined hemodynamic conditions.

overall_design: Single cell RNA sequencing of vascular beds extracted from the VIVOS platform on Day 1, Day 4 using low flow (300 RPM impeller speed), and Day 4 using high flow (900 RPM impeller speed).

first: Tiger

middle: H

last: Jian

first: Adam

last: Sivitilli

first: Yaxin

last: Guo

first: Callum

last: Stirton

first: Jessica

middle: T

last: Gosio

first: Yuko

last: Tsukahara

first: Johnny

last: Tkach

first: Suying

last: Lu

first: Amin

last: Yarmand

first: Maria

last: Mangos

first: Rod

last: Bremner

first: Jeffrey

middle: L

first: Liliana

last: Attisano

first: Laurence

last: Pelletier


title: WTAP tetramer ensures m⁶A writer assembly and faithful mitosis

city: Anhui

first: shan

last: zhang

address: No. 443, Huangshan Road

institute: University of Science and Technology of China

summary: The m6A methyltransferase complex (“writer”) regulates mRNA stability and translation, but how its assembly is orchestrated remains incompletely understood. Wilms’ tumor 1-associating protein (WTAP) is a conserved regulatory subunit essential for m⁶A deposition and cell proliferation, yet its structural organization and mechanistic contributions remain elusive.Our live-cell imaging demonstrates that WTAP is required for accurate chromosome segregation, and MeRIP-seq analysis identifies WTAP-dependent m⁶A regulation as a critical determinant sustaining the expression of mitotic regulators, including KIF20A. Together, our study defines a tetrameric scaffold function for WTAP that is essential for writer complex integrity and highlights its pivotal role in linking m⁶A methylation to cell cycle progression.

overall_design: We performed MeRIP sequencing to identify genes related to cell growth and chromosome segregation whose m6A modifications are regulated by WTAP knockdown in comparison to the control group


title: Aging promotes a RAGE-dependent increase in breast cancer metastasis

city: Washington

first: Jiaxiang

last: Tao

state: DC

address: 3970 Reservoir Road NW

department: Oncology

institute: Georgetown University

summary: Breast cancer incidence and mortality increase with age, but the mechanisms linking aging to metastasis remain unclear. Most preclinical studies use young animal models, limiting insight into how the aged microenvironment influences cancer. Here, we show that aging markedly increases breast cancer metastasis in multiple mouse models, and this effect is dependent on host expression of the Receptor for Advanced Glycation End-products (RAGE). Aging increased tumor RAGE ligand levels, including S100A8/9 and AGEs, and induced RAGE-dependent changes in inflammatory, EMT, angiogenic, and extracellular matrix gene programs in tumors. Circulating cytokines and S100A8/9 from aged hosts promoted tumor cell invasion, which was suppressed by RAGE or S100A8/9 inhibition. In human breast cancers, elevated AGER expression and enrichment of aging- and RAGE-associated transcriptional signatures correlated with poorer survival, especially in older patients. These findings identify RAGE as a mechanistic link between aging and metastasis and a potential therapeutic target in older patients.

overall_design: RNA-seq profiling of primary mouse breast tumors from wild-type and RAGE knockout young (3 months old) and aged (21 months old) mice.

first: P.

last: Miller

first: J.


title: Metabolite-induced DNA damage drives stochastic stem cell loss and clonal hematopoiesis

city: Cambridge

first: Bertie

last: Gottgens

email: bg200@cam.ac.uk, nkw22@cam.ac.uk

address: Jeffrey Cheah Biomedical Centre

country: United Kingdom

institute: University of Cambridge

summary: DNA damage and mutations in hematopoietic stem cells (HSC) enable clonal hematopoiesis (CH). Such damage occurs throughout life, but its origins remain unknown. Here, we demonstrate that endogenous formaldehyde causes HSC attrition and subsequently CH. We generated conditional mouse models lacking formaldehyde detoxification and Fanconi anemia (FA) DNA repair in blood. Formaldehyde protection was crucial from embryonic HSC emergence and throughout life. Despite a severe deficiency in HSCs, these mice produce blood for many months. To determine what enables this, we employed a new unbiased method for detecting clones which exploits somatic variant data. This revealed initial polyclonal hematopoiesis which diminishes to monoclonal CH, devoid of known genetic selection. Furthermore, in FA children, we find the same transition to monoclonal hematopoiesis. Therefore, DNA damage-induced attrition down to a last functional cell can be a driving force for CH, representing an alternative route to CH other than purely by fitness-enhancing selection.

overall_design: scRNA-seq was performed on Lin− cKit+ hematopoietic progenitor populations from spleen and bone marrow of conditional Adh5 and/or Fancd2 knockout mice and controls, using 10x Genomics 3’ v3 chemistry, to compare transcriptional states across genotypes.

first: Ashley

middle: N

last: Kamimae-Lanning

first: Jill

last: Brown

first: Matthias

last: Günther

first: Franziska

last: Hörsch

first: Holly

last: Russell

first: Lise

last: Larcher

first: Frédéric

last: Langevin

first: Tomoya

last: Isobe

first: Nicola

middle: K

last: Wilson

first: Felix

last: Dingler

first: Rebecca

last: Cordell

first: Meng

last: Wang

first: Christopher

last: Millington

first: Nina

last: Claudino

first: Ewa

last: Gogola

first: Matthew

last: Nicholls

first: Verena

last: Körber

first: Berthold

last: Göttgens

first: Marella

last: de Bruijn

first: Juan

middle: I

last: Garaycoechea

first: Jean

last: Soulier

first: Thomas

last: Höfer

first: Ketan

last: Patel


title: Periodontitis induces skeletal muscle atrophy by increasing circulating levels of activin A

city: Seoul

first: Yun-Sil

last: Lee

address: 1 Gwanak-ro, Gwanak-gu, Bldg 86/Rm 405

department: Department of Molecular Genetics

institute: Seoul National University

summary: Periodontitis, a chronic inflammatory disease, has been linked to various systemic conditions, including cardiovascular disease, type 2 diabetes, and premature birth. However, its impact on skeletal muscle remains unclear. Here, we utilize a ligature-induced periodontitis (LIP) mouse model and show that periodontitis significantly reduces muscle and bone mass without affecting fat mass or food intake. Interestingly, activin A, a well-documented inducer of muscle atrophy, was highly expressed in periodontitis-affected gingiva, surpassing its expression in the liver, a primary activin A-expressing organ. The activin A gene (Inhba) was highly expressed, particularly in gingival fibroblasts and epithelial cells, which undergo significant proliferation as periodontitis progresses, as well as in myeloid cells infiltrating inflamed periodontal tissues and in myeloid cell-derived osteoclasts. A similar upregulation pattern of INHBA was also confirmed in periodontitis-affected human tissues by scRNA-seq analysis. Furthermore, we demonstrate that serum activin A levels significantly increased in periodontitis-affected mice, while the intra-gingival injection of siInhba significantly reduced activin A levels and restored muscle mass and myofiber size compared to the siCtrl injection. Our findings indicate that activin A is a key mediator of muscle atrophy in periodontitis and that local injection of siInhba can prevent periodontitis-induced muscle atrophy without causing systemic adverse effects.

overall_design: Gingival tissues from healthy control mice and from mice 3 days after ligature-induced periodontitis (LIP) induction were analyzed. Each condition included three independent biological replicates. Single-cell RNA sequencing was performed using the 10x Genomics platform to characterize cell type-specific transcriptional responses to periodontitis. Beyond inducing local inflammation, periodontitis alters the expression of genes encoding secreted factors with potential systemic effects. This dataset identifies the cell populations that exhibit these transcriptional changes and provides their disease-associated gene expression profiles.

first: Wonn

last: Shim


title: Physiological perfusion of human vasculature reveals a YAP/TAZ-Apelin switch linking intraluminal flow to endothelial state transitions and vessel remodeling [Bulk RNA-seq]

first: Jeff

last: Wrana

overall_design: Bulk RNA sequencing of vascular beds extracted from the VIVOS platform after 1, 2, 4 or 8 days, using low flow (300 RPM impeller speed) or high flow (900 RPM impeller speed).

first: Tiger

last: Jian

first: Adam

last: Sivitilli

first: Yaxin

last: Guo

first: Callum

last: Stirton

first: Jessica

last: Gosio

first: Yuko

last: Tsukahara

first: Johnny

last: Tkach

first: Suying

last: Lu

first: Amin

last: Yarmand

first: Maria

last: Mangos

first: Rod

last: Bremner

first: Jeffrey

first: Liliana

last: Attisano

first: Laurence

last: Pelletier


title: Effect of palmitate treatment on transcriptome in Pompe disease patient fibroblasts

city: Paris

first: Ganna

last: Panasyuk

address: 156-160 Rue Vaugirard, Faculté de Médecine Paris Descartes,, 4th Floor - Lab-408/Office-404,, 4th Floor - Lab-408/Office-404,

country: France

institute: Inserm U1151/CNRS UMR 8253, Necker Enfants Malades Institute (INEM)

summary: Lysosomal storage disorders (LSDs) are rare inherited diseases caused by mutations in lysosomal proteins, leading to substrate accumulation and lysosomal dysfunction. Whether this build-up compromises lysosomal membrane integrity remains an open question. In this study, we aimed to investigate the presence of lysosomal membrane damage in LSD cells and to identify mechanisms that could reveal potential therapeutic strategies for amelioration of cellular physiology. Methods: Primary skin fibroblasts from Pompe disease patients were used to evaluate lysosomal integrity and function. Pharmacologic and metabolite treatments were applied in loss-of-function and rescue analyses, and transcriptomics analysis was done under these conditions. Results: In Pompe disease, caused by mutations in the acid alpha-glucosidase gene, glycogen accumulation, palmitate treatment improved lysosomal function in fibroblasts from patients, with no significant effect at transcriptional level. Conclusions: These findings open to novel therapeutic opportunities for improvement of lysosomal function through development of treatments that target fatty acid metabolism.

overall_design: Skin fibroblasts of a Pompe disease patient were treated for 24 hours with BSA-palmitate (200 µM) compared to treatment by fatty acid-free BSA (BSA), followed by PE-100 Poly-A enriched RNA-seq  (n=3 replicates).

first: Edouard

last: Le Guillou

first: Arianna

last: Segaloni

first: Alexis

last: Gadault

first: Nathaniel

middle: F

last: Henneman

first: Min

last: Su

first: Ivan

last: Nemazanyy

first: Catia

last: Oliveira Dias

first: Nesrine

last: Hifdi

first: Valérie

last: Nivet-Antoine

first: Michael

last: Laemmerhofer

first: Karim

last: Hnia

first: Catherine

last: Caillaud


title: BCOR mutations deregulate cell cycle and hypoxic adaptation pathways in retinoblastoma

city: Miami

first: Jeffim

last: Kuznetsoff

state: FL

address: 1501 NW 10th Avenue

department: Ophthalmology

institute: University of Miami

summary: Retinoblastoma (RB) is the most common pediatric eye cancer. Most cases of RB are initiated by bi-allelic mutational inactivation of the RB1 gene. After RB1, the gene that is most commonly mutated gene in RB is BCOR, which is mutated in approximately 20% of RB tumors and is associated with a more aggressive tumor phenotype and worse patient outcomes. Here, we interrogated BCOR in low passage RB cell lines using RNA sequencing. We show that loss of BCOR downregulates the expression of genes associated with cell cycle regulation and upregulates genes associated with hypoxic adaptation.

overall_design: RNAseq profiling of low passage RB cell lines and their BCOR knockdown derrivates  14 days after stable integration of lentiviral particles expressing shRNA against BCOR.

first: Michelle

last: Zhang


title: RNF25 confers tolerance to azacytidine-induced mRNA damage by curbing activation of the integrated stress response [Ribo-seq]

city: Munich

first: Julian

last: Stingele

address: Butenandtstraße 1

institute: LMU Munich

summary: Excessive RNA damage activates cellular stress responses, triggering cell death. However, pathways that negatively regulate RNA damage responses are largely uncharacterized. Using genetic screens, we here find that the ubiquitin ligase RNF25 provides tolerance to RNA damage caused by the nucleoside analogue azacytidine, a chemotherapeutic agent used to treat acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS). Mechanistically, azacytidine is incorporated into mRNA, where it causes lesions that stall elongating ribosomes , leading to cytotoxic activation of the GCN2-dependent integrated stress response (ISR). RNF25 prevents ISR hyperactivation by ubiquitylation of ribosomal protein eS31, suppresses cell death upon azacytidine tretament. Our study reveals an mRNA damage tolerance mechanism that determines cellular survival in response to azacytidine, highlighting RNA damage-induced stress response as a potentially critical component of chemosensitivity in AML and MDS.

overall_design: Ribo-Seq with HAP1 WT cells pre-treated with 1 µM GCN2i for 1 h, followed by 2 h treatment with 20 µM aza-C and GCN2i and 2 h recovery with GCN2i.

first: Carla

middle: M

last: Engel

last: Bagaric

first: Jonathan

last: Bohlen


title: RNF25 confers tolerance to azacytidine-induced mRNA damage by curbing activation of the integrated stress response [RNA-seq]

overall_design: RNA-Seq with HAP1 AAVS1, RNF25 KO, GCN2 KO, RNF25 GCN2 DKO, ZNF598 KO and eS31 K113R cells treated or not with azacytidine or halofuginone.

first: Shubo

last: Zhao

first: Julia

last: Philippou-Massier

first: Alexander

last: Graf

first: Stefan

last: Krebs


title: Transcriptomic analysis of fetal sheep liver across gestation (Gestational days 100, 124, and 144)

city: Sendai

first: Hideyuki

last: Ikeda

state: Miyagi

address: 1-1 Seiryo-machi

department: Pediatrics

institute: Tohoku university hospital

summary: The fetal liver plays a central role in metabolic and immune adaptation during development. We performed bulk RNA sequencing of ovine fetal liver at gestational days 100, 124, and 144 to characterize transcriptional changes associated with hepatic maturation.

overall_design: Fetal sheep liver samples were collected at three gestational stages (Gestatinal days 100, 124, 144; n=4, 5, and 6, respectively). Bulk RNA sequencing was performed to assess transcriptomic changes across developmental stages.


title: RNF25 confers tolerance to azacytidine-induced mRNA damage by curbing activation of the integrated stress response [TTchem-seq]

overall_design: TT-chem Seq with HAP1 cells treated or not for 1h or 5h with 1uM RNAPI inhibitor  (BMH-21), 100uM RNAPII inhibitor (DRB) or 20uM RNAPIII inhibitor (ML-60218).

first: Diana

last: van den Heuvel

first: Martijn

last: Luijsterburg

first: Marlis

last: Fischaleck


title: Bilayer Bio-instructive Conduits Drive Neuropathic Pain Relief via Multi-level Molecular Reprogramming

city: Chengdu

first: Guihua

last: Wei

address: No.111, North 1st Section, 2nd Ring Rd

institute: Southwest Jiaotong University

summary: Peripheral nerve injury (PNI) frequently progresses into chronic neuropathic pain (NP) when the early-stage regenerative microenvironment fails to stabilize, subsequently triggering peripheral and central sensitization. In this study, an autonomous, bio-instructive bilayer nerve guidance conduit (NGC) is engineered, integrating a piezoelectric PLLA inner layer (output 1151.35 mV) with a ropivacaine (RVC)-loaded PCL outer layer (83.63% release over 14 days). This dual-functional platform aims to achieve synchronized structural restoration and long-term analgesia. In vitro, the piezo-induced surface potentials triggers Ca2+ mobilization and activates the NGF, GDNF Mmp-9, Jun, Olig1, and Shh genes, promoting Schwann cells (SCs) proliferation, migration, and phenotypic reprogramming, which effectively blocked the peripheral sensitization. In vivo, using a rat chronic constriction injury (CCI) model, PLLA-PCL-RVC@NGC significantly alleviates mechanical, thermal, and cold hypersensitivity while accelerating functional recovery (SFI), thereby preventing the central sensitization. RNA-seq and serum analysis reveal that the device modulates TNF-α/NF-κB, IFN-α/γ, and IL-6 cytokines. This was evidenced by the significant downregulation of IgG, TGF-β1, S100, NF200, MMP-9, and Fcgr1A genes, alongside enhanced regenerative markers. By synergizing autonomous autonomous piezo-potentials with the sustained release of RVC, this bio-instructive NGC effectively attenuates both peripheral and central sensitization, thereby averting the onset of NP.

overall_design: To decipher the in vivo molecular mechanisms by which the piezoelectric-ropivacaine nerve conduit alleviates neuropathic pain and promotes nerve repair, a comparative transcriptomic analysis was performed on sciatic nerve tissues. Samples were harvested from a rat model of sciatic nerve chronic constriction injury (CCI). The study compared the transcriptomic profiles of the injured nerves treated with the piezoelectric-RVC conduit against the injured, untreated control group. RNA sequencing was conducted on these tissue samples. Differential expression analysis, followed by functional enrichment analysis (such as GO and KEGG pathway analysis), was performed to identify key genes and pathways involved in pain modulation, Schwann cell-mediated repair, and inflammatory response altered by the conduit treatment.

first: Haoyan

last: Wang

first: Huiyuan

first: Zaiqi

last: Li

first: Mengqi

last: Huang

first: Yuee

last: Dai

first: Shuxin

last: Qu

first: Jialuoyang

last: Chen


title: A Light-Driven Bioactive Nerve Conduit for Trigeminal Neuralgia: Integrated Decompression and Photosynthetic Oxygenation Restores Mitochondrial Function

summary: Vascular compression and concomitant hypoxia exacerbate trigeminal neuralgia (TN), yet current therapies rarely target both pathologies. We developed a photosynthetic nerve guide conduit (SFM-Gel@ NGC) by embedding auto fluorescent microalgae in silk fibroin hydrogel, enabling simultaneous mechanical decompression and oxygen release. The construct exhibited suitable mechanical properties, tunable oxygen generation, and excellent biocompatibility. Under hypoxia, SFM-Gel promoted neuronal cell proliferation and function by reducing ROS and restoring mitochondrial activity, while downregulating HIF-1α and ATP/P2X3 pathways. In a rat TN model, auto fluorescent SFM-Gel@ NGC implantation alleviated mechanical allodynia, repaired nerve morphology, and suppressed BDNF/NGF and ATP/P2X3 inflammatory signaling. Transcriptomic analysis confirmed modulation of hypoxia/ROS/NF-κB pathways during immune/inflammatory responses to compression. This integrated decompression-oxygenation strategy offers a transformative therapy for TN.

overall_design: To elucidate the molecular mechanisms underlying the therapeutic effect of SFM-Gel @NGC-Light on trigeminal neuralgia, a comparative transcriptomic analysis was conducted. Total RNA was extracted from trigeminal ganglia of two experimental groups: the chronic constriction injury of the infraorbital nerve (CCI-ION) model group and the SFM-Gel @NGC-Light treatment group. RNA sequencing was performed on the Illumina NovaSeq 6000 platform (150-bp paired-end). Differential expression analysis identified genes significantly altered by the treatment, followed by functional enrichment analysis of Gene Ontology (GO) terms, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways, and hallmark gene sets. This design aims to define the transcriptomic reprogramming associated with pain alleviation and neural repair.

first: Qing

last: Ye

first: Jieling

first: Xiong

last: Xiong

first: Ludi

last: Zhang

first: Ling


title: Meiotic prophase I disruption as a strategy for non-hormonal male contraception using small-molecule inhibitor JQ1 [RNA-seq]

city: Ithaca

first: Paula

last: Cohen

address: 618 Tower Rd

institute: Cornell University

summary: The small-molecule bromodomain inhibitor JQ1 transiently suppresses spermatogenesis by targeting BRDT, a testis-specific transcriptional regulator required for meiotic and post-meiotic differentiation. To define the transcriptional and cellular consequences of JQ1 exposure and recovery, we performed single-cell RNA sequencing (scRNA-seq) of mouse testes collected from untreated controls, JQ1-treated males, and recovery cohorts following treatment withdrawal. This dataset includes 15 libraries representing all experimental groups and captures germ cell and somatic populations spanning spermatogonial, meiotic, and spermiogenic stages. The data provide a comprehensive transcriptional atlas of JQ1-induced meiotic disruption and subsequent restoration of spermatogenesis, supporting mechanistic and contraceptive studies of BRDT inhibition.

overall_design: Adult male DBA/2J mice received the bromodomain inhibitor JQ1 (50 mg/kg, intraperitoneal, once daily for 3 weeks) or vehicle control. Testes, liver, and kidney were collected to profile both immediate and post-withdrawal effects. Testis single-cell RNA-seq (scRNA-seq) was generated from five cohorts: (i) untreated controls (UC), (ii) vehicle-treated controls at the treatment endpoint (VC-T), (iii) JQ1-treated at the treatment endpoint (T), and recovery cohorts 6 weeks post-withdrawal—(iv) JQ1 recovery (R) and (v) vehicle-treated recovery (VC-R). For scRNA-seq, single-cell suspensions from individual testes were processed with the 10x Genomics Chromium 3′ v3.1 workflow and sequenced on an Illumina NovaSeq 6000; after Cell Ranger QC, 15 libraries (3 biological replicates per cohort) were retained and integrated in Seurat for downstream analyses of JQ1-induced transcriptional changes, germ-cell population dynamics, and recovery kinetics. In parallel, bulk RNA-seq was performed on liver and kidney (n = 10 samples per organ: 3 treatment, 3 recovery at 6 weeks post-withdrawal, and 4 controls comprising untreated and vehicle-treated samples) to assess systemic transcriptional responses and reversibility outside the reproductive tract.

first: Stephanie

last: Tanis


title: Meiotic prophase I disruption as a strategy for non-hormonal male contraception using small-molecule inhibitor JQ1

overall_design: Adult male DBA/2J mice were administered the bromodomain inhibitor JQ1 (50 mg/kg daily, 3 weeks, intraperitoneal) or vehicle control. Testes were collected from (i) untreated controls (UC), (ii) vehicle-treated controls (VC-T), (iii) JQ1-treated males at endpoint (T), and (iv) recovery cohorts (R, VC-R) 6 weeks post-withdrawal (R). Single-cell suspensions were prepared from individual testes, and libraries were generated using the 10x Genomics Chromium 3′ v3.1 platform. Sequencing was performed on an Illumina NovaSeq 6000. After Cell Ranger processing and quality control, 15 libraries (3 biological replicates per condition) were retained for downstream integration and analysis using Seurat. The dataset supports examination of JQ1-induced transcriptional changes, germ cell population dynamics, and recovery kinetics.


title: Gene expression profile of FFPE primary Her2-positive breast cancer samples from patient who were subjected to  neoadjuvant therapy

city: Sevilla

first: María

middle: Ángeles

last: Domínguez

state: Seleccione

address: Avenida Manuel Siurot s/n

institute: Instituto de Biomedicna de Sevilla

summary:
Pathological complete response (pCR) after neoadjuvant therapy is a robust surrogate marker for long-term outcomes in breast cancer. However, reliable biomarkers predicting pCR in HER2-positive breast cancer remain elusive
Transcriptomic profiling to identify candidate genes associated with pCR were performed in patients with HER2-positive, hormone receptor–negative breast cancer treated with neoadjuvant chemotherapy plus anti-HER2 agents

overall_design: Patients were retrospectively selected at Virgen del Rocío Hospital (Seville, Spain). The neoadjuvant treatment they received consisted of standard chemotherapy (anthracyclines and/or taxanes) combined with anti-HER2 agents alone (trastuzumab) or in combination (trastuzumab and pertuzumab). The patients were stratified according to their response to neoadjuvant treatment according to the residual cancer burden (RCB) classification. The responders were those who achieved a complete pathological response (RCB-0), whereas the nonresponders included patients with residual disease after treatment (RCB-I, II or III).  RNA extraction was performed from 8–10 10 µm sections of formalin-fixed paraffin-embedded (FFPE) samples obtained from diagnostic biopsies using a RecoverAll™ Total Nucleic Acid Isolation Kit (Thermo Fisher Scientific, Waltham, MA, USA) according to the manufacturer's recommendations with modifications in the protease digestion stage, where prolonged incubation at 50 °C for three hours was used to optimize the recovery of nucleic acids.  Gene expression analysis in Cohort 1 was carried out using a Clariom D microarray (Thermo Fisher Scientific, Waltham, MA, USA), which is based on Affymetrix microarray technology. Washing and scanning were performed using the Affymetrix GeneChip system, which includes a GeneChip 645 Hybridization Oven, a GeneChip 450 Fluid Station and a GeneChip 7G Scanner.  Gene expression data were normalized and analyzed using the Transcriptome Analysis Console (TAC) 4.0 software (Thermo Fisher Scientific). To identify differentially expressed genes between patients with and without CRp, the criterion of a change in expression greater than 1.5 or less than -1.5 in terms of fold change was applied, with a p value less than 0.05.

first: Ana

last: Gil-Torralvo

first: María A.

last: Domínguez-Cejudo

first: Sonia

last: Molina-Pinelo

first: Carmen

last: Garrigós

first: Marta

last: Benavent-Viñuelas

first: Alejandro

last: Falcón

first: Monica

last: Cejuela

first: Manuel

last: Ruiz-Borrego

first: Javier

last: Salvador-Bofill


title: Senescent Endothelial Cells in Cerebral Microcirculation Are Key Drivers of Age-Related Blood-Brain Barrier Disruption, Microvascular Rarefaction, and Neurovascular Coupling Impairment in Mice

city: Oklahoma City

first: Roland

last: Patai

state: Oklahoma

address: 975 NE 10th street

department: Department of Neurosurgery

institute: University of Oklahoma Health Campus

summary: With advancing age, neurovascular dysfunction manifests as impaired neurovascular coupling (NVC), microvascular rarefaction, and blood-brain barrier (BBB) disruption, contributing to vascular cognitive impairment (VCI). Our previous research established a causal link between vascular senescence induced cerebromicrovascular dysfunction and cognitive decline in accelerated aging models. The present study examines whether chronological aging promotes endothelial senescence, adversely affecting neurovascular health, and whether senolytic therapies can enhance neurovascular function and cognitive performance in aged mice. We used transgenic p16-3MR mice to identify and eliminate senescent cells and employed genetic (ganciclovir) and pharmacological (ABT263/Navitoclax) senolytic approaches. Evaluations included spatial memory performance, NVC responses, cortical microvascular density, BBB permeability, and detection of senescent endothelial cells via flow cytometry. Brain endothelial cells exhibited heightened sensitivity to aging-induced senescence, undergoing senescence at a greater rate and earlier than other brain cell types, particularly during middle age. This microvascular endothelial cell senescence was associated with NVC dysfunction, microvascular rarefaction, BBB disruption, and deteriorating cognitive performance. On the other hand, senolytic treatments in aged mice improved NVC responses, BBB integrity, microvascular density, and learning capabilities. Notably, these findings suggest that the most effective time window for senolytic treatment is in middle-aged mice, where early intervention could better prevent neurovascular dysfunction and mitigate age-related cognitive impairment.

overall_design: The authors used single-cell RNA sequencing to identify senescent brain microvascular endothelial cells across aging in p16-3MR mice. Brains were collected after PBS perfusion from young and aged mice, with n = 5 animals per group, dissociated into single-cell suspensions, cleared of debris, and enriched for viable cells by low-pressure FACS after SYTOX Green live/dead staining. The resulting cells were loaded onto the 10x Genomics Chromium Single Cell 3′ platform, libraries were prepared with the Single Cell 3′ v2 kit, and sequencing was performed on an Illumina NovaSeq 6000.

first: Anna

last: Csiszar

first: Zoltan

last: Ungvari

first: Tripti

last: Gautam

first: Tae-Gyu

last: Oh

first: Jenny

middle: R

last: Gipson

first: Makayla

last: Foster


title: Comprehensive analysis of non-tumor lung, liver, and kidney transcriptomes in metastatic osteosarcoma

city: Bethesda

first: Anjali

last: Garg

state: Maryland

address: Building 10, Room 1B53

department: Comparative Oncology Program,NCI

institute: National Institute of Health

summary: Landscape of the peritumoral TME of metastatic osteosarcoma and further underscore the translational relevance of the canine patient as a model of human disease.

overall_design: Our study identifies shared and tissue-specific changes in met-recipient non-tumor lung, liver, and kidney which overlaps with transcriptional alterations described in human cancers.

first: J

last: Beck

first: A

first: P

last: Choyke

first: C

last: Mazcko

last: LeBlanc


title: Accessible chromatin profile of early life and adult origin B cell populations

city: Atlanta

first: Chris

last: Scharer

state: GA

address: 1510 Clifton Rd, Suite 3086A

department: Microbiology and Immunology

institute: Emory University

summary: The adult B cell pool is a developmental mosaic comprising cells of early life (ELO) and adult origin.  To further understdand the differences between B cells of each origin we used a genetic time stamping approach to lable ELO B cells and FACS isolate from the spleen naive follicular and marginal zone B cells, B1 B cells from the peritoneal cavity, and memory B cells (MBC) from the peyer's patch.  The assay for transposase accessible chromatin sequencing (ATAC-seq) was performed on each population to identify epigenetic programming that corresponded to ELO versus adult derived B cells.

overall_design: ATAC-seq of early life derived and adult derived B cell populations from three organs.  Four replicates were analyzed for each sample group.

first: Christopher

middle: D

first: Joan

last: Yuan


title: Gene expression profile of NK cells sorted from the lymph node of tumor free C57BL/6J mice and tumor bearing lymph node in Diffuse large B cell lymphoma model of lymphatic or hematogenous.

city: Bellinzona

first: Santiago

last: Gonzalez

address: Via Francesco Chiesa 5

country: Switzerland

institute: Institute for Research in Biomedicine (IRB)

summary: The cellular components of the tumor microenvironment (TME) in non-Hodgkin B cell lymphoma demonstrate remarkable diversity. Recent evidence suggests that the spatial organization of malignant, immune and stromal cells within the TME is associated with clinical outcome and response to therapy. Yet, whether tumor cells distribution within the distinct nodal compartments, following lymphatic or hematogenous dissemination further influence the shaping of the TME and the antitumoral immune response remains unclear. We used Bulk RNA sequencing to analyze the diversity transcriptomic profiles of NK cells in 3 different conditions.

overall_design: We used RNA sequencing analyze the transcriptomic profiles of NK cells in 3 different conditions (Tumor free condition and tumor bearing mice with diffuse large B cell lymphoma disseminated either through the lymphatic system or blood vessels)

first: Kamil

last: Chahine

last: González


title: Gene expression profile of Eµ-myc lymphoma cells in cell culture and sorted from the LN of C57BL/6J mice following their dissemination through lymphatic or hematogenous routes.

summary: The cellular components of the tumor microenvironment (TME) in non-Hodgkin B cell lymphoma demonstrate remarkable diversity. Recent evidence suggests that the spatial organization of malignant, immune and stromal cells within the TME is associated with clinical outcome and response to therapy. Yet, whether tumor cells distribution within the distinct nodal compartments, following lymphatic or hematogenous dissemination further influence the shaping of the TME and the antitumoral immune response remains unclear. We used Bulk RNA sequencing to analyze the diversity transcriptomic profiles of Eµ-myc lymphoma in 3 different conditions.

overall_design: We performed bulk RNA sequencing on lymph node sorted lymphoma cells, disseminated either via lymphatic vessels or systematically through blood, collected respectively on day 11 and 18 post tumor injection, as well as on lymphoma cells taken directly from culture.


title: NAE1/UBA3-UBE2M are E1 and E2 Enzymes for the Urm1 Modification in Human Cells

city: Houston

first: Wenyue

last: Cao

state: TX

address: 7255 Helix Park Ave

institute: Texas A&M University

summary: Ubiquitin-related modifier 1 (Urm1) is an evolutionarily conserved ubiquitin-like protein. In eukaryotes, it serves dual roles as a sulfur donor for tRNA modification and a posttranslational protein modifier. Urm1 is proposed to be a primitive protein modifier and a potential precursor to the more complex ubiquitin system. However, no specific activating enzyme (E1), conjugating enzyme (E2), or ligase (E3) has been reported for the Urm1 modification cascade in human cells. In this study, we design an activity-based Urm1 probe to covalently capture cysteine enzymes functioning in the Urm1 signaling pathway. Through proteomic characterization and cell-based validation, we identify NAE1/UBA3 and UBE2M as E1 and E2 enzymes, respectively, for the urmylation pathway under both normal and oxidative stress conditions. Our results also indicate that DCN1 serves as an E3 ligase for the Urm1 modification in human cells. Bioinformatic analysis further reveals that genetic knockdown of NAE1, UBE2M, and Urm1 affects overlappingly genes associated with pathways controlling cellular response to stress conditions or with implications in liver diseases. Urm1 serves a protective role against oxidative stress. Pevonedistat, a potent NAE1 inhibitor that blocks protein urmylation in human cells, exhibits strong synergy with cisplatin, an agent known to induce oxidative stress, in killing liver cancer cells effectively.

overall_design: To understand gene expression patterns regulated by URM1 and its two controlling enzymes NAE1/UBA3 and UBE2M, transcriptomic profiling was performed on HEK293T cells treated with three siRNAs targeting NAE1, UBE2M, and URM1 genes.


title: True cyst formation in Tritrichomonas foetus: a survival and drug-resistance strategy redefining protozoan biology

city: Chascomús

first: Andrés

middle: Mariano

last: Alonso

state: Buenos Aires

address: Av. Intendente Marino Km 8.2

country: Argentina

institute: INTECH

summary: Tritrichomonas foetus, a protozoan parasite responsible for bovine and feline trichomonosis, has traditionally been considered to form only pseudocysts. Here, we reveal that T. foetus produces true cysts characterized by chitin like components-rich, fibrillar walls, cytoskeletal reorganization, and resistance to detergent treatment. Cystogenesis is induced by environmental stresses such as nutrient deprivation, alkaline pH mimicking the bovine preputial milieu, and exposure to metronidazole, a frontline antiparasitic drug. This encystation enhances parasite survival and suggests a novel drug-resistance mechanism. Transcriptomic profiling identifies key pathways involved in cyst wall biosynthesis and regulation, including Myb-like transcription factors and calcium/calmodulin dependent kinases. Encysted parasites also undergo DNA replication without cytokinesis, suggesting a strategy for rapid multiplication through multiple fission upon excystation. Our findings fundamentally reshape the understanding of T. foetus biology, highlight a critical stage in its transmission cycle, and have significant implications for therapeutic and diagnostic strategies in veterinary parasitology

overall_design: RNAseq profiling for T. foetus K strain incubated in standard culture media (untreated) and under nutrient restriction conditions for 48 hours (treated).

first: Lucrecia

middle: S

last: Iriarte

first: Andres

first: Cristian

last: Martinez

first: Maria

last: Prandi

first: Luiz

last: Barros

first: Marcos

last: Ferrante

first: Natalia

last: de Miguel

first: Veronica

last: Coceres


title: Transcriptomic profiling of chlorogenic acid and taurine treatment in human skin cells provides insights into cellular senescence mechanisms

city: Gangnam-gu

first: Hong-Hee

last: Won

address: 81, Irwon-ro

institute: SungKyunKwan University

summary: Chlorogenic acid (CGA) and taurine are well-known antioxidant compounds that have been demonstrated to reduce cellular senescence in the skin. Given their potential synergistic effects, co-treatment with CGA and taurine may enhance their individual efficacy. However, the biological mechanisms underlying their skin-protective effects remain underexplored. This study aimed to identify genes responsive to CGA and taurine and elucidate their anti-senescence-associated pathways. To this end, we conducted transcriptome-wide RNA sequencing to profile gene expression changes of human epidermal keratinocytes, melanocytes, and fibroblasts by treatment of CGA, taurine, and their combination. The differential expression analysis identified 197 differentially expressed genes (DEGs) in response to the compounds, of which 62 were prioritized as aging-related DEGs based on their involvement in skin aging pathways from functional enrichment analysis and supporting evidence from public databases and prior studies. By identifying key genes and pathways that might contribute to the cellular longevity in human skin, this study provides molecular insights for developing anti-aging strategies with potential applications in dermatology.

overall_design: RNA-seq profiling of skin keratinocytes, melanocytes, and fibroblasts treated with chlorogenic acid and taurine, chlorogenic acid alone, taurine alone, or left untreated.

first: Beomsu

last: Kim

first: Joong-Gon

last: Shin

first: In-Shik

last: Hong

first: Yeeun

last: Ahn

first: Jung Yeon

last: Seo

first: Jae Young

first: Sooyeon

last: Lee

first: Seung-Hyun

last: Jun

first: Eui Taek

last: Jeong

first: Hyunbin

last: Cho

first: Miso

last: Park

first: Dansay

first: Nae Gyu

last: Kang

first: Yunkwan