title: Deep learning identifies Pbx1 as a network hub of hematopoietic stem cell aging [Pbx1 RNA-seq]

city: Sendai

first: Keiyo

last: Takubo

address: 2-1 Seiryo-machi Aoba-ku

department: Graduate School of Medicine

institute: Tohoku University

summary: Hematopoietic stem cells (HSCs) constitute a well-structured hematopoietic system that undergoes an age-related bias toward myeloid/platelet differentiation. The mechanism by which this aging hallmark is deeply embedded in intrinsic HSC programs is unknown. Using single-cell RNA-seq data, old HSCs harbor two distinct transcriptional programs: one shared with megakaryocytes and the other associated with the most primitive HSCs. By employing a transformer-based model that captures higher-order differences between young and aging HSCs and integrating time-series transcriptomic analyses, epigenetic studies, and comprehensive transcription factor screens, we identified Pbx1 as a central gene controlling both age-related transcriptional programs and differentiation defects in old HSCs. Pbx1 suppresses erythroid differentiation by repressing Gata1 expression. In addition, we found that the histone methyltransferase G9a/GLP acts as an epigenetic regulator that specifically inhibits Gata1 expression and erythroid differentiation. These findings provide insight into the differentiation defects associated with stem cell aging and potential strategies for rejuvenation.

overall_design: Either CD150+CD48-CD41-CD34- LSK cells from 4 young (2.5mo) mice per sample, or CD150+CD48- CD34- LSK cells from 1 old (18mo) mouse per sample was isolated. Each experimental sample comprised cells from four young mice or one old mouse per sample. All isolated cells underwent retroviral transduction with mock or Pbx1-expressing vectors, after which 5,000 GFP+ cells for RNA-seq and 50,000 GFP+ cells for ATAC-seq were selected. These were then subjected to RNA-seq and ATAC-seq (n = 3 biological replicates).

first: Hiroshi

last: Kobayashi

first: Miho

last: Haraguchi

first: Shinpei

last: Tamaki


title: Hyodeoxycholic Acid Suppresses Hepatosteatosis via GLP-1/iNKT Cell Crosstalk and PPARα Activation (scRNAseq_CD4+ lymphocytes)

status: Public on Jul 13 2026

city: Chiba

first: Eunyoung

last: Lee

address: 1-8-1 Inohana, Chuo-ku

department: Department of Medical Physiology

country: Japan

institute: Chiba University, Graduate School of Medicine

type: Expression profiling by high throughput sequencing

summary: Hepatosteatosis, a common liver condition, involves excessive lipid accumulation and can lead to severe complications. Its molecular mechanisms are poorly understood, highlighting the need for therapies.  The molecular mechanisms are poorly understood, emphasizing the need for effective therapies.  In this study, we identified hyodeoxycholic acid (HDCA) as a potent anti-steatotic agent capable of preventing diet-induced fatty liver.  Mechanistically, HDCA treatment enhanced the hepatic expression of numerous PPARα target genes while also promoting the secretion of the gut hormone GLP-1.  The significance of PPARα signalling was emphasised by the fact that the anti-steatotic effects of HDCA were completely abolished in PPARα-knockout mice.  Our findings further reveal a novel mechanism involving invariant natural killer T (iNKT) cells.  HDCA treatment increased both the number and proliferation of iNKT cells in vivo, a phenomenon recapitulated in vitro using a GLP-1 agonist.  This indicates that the anti-steatotic action of HDCA requires the coordinated activity of PPARα signalling and iNKT cells.  These insights offer a promising avenue for developing targeted therapies for MASLD.

overall_design: Mice were treated with different diets, normal diet (ND), 60% high fat diet (HFD), or 60% HFD plus 0.25% hyodeoxycholic acid (HDCA), respectiviely. After 12 weeks feeding, CD45+ cells in iver-resident mononuclear cells (MNCs) were isolated from WT and  Ja18-/- (iNKT KO) mice and were sorted using BD FACS Aria III (10,000 cells each).  Gene expression was evaluted using single cell RNA-seq and single cell T cell receptor (TCR)-seq in CD45+ lymphocytes.

first: Ryo

last: Hatano

first: Hayato

last: Yoshikawa

first: Yukihiro

last: Endo

last: Koyama-Nasu

first: Atsushi

last: Onodera

first: Motoko

last: Y. Kimura

first: Takashi

last: Miki


title: Deep learning identifies Pbx1 as a network hub of hematopoietic stem cell aging [Pbx1 Cut&Tag]

type: Genome binding/occupancy profiling by high throughput sequencing

overall_design: Either CD150+CD48-CD41-CD34- LSK cells from 4 young (2.5mo) mice per sample, or CD150+CD48- CD34- LSK cells from 1 old (18mo) mouse per sample was isolated. Each experimental sample comprised cells from four young mice or one old mouse per sample. All isolated cells underwent retroviral transduction with mock or Pbx1-expressing vectors, after which 50,000 GFP+ cells for Cut&Tag were selected (n = 3 biological replicates). Anti-H3K9me2 antibody was used to target chromatin regions bound by di-methyl histone H3.


title: Deep learning identifies Pbx1 as a network hub of hematopoietic stem cell aging [Pbx1 ATAC-seq]


title: Deep learning identifies Pbx1 as a network hub of hematopoietic stem cell aging [26hr RNA-seq]

overall_design: Each replicate (n = 2 biological replicates per group) consisted of a pool of 12 young mice (14 weeks old) and 2 old mice (25 and 28 months old). In each group, 3,000 CD150+CD48-LSK cells were sorted and either immediately subjected to RNA-seq for the fresh group or cultured for 26 hours under SF-O3 conditions supplemented with 4% BSA, 1 ng/mL SCF, 100 ng/mL TPO, and 1% O₂, followed by RNA-seq for the culture group.

first: Shintaro

last: Watanuki

first: Motohiko

last: Oshima

last: Iwama


title: R-loop maintains the deposition of H3K36me3 to prevent invasion of H3K4me3 during SN-oocyte development [3]

city: Guangzhou

first: Ying

middle: liang

last: Sheng

state: Guangdong

address: No. 9 XingDaoHuanBei Road, Guangzhou International Bio Island

country: China

institute: Guangzhou National Laboratory

summary: Establishment of epigenetic modifications in an orderly manner is crucial for oocyte maturation and embryonic development. R-loop (DNA/RNA hybrids) plays an important role in regulating genome stability, epigenetic modifications and gene expression. However, the specific functions and regulatory mechanisms of R-loop on the crosstalk between histone modifications during oocyte development remain unclear. Here, we find that loss of R-loop by overexpressing Rnaseh1 significantly slow down oocyte development. R-loop loss in germinal vesicle (GV) oocyte leads to downregulation of H3K36me3 at key oocyte developmental gene bodies, aberrant invasion of H3K4me3 into H3K36me3-marked regions, resulting in dysregulated gene expression and ultimately hindering oocyte development. Importantly, this dysregulated gene expression can be rescued by histone H3K36me3 methyltransferase SETD2 targeting on specific R-loop-dependent H3K36me3-marked regions. Together, this finding reveals that R-loop acts as a crucial regulator in controlling epigenetic crosstalk of H3K36me3 and H3K4me3 in maternal genome, ensuring normal oocyte development.

overall_design: ChIP-seq after overexpression of Rnaseh1 and mCherry in SN oocytes.

first: Yingliang

first: Tianyan

last: Guo

first: Hongjie

last: Yao


title: R-loop maintains the deposition of H3K36me3 to prevent invasion of H3K4me3 during SN-oocyte development [RNA-Seq]

overall_design: RNA-seq after overexpression of Rnaseh1 and mCherry in NSN and SN oocytes.


title: R-loop maintains the deposition of H3K36me3 to prevent invasion of H3K4me3 during SN-oocyte development [EM-Seq]

overall_design: EM-seq after overexpression of Rnaseh1 and mCherry in SN oocytes.


title: Single-cell mapping of chromosome breaks identifies multiple fragile site classes with distinct DNA replication timing landscapes [scRepli-seq]

city: Kobe

first: Jothivanan

last: Elumalai

state: Hyogo

address: 2-2-3, Minatojima Minamimachi, Chuo-ku

department: Biosystems Dynamics Research (BDR)

institute: RIKEN

summary: Common fragile sites (CFSs) are genomic regions susceptible to chromosome breaks. However, because they were identified using cell populations, low-frequency fragile sites (non-CFSs) could have been overlooked. Here we perform single-cell genome-wide mapping and classification of aphidicolin-induced chromosome breaks. In human osteosarcoma cells, 42% of breaks exhibit features of CFSs. The remaining 58% are non-CFSs that are ‘rare’ and replicate throughout the S-phase. Among non-CFSs, we identify early-S replicating breaks associated with transcription-replication conflicts, as well as two additional break classes. One is dependent on transcription and coincides with early-to-late-S replication timing (RT) transition regions, while another class exhibits late-S RT with its frequency increasing upon transcription inhibition. Intriguingly, we find that distinct RT landscapes are associated with aphidicolin-induced RT behavior and break classes. Our data reveal the frequencies, RT landscapes, and mechanistic differences among distinct break classes, providing a comprehensive view of genomic regions prone to breakage under replication stress.

sample_organism:
Homo sapiens
Mus musculus

platform_organism:
Homo sapiens
Mus musculus

overall_design: scRepli-seq experiment was performed in human osteosarcoma (U2OS) and CBMS1 mouse embryonic stem cells (mESCs), treated with or without low-dose aphidicolin for 24 hours. We only deposited single-cell data sets which passed our filtering steps.

first: Ichiro

last: Hiratani


title: Single-cell mapping of chromosome breaks identifies multiple fragile site classes with distinct DNA replication timing landscapes [BrdU-IP Repli-seq]

overall_design: BrdU-IP Repli-seq experiment was performed in human osteosarcoma (U2OS) and CBMS1 mouse embryonic stem cells (mESCs), treated with or without low-dose aphidicolin for 24 hours.


title: The effect of Glud1 inhibition of HSCs durgin ev vivo culture

city: Kumamoto

first: Terumasa

last: Umemoto

address: 2-2-1, Honjo, Chuo-ku

institute: Kumamoto University

summary: Self-renewing hematopoietic stem cells (HSCs) during hematopoietic regeneration showed lower intracellular glutamate (Glu) levels compared with dividing progenitor cells in the steady state and HSCs that attenuate stem cell features during ex vivo culture. Moreover, R162, an inhibitor of glutamine dehydrogenase (Glud1) that catabolize Glu into α-ketoglutarate, contributed to stem cell maintenance during HSC divisions. These data suggest that lower intracellular Glu levels during HSC division contributed to self-renewing divisions by suppressing Glud1-mediated reactions.

overall_design: After EPCRHigh HSCs were cultured for 5 days in the absence or presence of R162, whole obtained cells were subjected to scMultiome analysis.

first: Ayako

last: Nauamura-Ishizu

first: Ayano

last: Yahagi


title: mRNA profiles of activated hematopoietic stem cells under several conditions [RNA-Seq]

overall_design: After EPCRHigh or EPCRLow cells within the HSC fraction (CD150+ CD48- EPCR+ Lineage-) were cultured for 1 days under the conventional conditions, they were subjected to RNA-seq. In addition, after EPCRHigh cells within the HSC fraction (CD150+ CD48- EPCR+ Lineage-) were cultured for 4 days in the absence or presence of R162, a Glud1 inhibitor, newly generated EPCRHigh or EPCRLow HSCs were subjected to RNA-seq.


title: Chromatin accessibility profiles of activated hematopoietic stem cells under several conditions [ATAC-Seq]

overall_design: After EPCRHigh or EPCRLow cells within the HSC fraction (CD150+ CD48- EPCR+ Lineage-) were cultured for 1 days under the conventional conditions, they were subjected to ATAC-seq. In addition, after EPCRHigh cells within the HSC fraction (CD150+ CD48- EPCR+ Lineage-) were cultured for 4 days in the absence or presence of R162, a Glud1 inhibitor, newly generated EPCRHigh or EPCRLow HSCs were subjected to ATAC-seq.


title: The lineage master transcription factor, p63 recruits a cancer-specific cofactor, FOXK1 to mediate oncogenic 3D chromatin dynamics in squamous cell carcinoma [RNA-seq]

city: Stanford

first: Namyoung

last: Jung

state: CA

address: 269 Campus Dr. CCSR Room 2150

department: Medicine

country: USA

institute: Stanford University

summary: Transcriptional dysregulation by a lineage master transcription factor (TF) is a critical mechanism in cancer, involving alteration of three-dimensional (3D) chromatin architecture. However, the underlying mechanisms of altered master TF-dependent chromatin interactions in cancer cells remain unclear. Here, we employ multi-omic approaches to examine chromatin interactions dependent on p63, a master TF in epidermis, in squamous cell carcinomas (SCCs) compared to normal keratinocytes (KCs), integrating chromatin looping and accessibility, transcriptome, p63 binding and proteomics. p63 facilitates higher connectivity between the promoters of prognostic genes in SCCs, and distal enhancers.  Many SCC-specific p63-dependent genes are connected to SCC-specific p63-dependent epigenetic signature via a cis-regulatory element (CRE) without the signature, referred to as ‘Secondary’ regulation mode. Notably, we identify FOXK1 as a cancer-specific cofactor, cooperating with p63 to shape the oncogenic chromatin landscape, inhibiting cell proliferation. Our findings suggest the p63-FOXK1 axis as a potential target for cancer therapy in SCCs.

overall_design: 3' RNA-seq data of CAL27, SCC13  and undiffernetiated and differentiated keratinocytes from human subjects treated with control siRNA and siRNA targeting p63 with 2 biological replicates each. Note: For the keratinocyte raw data, these are primary human samples, so we CANNOT release, but we release processed data.


title: The lineage master transcription factor, p63 recruits a cancer-specific cofactor, FOXK1 to mediate oncogenic 3D chromatin dynamics in squamous cell carcinoma [ChIP-seq]

summary: Transcriptional dysregulation by a lineage master transcription factor (TF) is a critical mechanism in cancer, involving alteration of three-dimensional (3D) chromatin architecture. However, the underlying mechanisms of altered master TF-dependent chromatin interactions in cancer cells remain unclear. Here, we employ multi-omic approaches to examine chromatin interactions dependent on p63, a master TF in epidermis, in squamous cell carcinomas (SCCs) compared to normal keratinocytes (KCs), integrating chromatin looping and accessibility, transcriptome, p63 binding and proteomics. p63 facilitates higher connectivity between the promoters of prognostic genes in SCCs, and distal enhancers. Many SCC-specific p63-dependent genes are connected to SCC-specific p63-dependent epigenetic signature via a cis-regulatory element (CRE) without the signature, referred to as ‘Secondary’ regulation mode. Notably, we identify FOXK1 as a cancer-specific cofactor, cooperating with p63 to shape the oncogenic chromatin landscape, inhibiting cell proliferation. Our findings suggest the p63-FOXK1 axis as a potential target for cancer therapy in SCCs.

overall_design: ChIP-seq data of p63 in CAL27, SCC13 with 2 biological replicates each.


title: The lineage master transcription factor, p63 recruits a cancer-specific cofactor, FOXK1 to mediate oncogenic 3D chromatin dynamics in squamous cell carcinoma[HiChIP]

overall_design:
H3K27ac HiChIP data of CAL27, SCC13  and undiffernetiated and differentiated keratinocytes from human subjects treated with control siRNA and siRNA targeting p63 with 2 biological replicates each. Note: For the keratinocyte raw data, these are primary human samples, so we CANNOT release, but we release processed data.
>> Submitter states that raw data are not available for primary keratinocyte samples due to patient privacy concerns.<<<


title: The lineage master transcription factor, p63 recruits a cancer-specific cofactor, FOXK1 to mediate oncogenic 3D chromatin dynamics in squamous cell carcinoma [CUT&RUN]

overall_design: CUT&RUN data of FOXK1 in CAL27 with 2 biological replicates


title: Effect of knockdown PAK5 on gene expression of MB231 cells

city: Weifang

first: Zhenhai

last: Yu

address: No.288 Shengli East Street

institute: Weifang Medical University

summary: To investigate PAK5 in tumorigenesis, we established cell lines in which target gene has been knocked down by shRNA.

overall_design: Comparative gene expression profiling analysis of RNA-seq data for  cells and its KD derivatives (shPAK5).


title: The lineage master transcription factor, p63 recruits a cancer-specific cofactor, FOXK1 to mediate oncogenic 3D chromatin dynamics in squamous cell carcinoma[ATAC-seq]

overall_design:
ATAC-seq data of CAL27, SCC13  and undiffernetiated and differentiated keratinocytes from human subjects treated with control siRNA and siRNA targeting p63 with 2 biological replicates each. Note: For the keratinocyte raw data, these are primary human samples, so we CANNOT release, but we release processed data.

>> Submitter states that raw data are not available for primary keratinocyte samples due to patient privacy concerns.<<<


title: The Heme-regulated transcriptional repressor, BACH1 safeguards macrophage enhancer selection, activation andtissue adaptation [Capture Hi-C]

city: Debrecen

first: Laszlo

last: Nagy

address: Egyetem ter 1.

country: Hungary

institute: University of Debrecen

summary: Transcriptional master regulators of the myeloid lineage (like PU.1, Cebpa/b, etc.) are believed to be the main drivers of chromatin reprogramming during differentiation and polarization. Such developmental transcription factors act via their pioneer ability to open chromatin de novo and bookmark genomic regulatory sites (enhancers and promoters) to later recruit signal-dependent TFs, co-factors, and the basal transcriptional machinery. However, recent studies by us and others challenged this “developmental TF-centric” mode as they suggested that signal-dependent TFs, particularly repressors, can also have a pioneer and thus safeguarding role in the MF epigenome at baseline and during acute inflammation. Such an expanded model predicts that active transcriptional repression and chromatin bookmarking by signal-dependent master regulators are key mechanisms for safeguarding the enhancer repertoire and proper priming, deployment, and resolution of an inflammatory response. Here, we show that BACH1, a heme-sensitive transcriptional repressor, acts as such a pervasive epigenomic safeguard to regulate tissue macrophage identity. We show that BACH1 is part of the core hardwired transcriptional program of ground-state macrophages shaping the chromatin accessibility of thousands of distal regulatory elements. Furthermore, BACH1 cistrome is extensive, not static but dynamic, and expanding upon different inflammatory stimuli and correlates with pre-formed and de novo formed enhancer-promoter networks. We further show that myeloid BACH1 is indispensable in vivo for tissue regeneration upon injury as it regulates the kinetics of Ly6C+ to Ly6C- transition of inflammatory macrophages and regulates the onset, the kinetics and magnitude of expression of critical inflammatory and repair-related genes. Finally, BACH1 was found to be required in vivo for competitive fitness and tissue adaptation of several tissue-resident macrophage populations (eg. lung, peritoneal macrophages), further supporting its pervasive role in acquiring and maintaining the functional specificity and diversity of tissue macrophages. Taken together, our data suggest that BACH1 acts as a signal-dependent master regulator that directly controls key transcriptional circuits during tissue macrophage subtype function, specification and inflammatory responses in vivo.

overall_design: Transcriptomic and epigenetic profiling of WT and Bach1-deficient bone-marrow derived macrophages (BMDMs), using high throughput sequencing (RNA-seq, ChIP-seq, ATAC-seq and Capture-Hi-C).

first: Dora

last: Bojcsuk

first: Petros

last: Tzerpos


title: The Heme-regulated transcriptional repressor, BACH1 safeguards macrophage enhancer selection, activation andtissue adaptation [RNA-seq_muscle]


title: The Heme-regulated transcriptional repressor, BACH1 safeguards macrophage enhancer selection, activation andtissue adaptation [RNA-seq_BMDM]


title: The Heme-regulated transcriptional repressor, BACH1 safeguards macrophage enhancer selection, activation andtissue adaptation [ATAC-seq_muscle]


title: The Heme-regulated transcriptional repressor, BACH1 safeguards macrophage enhancer selection, activation andtissue adaptation [ATAC-seq_BMDM]


title: The Heme-regulated transcriptional repressor, BACH1 safeguards macrophage enhancer selection, activation andtissue adaptation [ChIP-seq]


title: Gene expression data at the single cell level of human hamstring, deltoid, supraspinatus muscle; as well as, cultured human muscle fibroadipogenic cells (FAPs)

city: San Francisco

first: Steven

middle: Michael

last: Garcia

address: 1700 Owens St.

department: Orthopaedic Surgery

institute: UCSF

summary: Human FAPs are thought to be heterogenous. We utilize 14 unique patient samples to character FAP heterogenity and further analyze FAPs cultured in different media conditions.

overall_design:
Human muscle was mechanically and enzymatically digested, FAPs were sorted by FACS and sequencing along with all muscle cells. Cultured FAP samples were grown in vitro in adipogenic, fibrogenic, and growth media conditions. All cells were analyzed by 10x Genomics 3' single cell RNA sequencing.
The allcells_*  and fapsonly_* files contain integrated data from the following 14 samples, all cells.
The Std_Adipo_TGFB* files contain integrated data from tall 3 cultured FAP samples
***Please note that raw data files for the FAPs* samples have been lost and thus are not provided ****

middle: M

first: Agustin

last: Diaz

first: Justin

last: Lau

first: Hannah

last: Chi

first: Miguel

last: Lizarraga

first: Michael

middle: R

last: Davies

first: Xuhui

last: Liu

first: Brian

middle: T

last: Feeley


title: DOT1L regulates MYC/Mondo turnover on chromatin

city: Boston

first: Boston University

last: Microarray and Sequencing Resource

state: MA

address: 72 East Concord Street, E631

department: Microarray and Sequencing Resource

institute: Boston University

summary: DOT1L is the only known histone 3 lysine 79 methyltransferase in mammals. This methylation mark is found in the gene bodies, promoters, and enhancers of actively transcribed genes and is important for the maintenance of open chromatin structure. DOT1L is recognized as an oncoprotein in numerous cancers. However, our current mechanistic understanding of the oncogenic role of DOT1L is incomplete, with recent studies suggesting that DOT1L can regulate transcription in a methyltransferase-independent manner and can cooperate with c-MYC. Here, we have created a DOT1L/+ knockout MDA-MB-231 breast cancer cell line in which we observe increased accumulation of c-MYC without a corresponding increase in target gene expression. This c-MYC accumulation under global reduction of c-MYC-dependent gene expression suggests that c-Myc promoter binding is insufficient for inducing transcription when DOT1L levels are reduced. We show that DOT1L destabilizes c-MYC and works with the proteasome to activate c-MYC-driven gene transcription. Additionally, we uncover a novel proteolytic activity of DOT1L on c-MYC in vitro that may play a role in c-MYC turnover on chromatin. This novel avenue of c-MYC regulation by DOT1L may lead to the development of new approaches for cancer treatment.

overall_design: WT and DOT1L/+ KO cells were compared for diffrerential gene expression.

first: Gian

middle: P

last: Sepulveda

first: Alla

last: Grishok


title: Transcription factor Satb1 modulates the functionality of peripheral Treg cells

city: Kyoto

first: Wooseok

last: Seo

address: Yoshida-Konoe-cho, Sakyo-ku

institute: Kyoto University Graduate School of Medicine

summary: Transcription factor Satb1 plays important roles in the development of various immune cells. By utilizing genetic tools such as conditional knockout in mice have provided valuable information about its roles in T cell development. For example, CD4-cre transgenic mouse has been extensively used to delete Satb1 gene from T cells. While CD4-cre is useful to knockout a target gene floxed by LoxP sites from T cells, its expression lacks tissue specificity. To decipher the specific roles of Satb1 in T cells, we generated Satb1 conditional knockout mice with ThPOK-cre and E8I-cre to delete Satb1 from peripheral CD4+ and CD8+ T cells, respectively. Subsequently, total RNA-seq was performed to examine changes in transcriptome in the absence of Satb1 from peripheral T cells.

overall_design: Total RNA-seq analysis of perihperal Treg cells from Satb1 F/F; ThPOK-cre; FoxP3-Gfp.

first: Ichiro

last: Taniuchi


title: Transcription factor Satb1 modulates the functionality of in vitro stimulated CD8+ T cells

overall_design: Total RNA-seq analysis of in vitro cultured CD8+ T cells from Satb1 F/F; E8I-cre.


title: Transcriptomic Signatures Associated With Amelioration Of Radiation Induced Gastrointestinal Mucositis By Compound Kushen Extracts

status: Public on Jul 12 2026

city: Adelaide

first: Yan

last: Zhou

state: South Australia

address: 108 North Terrace

department: Biological science

country: Australia

institute: Adelaide University

summary:
Introduction: Radiation-induced gastrointestinal mucositis (GIM) is a severe complication of radiotherapy that compromises patient quality of life and treatment efficacy. Compound Kushen Injection (Fufang Kushen Zhusheye, CKI), comprising Radix Sophorae Flavescentis (Kushen) and Rhizoma Smilacis Glabrae (Baituling), is widely used as an adjuvant medicine in the treatment of cancer for pain relief and reduction of cancer therapy side effects. This study assessed the therapeutic potential and explored the associated transcriptomic changes of CKI and its powder form, Compound Kushen Powder (CKP), in alleviating GIM.
Methods: Both drugs were evaluated in a rat model of radiation-induced GIM. Following irradiation and administration of either CKP or CKI, transcriptomic analysis of the jejunum and colon mucosa was performed to identify potential biological pathways and generate hypotheses regarding their mode of action.
Results: Administration of either CKP or CKI to irradiated rats significantly reduced the severity of GIM symptoms. Transcriptomic profiling identified both shared and distinct pathways affected by the treatments. The transcriptomic profile of CKP-treated tissues showed enrichment in gene sets related to innate immune activation and inflammatory signalling, affecting genes such as Socs3 and Tlr4. Conversely, CKI treatment was associated with tissue repair and oxidative stress resistance through genes including Osm, Epha2, and Stat3. Both forms of the herbal extract correlated with an upregulated stress response and stimulus regulation in the GIM model.
Discussion: These findings highlight overlapping transcriptomic changes for CKP and CKI, suggesting potential shared pathways associated with symptom suppression in radiation-induced GIM, along with extract-specific associations on distinct pathways acting on different sets of genes. This provides molecular insights to guide future studies into the distinct and overlapping therapeutic usages of these medicines.

overall_design: RNA-seq was performed on colon and jejunum epithelial tissues collected from irradiated Sprague Dawley rats treated with compound Kushen injection, compound Kushen powder, or vehicle controls. Samples were collected at day 4 and day 7 after irradiation. Biological replicates were included for each tissue, treatment, and time-point group.

first: Yuka

last: Harata-Lee

first: David

middle: L

last: Adelson


title: Transcription factor Satb1 modulates the functionality of peripheral T cells

overall_design: Total RNA-seq analysis of peripheral T cells from Satb1 F/F; ThPOK-cre and Satb1 F/F; E8I-cre mice.


title: Single-cell transcriptomic profiling of mouse kidneys in contrast-induced acute kidney injury

city: Nanjing

first: Mengqing

last: Ma

state: Jiangsu

address: 68 Changle Road

institute: Nanjing First Hospital, Nanjing Medical University

summary: This study generated single-cell RNA sequencing profiles from four mouse kidneys with contrast-induced acute kidney injury (CIAKI) using the 10x Genomics Chromium platform. The dataset was generated to characterize renal cell populations, cell type-specific transcriptional alterations, and immune responses associated with CIAKI. It provides a comprehensive resource for investigating the molecular mechanisms underlying kidney injury and related cellular responses.

overall_design: Four mouse kidney samples were collected after contrast-induced acute kidney injury (CIAKI) induction and processed for single-cell RNA-seq using the 10x Genomics platform. The four CIAKI samples were analyzed as independent biological replicates to investigate renal cell composition and cell-type-specific transcriptional changes associated with CIAKI.

first: Hao

last: Zhang

first: Weijuan

last: Deng

first: Xia

last: Du

first: Ting

last: Chen

first: Zhaowei

last: Wang

first: Chuxian

first: Mengxing

first: Binbin

last: Pan

first: Dawei

first: Qing

last: Sun

first: Mengting

last: Lu

first: Yimin

last: Li

first: Wenjuan

last: Huang

first: Rui

last: Tang

first: Zhibin

last: Qiu

first: Xin

last: Wan

first: Changchun

last: Cao


title: STING Drives CD4+T Cell Differentiation via JAK-STAT Signaling in Bullous Pemphigoid

city: Tianjin

first: Weiwei

last: Jiang

address: No. 354, Beima Road, Hongqiao District, Tianjin

department: Dermatology

institute: Tianjin Academy of Traditional Chinese Medicine Affiliated Hospital

summary: Bullous pemphigoid (BP) is an autoimmune blistering disease with an increasing incidence in recent years; however, the underlying immune regulatory mechanisms remain largely unclear. As a critical signaling hub linking innate and adaptive immunity, stimulator of interferon genes (STING) has recently been implicated in the pathogenesis of various autoimmune diseases and may regulate tissue inflammation and immune homeostasis through modulation of CD4+ T cell responses. In this study, transcriptomic analysis revealed that differentially expressed genes in peripheral blood CD4+ T cells from BP patients were primarily enriched in the JAK-STAT signaling pathway, T cell activation and differentiation, and type I interferon (IFN-I)-related pathways. Pharmacological inhibition of STING markedly attenuated the aberrant activation of these signaling pathways. Our findings suggest that STING may contribute to BP immunopathogenesis by regulating the JAK-STAT signaling axis and promoting abnormal CD4+ T cell activation and differentiation, providing new insights into the molecular mechanisms underlying BP and identifying potential therapeutic targets.

overall_design: RNA-seq profiling of the cultured CD4+ T cells collected from 3 patients with BP and 3 healthy controls (HC), with or without STING inhibitor C176 5μM treatment for 24h.

first: Mengke

first: Junchen

last: He

first: Tianxue

first: Tao

last: Guo

first: Lizhi

last: Hu


title: The impact of PAX5 overexpression on gene expression profile in PC-9 cells

city: hangzhou

first: ailing

last: wu

address: yuhangtang street

institute: hangzhou normal university

summary: PAX5, a transcription factor, is expressed exclusively in pro B cells. To understand the genes regulated by PAX5 in NSCLC cells, we overexpressed PAX5 in PC-9 cells and examined the change of transcription profile.

overall_design: PC-9 cells were divided into two groups: a vehicle control group and a PAX5 overexpressed group. Each group consisted of three biologically independent replicates. Following the treatment, total RNA was isolated from all samples. The integrity and quantity of the RNA were verified. Subsequently, RNA-seq libraries were constructed from the high-quality RNA and sequenced on an Illumina platform to generate transcriptome profiles for subsequent analysis.


title: Distinct macroH2A variant dynamics reveal temporal mH2A2 displacement at cell-cycle regulatory elements

city: Minhang

first: deng

last: yongzhuo

state: Shanghai

address: DongchuanoRoad N0.800

institute: Shanghai Jiao Tong University

summary: MacroH2A (mH2A) variants have traditionally been viewed as transcriptional repressors, with mH2A2 specifically implicated in modulating enhancer accessibility to suppress transcriptional programs. While mH2A1 has been reported to undergo cell-cycle dependent deposition, whether mH2A2 displays similar behavior remains largely unknown. Here, using native ChIP-seq in synchronized Huh-7 cells, we profiled both mH2A1 and mH2A2 across G1/S and G2/M states. We found that although the enriched domains of two mH2A variants overlapped extensively across the genome, their local enrichment patterns diverged substantially, particularly at gene bodies. mH2A2 domains were largely stable across the cell-cycle, yet a small subset displayed phase-specific deposition and displacement. Based on the mH2A2 deposition levels across the cell-cycle, we classified mH2A2 domains into five categories: invariant, G1/S-higher, G1/S-unique, G2/M-higher, and G2/M-unique. Among them, G1/S-unique mH2A2 domains were specifically enriched in the active A compartment, and the potential regulatory elements within them exhibited lower chromatin accessibility. These sites were preferentially bound by cell-cycle regulatory factors and were linked to genes involved in mitotic progression. Collectively, our findings reveal that mH2A2 undergoes selective displacement from regulatory elements during mitotic entry, supporting a model in which mH2A2 functions as a context-dependent regulator of chromatin accessibility during cell-cycle progression.

overall_design: Comparison genome-wide deposition patterns of native ChIP-seq data for mH2A1 and mH2A2 in synchronized Huh-7 cells at G1/S and G2/M phases

first: Yongzhuo

last: Deng

first: Zeqian

last: Xu

first: Jinling

last: Liu

first: Zhifeng

last: Shao

first: Xinhui


title: Overlapped transcription targets of cGAS and JunB in MDA-MB-231 cells

city: Chapel Hill

first: Pengda

state: NC

address: 21-246 Lineberger Building, 450 West Drive, CB7295 450 West Drive, CB7295

department: Biochemistry and Biophysics

institute: The University of North Carolina at Chapel Hill

summary: In addition to serving as a cytosolic dsDNA sensor, we found cGAS also participates into transcriptional control on chromatin independent of nucleosomal binding. cGAS is recruited to chromatin by AP-1 factors such as JunB. The goal of this analysis is to determine the common transcriptional targets co-regulated by cGAS and JunB in MDA-MB-231 cells.

overall_design: MDA-MB-231-cGAS-KO+WT-cGAS, MDA-MB-231-cGAS-KO+F491AF503A-cGAS and MDA-MB-231-cGAS-KO+WT-cGAS+shJunB cells in biological triplicates were used for bulk-RNA-Seq analysis.

first: Deng

last: Yu


title: Pitx2-associated early-onset glaucoma alters corneal innervation and sensory function in a sex-specific manner [RNA-Seq cornea]

city: Montpellier

first: Frederic

last: Michon

state: non-US Resident

address: Institute for Neurosciences of Montpellier, 80, rue Augustin Fliche

country: France

institute: Inserm - U1298

summary: Purpose: Pitx2-associated developmental glaucoma is characterized by anterior segment dysgenesis, ocular hypertension, and optic neuropathy. Its consequences for corneal sensory innervation remain poorly understood. We investigated whether this disease alters corneal nerve structure and sensory function in a sex-dependent manner. Methods: Male and female Pitx2egl1/egl1 and Pitx2+/+ mice were examined at 1 and 3 months. Ocular phenotyping included intraocular pressure, fundus imaging, visual evoked potentials, and optic nerve ultrastructure. RNA sequencing of corneas and trigeminal ganglia was performed at 3 months. Corneal innervation was assessed by βIII-tubulin immunofluorescence and volumetric quantification of nerve fibers. Corneal sensitivity was measured using Von Frey filaments. Results: Pitx2egl1/egl1 mice developed progressive ocular hypertension, fundus abnormalities, reduced visual evoked potential amplitudes, and optic nerve degeneration, supporting the model as early-onset glaucoma. Baseline sex-related transcriptional differences were limited in both cornea and trigeminal ganglia. In contrast, Pitx2 mutation induced sex-dependent molecular responses. Female corneas showed broader transcriptional changes enriched in inflammatory, stress-response, and tissue-remodeling pathways, whereas male corneas showed a more restricted response involving metabolic and homeostatic processes. Similar sex divergence was observed in trigeminal ganglia. Corneal nerve fiber volume was reduced in both sexes at 3 months but not at 1 month, whereas reduced sensitivity was detected only in mutant males. Conclusions: This study identifies corneal denervation as a component of Pitx2-associated developmental glaucoma. These findings suggest that glaucoma may affect the corneal sensory system beyond optic nerve pathology, highlighting a potentially overlooked dimension of disease relevant to ocular surface monitoring and patient management.

overall_design: RNA-Seq profiling of cornea and trigeminal ganglion of Pax6+/+ and Pax6+/- at 12 weeks of age

first: Solange

last: Sarkis


title: Pitx2-associated early-onset glaucoma alters corneal innervation and sensory function in a sex-specific manner [RNA-Seq Trigeminal Ganglion]

department: Institute for Neurosciences of Montpellier


title: Pannexin 1 phosphorylation sites differentially modulate channel activity and physiological outcomes

city: Charlottesville

first: Brooke

last: O'Donnell

state: Virginia

address: 409 Lane Rd.

department: Robert M. Berne Cardiovascular Research Center

institute: University of Virginia

summary: Within the vasculature, pannexin 1 (PANX1) channels in smooth muscle cells (SMCs) regulate α-adrenergic constriction and blood pressure. PANX1 channel activity is regulated by phosphorylation at Y198, S205 and Y308 residues, but the physiological significance of these modifications is unknown. Here we utilize newly developed PANX1 Y198F, S205A and Y308F phospho-dead mutant mice to test physiological changes related to hemodynamics. Radiotelemetry-measured blood pressure was decreased in Y198F, increased in Y308F, but unchanged in S205A mice at baseline. During sympathetic-driven hypertension, only Y198F mice showed decreases in blood pressure, with reductions resembling control mice treated with the sympathetic inhibitor clonidine. Pressure myography revealed α-adrenergic contractile responses were decreased in Y198F, slightly enhanced in Y308F, but unchanged in S205A third-order mesenteric arteries; with Y198F responses mimicking control vessels treated with PANX1 inhibitors. To understand signaling changes driving these phenotypes, we performed mesenteric artery bulk RNA sequencing but found a minimal number of differentially expressed genes between phospho-dead mutant and controls. Similarly, co-immunoprecipitation-mass spectrometry of wildtype or phospho-dead mutant-expressing vascular SMCs revealed few interacting proteins distinct to each PANX1 variant. However, PANX1 channel activity assessments in HEK293T cells expressing the α1D-adrenergic receptor and each phospho-dead mutant PANX1 showed phenylephrine-induced ATP release from Y198F channels was significantly decreased compared to wildtype, but current was unaffected. Conversely, S205A and Y308F ion flux was reduced, with ATP release resembling controls. Taken together, these findings demonstrate that physiological outcomes are regulated by distinct PANX1 metabolite versus current conducting properties, which are ultimately controlled by PANX1 phosphorylation.

overall_design: Bulk RNA sequencing was performed on RNA isolated from PANX1 Y198F, S205A, Y308F and global Panx1 KO mesenteric arteries (three vascular trees each) and corresponding littermate or WT controls. RNA was isolated from mesenteric arteries using the RNeasy MinElute Cleanup Kit (QIAGEN, #74204) from male mice at 8 weeks of age. Paired-end 150 base pair reads were generated using the Illumina NovoSeq platform and mapped to the Genome Reference Consortium Mouse Build 39 (GRCm39; Accession ID GCA_000001635.9) reference genome using STAR software (v2.7.9a). In RStudio (v4.4.2), gene counts were generated using featureCounts in the Rsubread (v2.20.0) software package. Differentially expressed genes (DEGs, Padj < 0.05) were identified using DESeq2 (v1.46.0), and the org.Mm.eg.db package was used to convert Ensemble IDs to gene symbols.

first: Luke

middle: S

last: Dunaway

first: Brant

middle: E

last: Isakson


title: Transcriptomic analysis of functional versus desensitized natural killer cells

city: Berkeley

first: Yeara

last: Jo

address: 485 Weill Hall

institute: University of California, Berkeley

summary: Natural Killer (NK) cell desensitization induced by persistent stimulation limits durable antitumor immunity, yet the molecular mechanisms governing this dysfunctional state remain poorly defined. To identify conserved regulators of NK cell desensitization, we performed comparative transcriptomic analyses across multiple murine models of persistent activation and dysfunction. We set up multiple robust in vivo and in vitro conditions to compare desensitized NK cells with their functional counterparts. First, we compared functional vs. desensitized NK cells that naturally arise through NK cell education. Normal lymphoid cells lacking MHC I are killed by NK cells, indicating that healthy cells provide stimulatory signals that are normally counterbalanced by inhibitory receptors recognizing self MHC I molecules, such as Kb and Db in C57BL6/J (B6) mice. In B6 mice, these receptors include Ly49C and Ly49I (bind to Kb), and CD94/NKG2A (binds to a Db-derived peptide presented by the Qa-1 nonclassical MHC I molecule). Individual NK cells can express any combination of Ly49C, Ly49I or CD94/NKG2A (abbreviated C, I and N, respectively), or none of them. In B6 mice, NK cells lacking all 3 receptors (C-I-N- NK cells; triple negative, TN) are inhibited the least and therefore persistently stimulated the most by neighboring cells in steady state conditions, resulting in a high degree of desensitization. NK cells expressing only one of the receptors, such as Ly49I+ single positive (SP) cells, are only partially inhibited and therefore less desensitized, and triple positive (TP) NK cells are inhibited the most and therefore least desensitized. Consequently, in response to activating receptor engagement ex vivo, the degranulation and cytokine production responses follow the pattern TP>SP>TN. The same pattern held when we gated on the most mature, CD27-CD11b+ NK cell subset. In MHC I-deficient B2m–/– mice, all NK cells are persistently stimulated and therefore strongly desensitized, similar to TN cells in B6 mice. We next established additional modes of desensitization, including 22-hour stimulation with ionomycin, a calcium ionophore that mimics receptor-induced Ca2+ influx and is known to induce a state of dysfunction in both T cells and NK cells. We confirmed that a 22-hour treatment with ionomycin desensitized murine NK cells. As yet another mode of desensitization, we reproduced persistent ‘induced self’ signals by simultaneously stimulating normal NK cells in vitro via engagement of multiple activating receptors for an extended period. NK cells were desensitized by stimulation for 48-hours with plate-bound antibodies targeting NKp46 in combination with NKG2D or DNAM-1, combinations that optimally activate NK cells. We performed bulk RNA-seq to compare desensitized NK cells and their functional counterparts in the aforementioned conditions: 1) SP vs. TP, TN vs. TP, or TN vs. SP NK cells in B2m+/+ mice (labeled "CIN"), 2) TP NK cells from B2m–/– vs. B2m+/+ mice (B2m), 3) NK cells treated with ionomycin vs. vehicle (iono), and 4) NK cells stimulated for 48 hours with combinations of activating receptor antibodies (Ab combo). Furthermore, in MHC I-deficient tumors, NK cells initially recognize the loss of MHC I and attack tumor cells, such that small tumor loads can be eradicated, but with larger tumor loads NK cells eventually become desensitized and lose the capacity to control the tumors. We further provide gene expression profiles of NK cells isolated from MC38-B2m–/– colorectal tumors as a representation of such case.

overall_design: RNA-seq profiling of CD27-CD11b+ Ly49C+Ly49I+NKG2A+ (TP), Ly49C-Ly49I+NKG2A- (SP), Ly49C-Ly49I-NKG2A- (TN) NK cells from WT (B2m+/+, C57BL/6 (B6)) and B2m-/- mice, NK cells isolated from splenocytes treated for 22 hours with vehicle or ionomycin, NK cells isolated from splenocytes left in medium or stimulated with plate-bound anti-NKp46+anti-NKG2D antibodies or anti-NKp46+DNAM-1 antibodies for 48 hours, or CD27-CD11b+ NK cells isolated from B6 mice subcutaneously inoculated with 4E6 MC38 B2m-/- cells for 10 days.

first: David

middle: H

last: Raulet


title: Kabuki syndrome type I fibroblast multi-omics dataset: bulk RNA-seq profiles from primary skin fibroblasts

city: Napoli

first: Emile

last: Danvin

state: NAPOLI

address: Sergio pansini 5

department: Molecular medicine

country: Italy

institute: Federico II University of Naples

summary: Kabuki syndrome type 1 (KS1) is a rare congenital disorder caused by heterozygous loss-of-function mutations in KMT2D – an H3K4 histone methyltransferase. While KMT2D function during early development is increasingly understood, the transcriptional and chromatin accessibility consequences of its loss in differentiated somatic tissues remain poorly characterized. We present a multi-omic dataset from primary dermal fibroblasts of seven individuals with KS type I and nine unaffected donors. The dataset comprises bulk RNA-seq from sixteen donors (nineteen libraries across two sequencing batches, including three donors sequenced in both batches to assess technical replicability) and ATAC-seq from ten donors (six KS, four controls). All libraries were processed through standardized nf-core pipelines, with differential analyses performed using DESeq2 with RUVSeq batch correction. This resource is intended to facilitate research on Kabuki syndrome type 1 and by expanding the available models for studying the group of mendelian disorders known as chromatinopathies.

overall_design: experimental design: Bulk RNA-seq comparing KS type I patient-derived fibroblasts versus control fibroblasts. Samples sequenced across two batches (84, 185) with technical replicates for batch effect assessment.

first: Paolo

last: Salerno

first: Eleonora

last: Di Venere

first: Gabriella

last: Squeo

first: Dario

last: Righelli

first: Giuseppe

last: Merla


title: Kabuki syndrome type I fibroblast multi-omics dataset:  ATAC-seq profiles from primary skin fibroblasts


title: High intrinsic aerobic capacity shapes a distinct epigenetic profile in the aged rat brain

city: Budapest

first: Zsolt

last: Radák

address: Budapest, Alkotás u. 42-48, 1123

department: Research Center for Molecular Exercise Science

institute: University of sports science, Hungary

type: Methylation profiling by high throughput sequencing

summary: Aging is accompanied by progressive decline in brain function, and aerobic fitness is thought to influence brain health. To examine whether intrinsic exercise capacity is associated with a distinct brain molecular phenotype in aging, we profiled hippocampal DNA methylation by reduced representation bisulfite sequencing (RRBS) in aged selectively bred rats with high or low intrinsic aerobic capacity.

overall_design: Hippocampal genomic DNA from aged female selectively bred high-capacity runner (HCR) and low-capacity runner (LCR) rats was profiled by reduced representation bisulfite sequencing (RRBS).

first: Lei

last: Zhou

first: Radak

last: Zsolt


title: Pooled combinatorial screening identifies transcription factor sets that drive hematopoietic progenitor-like cell fate

city: Cambridge

first: James

last: Briggs

address: 75 Ames St

institute: Broad Institute

summary: Mammalian cells can be directed towards specific fates by overexpression of transcription factors (TFs). However, discovering and optimizing which TFs in combination produce a state of interest remains challenging. Here, we develop a scalable screening platform that addresses this challenge by combining high-MOI pooled delivery of barcoded TF ORFs, data augmentation, targeted cell enrichments, and single-cell transcriptomic readouts. As proof of principle, we apply the platform to optimize the generation of hematopoietic stem and progenitor-like cells (HSPCs) from human embryonic stem cells. Our data demonstrate technical performance across a range of key metrics and reveal a richly structured reprogramming fitness landscape over millions of TF combinations. In silico optimization of HSPC-similarity metrics over this landscape revealed two TF combinations that demonstrate superior potency in generating naïve multipotent hematopoietic progenitors relative to gold-standard controls. This study demonstrates a powerful approach for data-driven cell fate engineering using complex combinatorial perturbations.

overall_design: Pooled TF overexpression screen in H1 embryonic stem cells with: scRNA-seq phenotype readout, perturbation identification by sequenced barcodes, and enrichments for hematopoietic fate outcomes.

first: Janghwan

last: Cho

first: Daniel

last: Strebinger

first: Julia

last: Joung

first: Tatum

last: Braun

first: Rhiannon

last: Macrae

first: Hojun

last: Li

first: Feng

last: Zhang


title: PGK1 acts as a non-catalytic gatekeeper of ferroptosis by stabilizing SLC7A11 [scRNA-seq]

city: ChongQing

first: yuanze

last: zhou

address: No.30, Gaotanyan Main Street, Shapingba District

institute: The First Hospital Affiliated to Army Medical University (Southwest Hospital)

summary: Comparative gene expression profiling analysis of scRNA-seq data for PGK1 KO and PGK1 WT HCC cells

overall_design: PGK1 KO or PGK1 WT Hepa1-6 cells (5 × 10⁶) were  injected into the subcapsular space of the left lateral liver lobe. Four weeks after implantation, mice were euthanized; livers were excised and collected, and fresh tumor tissue were  minced into small pieces, and dissociated for scRNA seq assay.

first: Guixian

last: Wu

first: Yuanze

first: Chengxin

last: Luo

first: Yaqun

last: Ding

first: Xi

first: Hui

first: Shuangnian

last: Xu


title: PGK1 acts as a non-catalytic gatekeeper of ferroptosis by stabilizing SLC7A11

address: No.30 Gaotanyan Main Street District

institute: Southwest Hospital, Third Military Medical University

summary: Ferroptosis is restrained by layered antioxidant defenses, yet whether glycolytic enzymes directly constitute ferroptosis-defense machinery remains unclear. Here we identify phosphoglycerate kinase 1 (PGK1) as a non-canonical suppressor of ferroptosis that functions independently of its glycolytic kinase activity. Across pan-cancer bulk and single-cell transcriptomes, glycolysis inversely associates with ferroptosis programs, with PGK1 emerging as a prognostic hub. PGK1 loss in multiple tumor models elicits hallmark ferroptotic features, elevates lipid peroxidation and labile iron, and suppresses xenograft growth, all of which are reversed by liproxstatin-1. Mechanistically, PGK1 physically binds the C-terminal tail of SLC7A11 (aa 471-501) and shields it from ubiquitin-proteasome degradation, thereby sustaining cystine-driven glutathione synthesis and redox homeostasis. This scaffolding role is preserved in a kinase-dead PGK1 mutant, establishing a strict separation between metabolic and ferroptosis-regulatory functions. Restoring SLC7A11 rescues PGK1-deficient tumor growth, whereas a rationally designed competing peptide SLC7A11471-501 (FP-01) disrupts the PGK1-SLC7A11 interface, depletes SLC7A11/GSH, triggers ferroptosis, and suppresses tumor progression in vivo. Collectively, the PGK1-SLC7A11 interaction represents a druggable ferroptosis vulnerability that enables selective ferroptosis induction while sparing essential glycolysis.

overall_design: To investigate the function of PGK1 in HT1080 cell, we knockout PGK1 gene by CRISPR cas9.


title: Transcriptome datasets of spleen tissues during hibernating and active states in the greater horseshoe bat (Rhinolophus ferrumequinum)

city: Shenyang

first: Wanyi

last: Dang

state: Liaoning

address: 120 Dongling Rd, Shenyang, China

institute: Shenyang Agricultural University

summary: Hibernation is a complex physiological response for animals to adapt to extreme environmental conditions, which can affect the functions of immune organs such as the spleen. We used comparative transcriptomics to study functional changes of the spleen during hibernating and active states by comparing transcriptomes generated from spleens of four physiological states (Summer Active, Torpor, Arousal and Winter Active) in the greater horseshoe bat.

overall_design: Gene expression profiling of entire spleen tissues in the wild female greater horseshoe bat at Summer Active (July), Torpor (November), Arousal (November, captured for 2 h) and Winter Active (November, captured for 26 h) states, each with two biological replicates.

first: Junpeng

first: Yanlei

last: Liu

first: Wei

last: Teng

first: Shuyi

first: Huiling

last: Xue

first: Zhe

last: Wang


title: The novel nano-selenium supplement extends lifespan and delays multi-organs aging by regulating the Sik1 pathway through maintaining calcium homeostasis

first: Jintao

last: Song

address: No. 77, Puhe Road

institute: China Medical University

summary: Aging involves progressive physiological decline and increased disease susceptibility, creating demand for effective interventions. While selenium regulates redox homeostasis and aging, its therapeutic use is limited by bioavailability and toxicity. We developed diselenide-bridged mesoporous silica nanoparticles (SeMSNs) as a novel delivery system. SeMSNs delayed cellular senescence in fibroblasts and H₂O₂-induced models by reducing oxidative stress and senescence markers (p16, p21). In aged mice, SeMSNs extended lifespan, reduced frailty, and improved multiple age-related conditions including muscle atrophy, renal dysfunction, cognitive decline, and hepatic steatosis while restoring metabolic balance. Mechanistically, SeMSNs upregulated selenoproteins (GPx1, SelK), restored calcium homeostasis, attenuated ER stress, and inhibited NFATc2-mediated Sik1 transcription. Clinical data showed inverse correlations between selenium levels and aging biomarkers. SeMSNs also rejuvenated human adipose progenitor cells via calcium-NFATc2-Sik1 modulation. These findings reveal SeMSNs surpass conventional antioxidants by targeting selenium-calcium crosstalk, providing a translatable nanotherapeutic strategy for multi-organs aging intervention and healthy longevity through selenium's molecular mechanisms.

overall_design: Eighteen-month-old wild-type male C57BL/6 mice were selected. The experiment was divided into one experimental group and one control group, with 6 to 10 mice in each group. The mice in the experimental group were given SeMSNs at a concentration of 1 mg/mL and a dose of 5 mg/kg body weight, administered twice every two days. The control group mice were given normal diet and an equal amount of normal saline by gavage. At the age of 23 months, the mice were euthanized and their tissues were collected for sequencing.

first: Yang

last: Yu

first: Mengjiao

last: Guo


title: Nicotine and quercetin alleviate ulcerative colitis through inhibition of PI3K/AKT and NF-κB pathways

city: Zhengzhou

first: huanhuan

last: ma

address: Cuizhu street

institute: china tobacco quality supervision and test center

summary: Ulcerative colitis (UC) remains a therapeutic challenge due to its chronicity, adverse effects of current drugs, and high relapse rates. Smoking inversely correlates with UC risk. Nicotine (NIC) shows UC efficacy but causes non-smoker intolerance. Bioinformatic identification of tobacco-derived quercetin (QUE), an α7 nAChR enhancer, suggests its potential as a NIC synergist for reduced side effects. We thus hypothesized that half-dose NIC-QUE co-therapy would exert superior anti-colitis effects. Using a DSS-induced murine colitis model, we performed a multidimensional assessment spanning: Clinical phenotypes (body weight, disease activity index (DAI), colon length, histopathology), Gut microenvironment (gut microbiota composition, short-chain fatty acids (SCFAs) and barrier integrity) and Inflammatory mechanisms (inflammatory cytokines and signaling pathways). The half-dose NIC-QUE combination almost outperformed monotherapies across all dimensions, such as body weight, DAI, colon length, histopathology. Mechanistically, synergy arose from: the synergistic effect involved: reshaping gut microbiota structure (notably increasing Clostridia and Eubacterium while reducing Erysipelotrichia), restoring key SCFA levels (acetate, butyrate, propionate, valerate), enhancing intestinal barrier integrity (ZO-1, Muc2), and critically, suppressing the activation of the PI3K/AKT and NF-κB signaling pathways. To our knowledge, this is the first study demonstrating that half-dose NIC-QUE co-administration constitutes a novel UC therapeutic strategy. Its core mechanism involves coordinated restoration of the gut microbiome-metabolite barrier and suppression of the PI3K/AKT/NF-κB inflammatory cascade

overall_design: To investigate the potential mechanism of nicotine and quercetin on alleviating DSS-induced UC mice, we performed RNA-seq analysis on colonic tissues among the CON group, DSS model group, and NIC and QUE group.

first: hongjuan

last: wang

first: huan

last: chen

first: hongwei

last: hou

first: qingyuan

last: hu


title: Exploitation of KAT6A for the treatment of PPP2R1A-mutated cancers

city: Philadelphia

first: Priyankara

middle: J

last: Wickramasinghe

state: PA

address: 3601 Spruce Street

department: Bioinformatics

institute: The Wistar Institute

summary: PPP2R1A, encoding a subunit of the protein phosphatase 2A (PP2A) enzyme, is mutated in >1% of cases across diverse human cancer types 1. Notably, PPP2R1A mutations are often observed in gynecological cancers 1. To date, clinically applicable therapy based on PPP2R1A mutational status with a durable outcome has not been described. Here we show that inhibition of the KAT6A acetyltransferase induces senescence of PPP2R1A-mutated cancer cells and that PPP2R1A mutational status correlated with response to the KAT6A inhibitors. Mechanistically, mutant PPP2R1A creates KAT6A dependence by regulating transcription of the ubiquitin E3 ligase SKP2 to suppress senescence via degrading p27. Notably, KAT6A inhibition in combination with senolytics such as ABT263 that trigger apoptosis of senescent cells regressed PPP2R1A-mutated tumors. In addition, KAT6A inhibition synergized with immune checkpoint blockade to eradicate PPP2R1A-mutated tumors in vivo. Our data indicate that pharmacological inhibition of KAT6A alone or in combination with senolytics or immune checkpoint blockades represents effective therapeutic strategies for cancers involving PPP2R1A mutations.

overall_design: RNA-seq in a context of PPP2R1A mutation, and KAT6A activity

first: Mitsutake

last: Yano

first: Rugang

last: Zhang


title: Skeletal muscle from CaMKII knockout mice subjected to endurance training

city: Hiroshima

first: Yasuo

last: Kitajima

state: Hiroshima

address: 1-2-3 Kasumi, Minami-ku

institute: Hiroshima University

summary:
Abstract
Background
Calcium/calmodulin-dependent protein kinase II (CaMKII) is activated in skeletal muscle with exercise, yet its physiological role in endurance training adaptation remains unclear. This study determined whether endogenous CaMKIIγ/δ in skeletal muscle is required for endurance training–induced metabolic remodeling and exercise adaptation.
Methods
We generated male skeletal muscle-specific CaMKIIγ/δ knockout (CaMKII mKO) mice and assessed muscle phenotype, exercise capacity, and training adaptation. Acute exercise–induced CaMKII activation was evaluated by phosphorylation status. Transcriptomic changes were analyzed by RNA sequencing before and after 4 weeks of treadmill endurance training. Mitochondrial protein abundance, ultrastructure, and bioenergetics were examined by immunoblotting, transmission electron microscopy, and Seahorse extracellular flux analysis in myotubes with acute CaMKIIγ/δ deletion.
Results
Acute treadmill exercise induced CaMKII phosphorylation in muscle without altering total CaMKII abundance. CaMKII mKO mice showed normal muscle mass, grip strength, and baseline performance. However, endurance training–induced improvement in running capacity was significantly blunted. Transcriptomic analyses revealed downregulation of oxidative phosphorylation and glycolytic gene programs in CaMKII-deficient muscle at baseline and after training. OXPHOS complex protein abundance was partially reduced at baseline and markedly reduced across complexes I-V after training. CaMKII deficiency increased ultrastructurally abnormal mitochondria without reducing mitochondrial number. Consistently, CaMKII-deficient myotubes showed lower absolute per-well oxygen consumption and extracellular acidification rates.
Conclusion
In male mice, endogenous CaMKIIγ/δ in muscle is dispensable for baseline locomotor performance but essential for endurance training-induced metabolic remodeling and mitochondrial integrity. These findings support a role for CaMKII in linking contraction-induced calcium signaling to metabolic adaptation in muscle.

overall_design: RNA-seq analysis of skeletal muscle from control and skeletal muscle-specific CaMKIIγ/δ knockout mice before and after 4 weeks of endurance training


title: Transcriptomic profiling of MIA PaCa-2 cells treated with hydroxyprogesterone caproate

status: Public on Jul 11 2026

city: Shanghai

first: Jinyuan

last: Lu

state: Select

address: No. 325 Guhe Road, Yangpu District, Shanghai

institute: Naval Medical University

summary: Pancreatic ductal adenocarcinoma (PDAC) remains refractory to targeted therapy. This RNA-sequencing study characterizes transcriptional changes in the human PDAC cell line MIA PaCa-2 following treatment with hydroxyprogesterone caproate (HPC). Comparison with DMSO vehicle-treated cells was used to identify HPC-responsive genes and pathways. The transcriptomic analysis supported repression of cell-cycle, DNA-replication and pyrimidine-metabolism programs and contributed to investigation of the COP1-CEBPB-CDA mechanism underlying the anti-PDAC activity of HPC.

overall_design: MIA PaCa-2 cells were assigned to two conditions: DMSO vehicle control and 10 μM hydroxyprogesterone caproate (HPC). Cells were incubated at 37 °C with 5% CO2 for 24 h before RNA extraction and mRNA sequencing. Five biological replicates were analyzed for each condition.

first: Weishan

last: Liang

first: Saisai

last: Tian

first: Yiwen

last: Shen


title: Benchmarking cell-type deconvolution in cross-platform transcriptomic data [Visium]

city: Frankfurt am Main

first: Katharina

last: Imkeller

address: Heinrich-Hoffmann-Str. 7

country: Germany

institute: University Hospital Frankfurt

summary: Background: Transcriptomic data from diverse measurement technologies are widely used to study tissue heterogeneity. Cell-type deconvolution, which resolves mixed transcriptomic signals into cellular components, is a key analytical approach. However, achieving accurate deconvolution across platforms remains challenging due to platform-specific experimental and technological biases. Results: We systematically benchmarked deconvolution performance using real-world cross-platform datasets and simulated data modeling distinct technological features. SpatialDecon and cell2location demonstrated the most reliable and consistent performance across both simulated and experimental settings across a broad range of technological biases. Conclusions: Our results highlight how the different deconvolution tools are affected by data properties that depend on technological differences between transcriptomic platforms. Moreover, we provide practical guidelines for selecting computational methods dependent on experimental design for robust deconvolution of cross-platform transcriptomic data.

overall_design:
To explore differences in the cellular composition of tissue profiled on two spatial transcriptomics platforms, Visium and Nanostring, we analyzed 4 brain tumor specimens from the Frankfurt University Cancer Center. Sections from the same tissue specimen were profiled simultaneously on both platforms. Transcriptome profiles of 9 immune aggregates and 4 corresponding tumor-rich regions of interest (ROIs) were measured using the Nanostring GeoMx® Digital Spatial Profiler (DSP) platform with the whole transcriptome atlas (WTA) gene panel. The same 4 tissue specimens were also profiled using the 10x Genomics Visium v2 FFPE WTA assay. Immune and tumor regions were selected based on CD20 gene expression.

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

last: Singh

first: Pinar

last: Cakmak

first: Jennifer

last: Lun

first: Jadranka

last: Macas

first: Jonathan

last: Schupp

first: Karl

last: Plate

first: Yvonne

last: Reiss


title: RNA seq of mouse tissue samples from  AEW animal models : Effect of MMP9 on gene expression.

city: Kaifeng

first: ruizhen

last: wang

address: Jinming Avenue, Kaifeng City, Henan Province

institute: Henan University

summary: In the present study, RNA-seq technique were performed to explore biological significance of MMP9 in the neuro-cutaneous signaling network of chronic itch. We performed high-throughput sequencing of mouse tissue samples from  AEW animal models. The study found that the transcription level of MMP9 was basically unchanged in the AEW model.

overall_design: Mouse  cheek tissue were taken from AEW model mice.The gene expression of these cells were investigated utilizing DNBSeq platform.

first: Ruizhen

last: Wang

first: Jianghui

last: Meng


title: Bulk RNA-sequencing of killifish retina-RPE across aging

city: Los Angeles

first: Matteo

last: Pellegrini

address: 610 Charles Young Drive East

institute: University of California, Los Angeles

summary: Bulk RNA sequencing was performed on retina-retinal pigment epithelium (retina-RPE) tissue collected from male Nothobranchius furzeri (GRZ background) at four ages (1.5, 3.0, 4.5, and 6.0 months). Total RNA was isolated using the RNeasy Plus Micro Kit (QIAGEN), and sequencing libraries were prepared by Azenta using the Illumina Nextera XT Library Preparation Kit followed by sequencing on an Illumina NovaSeq S4 platform. These data were generated to characterize age-associated transcriptomic changes in the retina-RPE and serve as an independent dataset for evaluating the MKMC alignment-free transcriptomic analysis framework.

overall_design: Retina-RPE tissue was collected from three biological replicates of male Nothobranchius furzeri at each of four ages (1.5, 3.0, 4.5, and 6.0 months), for a total of 12 samples. RNA was extracted from each sample independently, libraries were prepared using the Illumina Nextera XT protocol, and paired-end RNA sequencing was performed on an Illumina NovaSeq S4 instrument.

first: Lajoyce

last: Mboning


title: Dysregulated thymus-ovary axis promotes virtual memory T cell polarization to aggravate PCOS pathology

city: Beijing

first: Chenlei

last: Xu

address: No. 38 Xueyuan Road, Haidian District

institute: Peking University

summary: Polycystic ovary syndrome (PCOS) is characterized by androgen excess, ovarian dysfunction and polycystic ovarian morphology and is classically considered as a disorder of the hypothalamic-pituitary-gonadal (HPG) axis. However, whether organs beyond the reproductive endocrine axis contribute to PCOS pathogenesis remains elusive. Herein, we identified a functional thymus-ovary axis involved in PCOS development.

overall_design: Using complementary mouse models, we demonstrated that thymic remodeling occurs early during disease development, preceding the onset of aberrant ovarian pathology. Disruption of thymic function or genetic ablation of adaptive immunity markedly attenuated PCOS-related lesions, indicating a central role for T cells. Mechanistically, CD8⁺ T cells acted as the dominant effector subset, with selective expansion of virtual memory CD8⁺ T (TVM) cells during PCOS progression. These cells preferentially accumulated in reproductive tissues, exacerbated ovarian inflammation and prolonged disease persistence following endocrine challenge. Functionally, adoptive transfer of TVM cells enhanced disease severity, whereas depletion of CD8⁺ T cells or selective restriction of TVM cell polarization by JAK inhibition alleviated PCOS phenotypes.

first: Yaruo

last: Qiu

first: Weixuan

first: Yao

last: Feng

first: Dan

last: Lv


title: IL-33 as a component of NETs mediates CIAKI by promoting ferroptosis in tubular epithelial cells

city: Nanjing

first: Mengqing

last: Ma

address: 68 Changle Road

institute: Nanjing First Hospital, Nanjing Medical University

summary: This study performed bulk RNA-seq on kidney tissues from WT contrast-induced acute kidney injury (CIAKI), PAD4 KO CIAKI, and IL33 KO CIAKI mice. The dataset was generated to investigate the roles of PAD4-dependent neutrophil extracellular traps (NETs) and IL-33 signaling in CIAKI. Transcriptomic comparisons were used to identify gene expression programs and pathways related to NETs activation, IL-33 signaling, and tubular injury.

overall_design: A mouse model of contrast-induced acute kidney injury (CIAKI) was established in WT, PAD4 KO, and IL-33 KO mice. Kidney tissues were collected from two comparison sets: WT CIAKI versus PAD4 KO CIAKI, and WT CIAKI versus IL33 KO CIAKI, with three independent biological replicates per group. Total RNA was extracted from each kidney sample and subjected to bulk RNA-seq to investigate PAD4-dependent neutrophil extracellular traps (NETs), IL-33 signaling, ferroptosis, and tubular injury in CIAKI.

first: Hao

last: Zhang

first: Weijuan

last: Deng

first: Xia

last: Du

first: Ting

last: Chen

first: Zhaowei

first: Chuxian

first: Mengxing

first: Binbin

last: Pan

first: Dawei

first: Qing

last: Sun

first: Mengting

last: Lu

first: Yimin

last: Li

first: Wenjuan

last: Huang

first: Rui

last: Tang

first: Zhibin

first: Xin

last: Wan

first: Changchun

last: Cao


title: Prenatal DBP Exposure Dysregulate Fetal-Placenta Spatial Transcriptomic Profiles

city: Tucson

first: chi

last: zhou

state: AZ

address: 4101 N Campbell Ave, Rm N109, ARC, U of Arizona

department: Animal and Comparative Biomedical Sciences

institute: University of Arizona

summary: Dibutyl phthalate (DBP), a phthalate congener, is widely utilized in consumer products and medication coatings. Women of reproductive age have a significant burden of DBP exposure. Prenatal DBP exposure is associated with adverse pregnancy/fetal outcomes in the offspring. However, the role of fetal sex and the general mechanisms underlying DBP exposure-associated adverse pregnancy outcomes are unclear. This study characterized fetal sex-specific spatial transcriptomic responses in gestational day 18.5 mouse placentas from fetuses with and without prenatal DBP exposure.

overall_design: GD18.5 mice placentas of female and male fetuses from control and DBP exposed animals are included in this study. Control female (CT-F, n=4), control male (CT-M, n=3), DBP exposed female (DBP, n=3), DBP exposed male (DBP-M, n=3). Each placenta from a different dam.

first: Chi

last: Zhou


title: Next generation sequencing facilitates quantitative analysis of transcriptional profiling of  clinical strain Candida albicans CA10 with iravacycline hydrochloride and fluconazole treament alone or in combination.

city: Jinan, Shandong Province

first: yun

middle: xiu

last: li

address: No.238 Jingshi East Road, Jinan City

institute: Shandong Provincial Maternal and Child Health Care Hospital Affiliated to Qingdao University

summary: mRNA profiles of  Candida albicans clinical strain CA10, which treated with iravacycline hydrochloride and fluconazole alone or in combination, were generated by deep sequencing, in triplicate, using Illumina NovaSeq 6000 . The sequence reads that passed quality filters were analyzed at the transcript isoform level. qRT–PCR validation was performed using SYBR Green assay.We found that the gene expression related to purine nucleotide synthesis was significantly down-regulated in the combination group of iravacycline hydrochloride and fluconazole, which suggested that we might have DNA damage.

overall_design: mRNA profiles of  Candida albicans clinical strain CA10 which treated with or without iravacycline hydrochloride and fluconazole alone or in combination were generated by deep sequencing, in triplicate, using Illumina NovaSeq 6000

first: Shicun

last: zheng

first: Xiuyun


title: RNA-seq analysis of thick ascending limb (TAL) epithelium isolated from uromodulin (UMOD) deletion mutation and wild type (WT) kidney organoids with or without mesencephalic astrocyte-derived neurotrophic factor (MANF) overexpression

city: St. Louis

first: Eric

last: Tycksen

state: Missouri

address: 4444 Forest Park Avenue

department: McDonnell Genome Institute

institute: Washington University in St. Louis School of Medicine

summary: Autosomal dominant tubulointerstitial kidney disease due to uromodulin mutations (ADTKD-UMOD) is one of the leading hereditary kidney diseases. Currently there is no targeted treatment. To illuminate human relevance of mesencephalic astrocyte-derived neurotrophic factor (MANF)-based therapy, we have established patient induced pluripotent stem cell (iPSC)-derived kidney organoid model carrying UMOD p.H177-R185del, the leading mutation causing ADTKD. We have discovered that MANF can directly bind and repress ER calcium release channel IP3R1, thus enhancing AMPK-induced autophagy in a TRIB3-dependent manner. The therapeutic implication of this finding may well be extended to other protein misfolding diseases.

overall_design: This study evaluates the therapeutic role of MANF in ADTKD by utilizing iPSC-derived kidney organoids containing from a UMOD DEL/+ patient and an unaffected family member. We employed a doxycycline-inducible system to overexpress MANF and performed RNA-Seq on isolated Thick Ascending Limbs (TALs) across four experimental groups (WT, DEL, WT_MANF, and DEL_MANF; n=3 per group).

first: Maggie

middle: Y


title: Expanding the ASXL1 Mutation Spectrum: Transcriptomic and Metabolic Dysregulation Underlying Overgrowth Phenotype in Inherited ASXL1 Missense Mutations

first: Isabella

last: Lin

address: 615 Charles E Young Dr S

institute: University of California Los Angeles

summary: Mutations in genes associated with chromatin remodeling, such as Additional sex combs-like 1 (ASXL1), underlie a spectrum of congenital abnormalities and neurodevelopmental disorders. Pathogenic variants in ASXL1 are classically associated with Bohring–Opitz syndrome (BOS), a severe developmental disorder caused predominantly by de novo truncating mutations. In this study, we present a 14-year-old female with overgrowth, macrocephaly, and normal neurodevelopment, features that diverge from the typical BOS phenotype. This proband was found to carry a paternally-inherited ASXL1 missense mutation (c.4562C>T p.Ala1521Val) in the plant homeodomain (PHD), a variant of unknown significance (VUS). To investigate its functional impact, we performed integrated transcriptomic (RNA-seq) and metabolomic profiling of peripheral blood and patient-derived fibroblasts, with comparison to unaffected controls and previously characterized BOS samples. Transcriptomic analysis demonstrated that ASXL1 missense carriers exhibit a gene expression profile distinct from BOS. Cross-tissue integration identified 104 shared differentially expressed genes, significantly enriched for oxidative phosphorylation pathways. Notably, mitochondrial genes were downregulated in blood but upregulated in fibroblasts, suggesting tissue-specific metabolic adaptation. Metabolomic profiling revealed depletion of glycolytic intermediates and reduced levels of key energy carriers, including NAD⁺ and NADPH, indicating impaired energy metabolism. In contrast to BOS, which is characterized by transcriptional de-repression and increased glycolytic activity, ASXL1 missense cells demonstrated a predominantly repressive transcriptional profile and diminished bioenergetic capacity. These findings define a distinct molecular and metabolic signature associated with ASXL1 missense variation and support an expanded phenotypic spectrum beyond classical BOS.

overall_design: RNA-seq profiling of affected individuals with ASXL1 missense p.Ala1521Val mutation and familial control blood and fibroblasts.

first: Valerie

last: Arboleda


title: Menin-RelA complex antagonizes cancer cell-intrinsic and tumor microenvironment-induced NF-κB hyperactivation to suppress pancreatic neuroendocrine tumorigenesis

city: Singapore

first: Adrian

middle: Kee Keong

last: Teo

state: Singapore

address: 61 Biopolis Drive, Proteos

department: Stem Cells and Diabetes Laboratory

country: Singapore

institute: IMCB, A*STAR

summary: Pancreatic neuroendocrine tumors (PNETs) are rare neuroendocrine cancers with high mortality rates and an immense unmet medical need. While the genetic and immune landscape of PNETs is defined, the molecular mechanisms linking these factors to tumorigenesis remain poorly understood. Here, we identify NF-κB signaling as a key effector pathway that contributes to PNET tumorigenesis, regulated through both cancer cell extrinsic and intrinsic mechanisms. CellChat analysis identifies M2-like macrophages as the dominant source of NF-κB-activating cytokines, and co-culture of PNET cancer cells with THP-1-derived M2-macrophages significantly enhances RelA phosphorylation and colony-forming capacity in vitro. Concurrently, we uncovered a cancer cell intrinsic safeguard mechanism wherein the tumor suppressor menin physically associates with RelA to suppress PNET growth in vitro and in vivo. Molecular docking identified key residues mediating the menin-RelA interaction and revealed three clinically relevant menin mutants (P320R, R415P, W423R) that destabilize this complex, compromising menin’s ability to restrain PNET growth. Mechanistically, menin and RelA co-bind κB sites on promoters of proliferation-associated NF-κB target genes, including NR4A1, and epigenetically silence their expression through reduced H3K27ac. Crucially, NR4A1 depletion or small-molecule inhibition suppresses PNET growth in vitro and in vivo. Together, our findings reveal a novel menin-RelA-NR4A1 axis that regulates PNET growth and demonstrates how extrinsic and intrinsic factors converge on NF-κB signaling, highlighting potential therapeutic avenues.

overall_design: RelA and H3K27Ac ChIP-seq of QGP-1 control and QGP-1 cells overexpressing menin

first: Claire Wen Ying

last: Neo

first: Jun Wei

last: Chan

first: Elhadi

last: Iich

first: Tomomi

last: Taguchi

first: Nikita

last: Bora

first: Gokce

last: Oguz

first: Si Rong

last: Heng

first: Xinyi

last: Zhang

first: Jet Yee

last: Ng

first: Alvin Wei Tian

first: Kally Sze Mien

last: Tan

first: Wei Xuan

first: Adaikalavan

last: Ramasamy

first: Takeshi

last: Miyatsuka

first: Tatsuya

last: Kin

first: James

last: Shapiro

first: Khek-Yu

last: Ho

first: Joanne Yuen Yie

last: Ngeow

first: Adrian Kee Keong


title: Spermine oxidase promotes oxidative stress during islet inflammation

city: Chicago

first: Sarah

middle: A

last: Tersey

state: IL

institute: University of Chicago

summary: Diabetes is characterized by impaired glucose homeostasis resulting from the dysfunction and loss of insulin-producing islet β cells, with oxidative stress emerging as a central contributor to β-cell injury. The polyamines (putrescine, spermidine, spermine) are known to regulate cellular stress responses, and their metabolism can generate reactive oxygen species (ROS) and reactive aldehydes through catabolic enzymes, including spermine oxidase (Smox) and polyamine oxidase (Paox). Transcriptomic analyses of mouse and human islets exposed to proinflammatory cytokines revealed induction of Smox/SMOX but no change in Paox/PAOX, suggesting a potential role for Smox in inflammation-associated oxidative stress in islets. In developing zebrafish, the smox gene is expressed in the pancreas and enriched within endocrine cells. Using a β-cell-specific ROS-inducible transgenic zebrafish model, smox knockdown reduced intra-islet ROS and macrophage recruitment. Metabolomic profiling of zebrafish embryos showed that smox deficiency did not affect spermine or spermidine levels but led to the accumulation of acetylated polyamines, consistent with the rerouting of polyamine flux through alternative acetylation pathways to ensure homeostasis of polyamine levels. RNA sequencing of zebrafish embryos demonstrated that smox deficiency induces distinct transcriptional programs, with enrichment of cell cycle and RNA processing pathways at baseline and reprogramming of stress, translational, and immune-associated pathways during injury. Mechanistically, Smox generates both hydrogen peroxide and the reactive aldehyde acrolein, whereas Paox-dependent pathways produce hydrogen peroxide without acrolein. These findings support a model in which Smox amplifies β-cell stress through aldehyde-mediated toxicity and identify polyamine catabolism as a modifiable pathway in the setting of β-cell injury.

overall_design: RNA sequencing profile of on whole Tg(ins:NTR)s950 zebrafish larvae at 3 days post fertilization (dpf) that had been injected with either control MO or smoxMO, and that had either been subjected to a 6 hr MTZ-injury or left untreated

first: Armando

last: Puente

first: Christian

last: Checkcinco

first: Ryan

last: Anderson

first: Raghavendra

last: Mirmira


title: Menin-RelA complex antagonizes cancer cell-intrinsic and tumour microenvironment-induced NF-κB hyperactivation to suppress pancreatic neuroendocrine tumorigenesis

first: Adrian

last: Teo

summary: Pancreatic neuroendocrine tumours (PNETs) are rare neuroendocrine cancers with high mortality rates and an immense unmet medical need. While the genetic and immune landscape of PNETs is defined, the molecular mechanisms linking these factors to tumorigenesis remain poorly understood. Here, we identify NF-κB signaling as a key effector pathway that contributes to PNET tumorigenesis, regulated through both cancer cell extrinsic and intrinsic mechanisms. CellChat analysis identifies M2-like macrophages as the dominant source of NF-κB-activating cytokines, and co-culture of PNET cancer cells with THP-1-derived M2-macrophages significantly enhances RelA phosphorylation and colony-forming capacity in vitro. Concurrently, we uncovered a cancer cell intrinsic safeguard mechanism wherein the tumour suppressor menin physically associates with RelA to suppress PNET growth in vitro and in vivo. Molecular docking identified key residues mediating the menin-RelA interaction and revealed three clinically relevant menin mutants (P320R, R415P, W423R) that destabilize this complex, compromising menin’s ability to restrain PNET growth. Mechanistically, menin and RelA co-bind κB sites on promoters of proliferation-associated NF-κB target genes, including NR4A1, and epigenetically silence their expression through reduced H3K27ac. Crucially, NR4A1 depletion or small-molecule inhibition suppresses PNET growth in vitro and in vivo. Together, our findings reveal a novel menin-RelA-NR4A1 axis that regulates PNET growth and demonstrates how extrinsic and intrinsic factors converge on NF-κB signaling, highlighting potential therapeutic avenues.

overall_design: RNA-seq profiling of pancreatic neuroendocrine tumour tissues  with and without MEN1 mutations

first: Claire Wen Ying

last: Neo

first: Jun Wei

last: Chan

first: Gokce


title: RNA-seq analysis of splenic IgG1 or IgM plasma cells

city: Suita

first: Daisuke

last: Motooka

state: Osaka

address: 3-1, Yamadaoka

institute: NGS core facility, Research Institute for Microbial Diseases, Osaka University

summary: In a typical primary immune response, the BCR is brought about by IgM to IgG isotype switching, wherein B cells switched to IgG give rise to more long-lived plasma cells (LLPCs). How such isotype-driven bias takes place still remains unclear. Here, we showed that IgG1 germinal center (GC) B cells presented higher levels of antigens to Tfh cells, making the resultant plasma cells more proliferate than IgM ones, and that BCR signal through IgM conferred more Bim-dependent apoptosis on their plasma cells, together dominating the numbers of IgG1 over IgM plasma cells in the secondary lymphoid tissues. In addition, IgG1 plasma cells were more prone to migrate to bone marrow than IgM ones. Hence, our findings suggest that differential activities in antigen presentation and signaling through IgG1 type BCRs contribute to enrichment of IgG1 plasma cells in the bone marrow long-lived plasma cell compartment.

overall_design: Congenially marked B1-8germ B cells were transferred into C57BL/6J wild-type hosts, which were immunized with NP-CGG/alum on day0. On day7, donor  splenic  IgG1 or IgM plasma cells were sorted by using FACSAriaII.

first: Yuki

last: Tai

first: Takuya

last: Koike

first: Tomohiro

last: Kurosaki


title: RNA-seq analysis of germinal center-derived splenic IgG1 or IgM plasma cells

overall_design: Congenially marked S1PR2-CreERT2 Ai14 B1-8germ B cells were transferred into wild-type hosts, which were immunized with NP-CGG/alum on day0, treated with tamoxifen on day5, 6. On day10, donor splenic tdTomato+ IgG1 or IgM plasma cells were sorted by using FACSAriaII.


title: Bromodomain Inhibitors to Prevent Development of Resistance to Targeted Kinase Inhibitors in Schwannomas [ChIP-seq]

city: Orlando

first: Cristina

last: Fernandez-Valle

state: FL

address: 6850 Lake Nona Blvd.

institute: Unviersity of Central Florida College of Medicine

summary: Neurofibromatosis type 2 (NF2) is an inherited disorder that promotes tumor growth on nerves throughout the nervous system. NF2 affects around 1 in 33,000 individuals worldwide and is caused by loss of function of the merlin tumor suppressor encoded by the NF2 gene. Tumor control early in life is critical for maintaining quality of life. Currently, treatments available for NF2-associated tumors are surgery and radiation therapy. Off-label use of cancer drugs are being tried, as there are no Food and Drug Administration (FDA)-approved drug therapies for NF2. As a member of the SYNODOS for NF2 consortium, we performed unbiased drug combination screening using schwannoma model cell lines. We identified a BRD4 and a PAK inhibitor that acted in concert to selectively slow growth of a human schwannoma line compared to its merlin-expressing parental line. BRD4 is a member of the BET family of bromodomain containing proteins that bind acetylated lysine in transcription regulatory proteins to alter gene expression. BRD proteins contribute to development of resistance to cancer drugs. Follow-up studies confirmed the drugs’ interaction in multiple mouse and human schwannoma lines. We will extend this research by assessing the ability of BRD4 inhibitors in combination with multiple PAK, PI3K, MEK, and FAK inhibitors, some of which are in NF2 clinical trials (selumetinib, crizotinib, brigatinib, trametinib) to reduce the viability of schwannoma lines. We will measure whether the combinations provide long-lasting inhibition of cell proliferation, induce cell death, and block compensatory escape pathways that often arise when cells are treated with a single kinase inhibitor. We will use an established mouse xenograft model to test the effectiveness of the best performing in vitro drug combination. Mechanisms of action studies will complete the preclinical evaluation of the advanced drug combination in a representative cell line. Our proposed study is timely because the results will indicate whether drug resistance could develop for several of the kinase inhibitors in ongoing NF2 clinical trials. Moreover, the results could indicate whether BRD4 inhibitors could serve as an adjuvant therapy to prevent drug resistance. By assessing the RNAome and methylome of single and dual treated human schwannoma cells, we will uncover the genes and RNAs that undergo BRD4-dependent epigenetic regulation to trigger compensatory pathways. With further validation, these candidate genes and RNAs may serve as biomarkers for treatment response and/or resistance development. Thus, these preclinical studies are at the forefront of addressing questions critical to ongoing efforts to develop a pharmacotherapy for NF2 schwannomas.

overall_design: Chip-sequencing of HS02 cells treated with 0.0125% DMSO or 250nM BMS-986158 for 4h.  Three biological replicates were used for each condition.

first: Christina

first: Haley

last: Hardin


title: Dual response of wheat roots to ABA and nitrate [dataset2]

city: Qingdao

first: Junyi

last: Mu

address: No. 72, Binhai Road, Jimo District, Qingdao City

institute: Shandong Unoversity

summary: For analysis of ABA and nitrogen treated transcriptome, wild-type wheat JW1 at 3 days after germination was removed endosperm and cultured on wheat nutrient culture medium containing 2 mM nitrate for 3 days, and then transferred to a nitrogen-free wheat nutrient culture medium for an additional 2 days. Following this, the wheat seedlings were exposed to wheat nutrient culture medium containing 2 mM KCl or 2 mM KNO3, and/or ABA for 3 hours. The roots of wheat were collected and subjected to total RNA extraction using the TriZol RNA extraction kit (TransGen Biotech).

overall_design: The wheat culture solutions contained either: (1) 0 mM nitrate (0N), (2) 2 mM nitrate (2N), or (3) 5 μM abscisic acid (ABA) supplemented to either 0N (0N+ABA) or 2N (2N+ABA) conditions.


title: Humoral pregnancy analyses reveal strategies for fetal protection and aberrancy in miscarriage [1]

city: Boston

first: Stephen

last: Elledge

state: MA

address: 77 Avenue Louis Pasteur

department: Genetics

institute: Harvard Medical School

summary: The maternal immune system must simultaneously defend against pathogens with 25 tolerance of the antigenically distinct fetus. Despite the central importance of immune modulation during pregnancy, epitope-level analyses of the maternal antibody repertoire remain lacking. Here, we performed high-throughput, multi-isotype longitudinal serology of 119 women from preconception through pregnancy, combining phage display of linear peptides with whole protein-based antigen assays to profile antibody responses to viral and self-antigens. We observed a broad 30 expansion of the maternal IgG repertoire and a relative increase in IgA titers, both tracking with pregnancy progression. These changes may augment transplacental and mucosal immunity in the fetus and newborn, respectively. Notably, pregnancies ending in miscarriage exhibited pronounced IgA titer spikes against both viral and self-antigens unrelated to active infection (sensitivity 14/19, 74%, specificity 95%), indicating an underlying immune perturbation may 35 precede pregnancy loss.

overall_design: We performed high-throughput profiling of the antibody repertoire from participant sera using phage immunoprecipitation sequencing (PhIP-Seq) using a synthetic human virome and a synthetic human peptidome. Sequences coding for antibody-bound peptides displayed on phage were sequenced by an Illumina instrument to generate the included data.

first: Brandon

last: Sie

first: Yumei

last: Leng

first: Nadege

last: Nziza

first: Moriah

last: Mitchell

first: Nicholas

last: Webb

first: Yunjoo

last: Lee

first: Sunni L

last: Mumford

first: Enrique F

last: Schisterman

first: H

middle: B

last: Larman

first: Boris

last: Juelg

first: Galit

last: Alter


title: Humoral pregnancy analyses reveal strategies for fetal protection and aberrancy in miscarriage [3]

first: Sunni

first: Enrique

middle: F


title: Dual response of wheat roots to ABA and nitrate [dataset1]

overall_design: The wheat culture solutions contained either: (1) 0 mM nitrate (0N), (2) 2 mM nitrate (2N) conditions.


title: Humoral pregnancy analyses reveal strategies for fetal protection and aberrancy in miscarriage [2]


title: Bromodomain Inhibitors to Prevent Development of Resistance to Targeted Kinase Inhibitors in Schwannomas [RNA-seq]

first: Cristina

overall_design: RNA-sequencing of HS02 and HS05 cells treated with 0.0125% DMSO, 1µM trametinib, 1µM brigatinib, 250nM BMS-986158, 1µM trametinib + 250nM BMS-986158, and 1µM brigatinib + 250nM BMS-986158 for 36h. Five biological replicates were used for each condition.

first: Christina

first: Anna

last: Nagel


title: Prolonged cold exposure enhances regeneration potential in Arabidopsis [ChIP-Seq]

city: Taipei

first: Fu-Yu

last: Hung

address: Institute of Plant Biology, National Taiwan University

country: Taiwan

institute: NTU, IPB

summary: Prolonged cold exposure over winter impacts plant growth and development but its role beyond flowering regulation remains underexplored. In this study we show that extended cold enhances callus formation and shoot regeneration in Arabidopsis seedlings. This enhancement is mediated by cold-induced AP2/ERF transcription factors C-repeat/DRE-Binding Factor 1 (CBF1), CBF2 and CBF3 which interact with the histone acetyltransferace HISTONE ACETYLTRANSFERASE OF THE GNAT FAMILY 1 (HAG1). The CBFs recruit HAG1 to the loci of key regeneration regulators, such as WUSCHEL-RELATED HOMEOBOX 5 (WOX5), to promote their expression via histone acetylation. Our findings thus uncover an epigenetic mechanism by which prolonged cold primes plants for enhanced regeneration, highlighting how environmental cues influence developmental plasticity in plants.

overall_design: Arabidopsis (Arabidopsis thaliana) plants were germinated on MS medium and grown at 22℃ under short day (8 h light /16 h dark cycle) condition for 14 days. For the prolonged cold treatment, 14-day-old Arabidopsis plants were transferred to 4℃ and grown under short day condition for 6 weeks. The hag1 mutant (SALK_048427, hag1–5) was a previously reported T-DNA insertion mutant (Kornet and Scheres, 2009; Chen et al., 2017). The CRISPER-Cas9 generated cbf1/2/3 triple mutants (cbf1/2/3-97 and cbf1/2/3-93) were also reported previously (Xie et al., 2021). All mutants used in this study were in the Col-0 background.

first: Keiko

last: Sugimoto


title: Humoral pregnancy analyses reveal strategies for fetal protection and aberrancy in miscarriage

first: Stephen

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

overall_design: Refer to individual Series


title: Prolonged cold exposure enhances regeneration potential in Arabidopsis


title: R-loop maintains the deposition of H3K36me3 to prevent invasion of H3K4me3 during SN-oocyte development

city: Guangzhou

first: Ying

middle: liang

last: Sheng

state: Guangdong

address: No. 9 XingDaoHuanBei Road, Guangzhou International Bio Island

institute: Guangzhou National Laboratory


title: Effects of dexamethasone and desisobutyryl ciclesonide on gene expression in liver and lung of neonatal rats

city: Pittsburgh

first: Uma

last: Chandran

address: 5607 Baum Blvd

institute: University of Pittsburgh

summary: Infants born before 30 weeks gestation are at risk of developing bronchopulmonary dysplasia (BPD), a prevalent chronic lung disease of prematurity. Glucocorticoids (GCs) such as dexamethasone (DEX) have been a mainstay of BPD prevention as they reduce lung inflammation and injury. However, their use is encumbered with several adverse effects including hyperglycemia, impaired somatic and brain growth and cerebral palsy. Ciclesonide (CIC), an inhaled GC prodrug approved for the treatment of asthma and allergic rhinitis in children, is converted to the potent glucocorticoid receptor (GR) agonist des-ciclesonide (DES) by enzymes enriched in the airways. We previously reported that subcutaneous (s.c.) delivery of CIC in neonatal rats activated GR transcriptional responses in lung but did not trigger the adverse effects on somatic growth, brain weight or cerebral white matter loss caused by DEX leading us to propose CIC as a potential new pharmacotherapy for BPD. To determine whether limited systemic metabolism of CIC in neonatal rats was solely responsible for its enhanced safety profile, we assessed the transcriptome of total lung and liver tissue of neonatal rats followed s.c. delivery of CIC’s active metabolite DES.

overall_design: Gene expression profiling was performed using bulk RNA-Seq data obtained from lung and liver tissue or neonatal rats obtained 24 hours after the final of 5 daily subcutaneous injections of either vehicle (2.5% Ethanol), 0.1 mg/kg dexamethasone or 1.25 mg/kg desisobutyryl ciclesonide that were initiated at postnatal day 1

first: Donald

last: DeFranco

first: Julian

last: Jaumnotte

first: Jiefei

last: Wang