title: Paternal cardiac injury elicits an inflammatory signal relay to the gonads with intergenerational cardiac effects in vertebrates - snATAC-seq_testes_M dataset

status: Public on Aug 16 2026

city: Bern

first: Nadia

last: Mercader

address: Baltzerstrasse 2

country: Switzerland

institute: University of Bern

type: Genome binding/occupancy profiling by high throughput sequencing

summary: The blood-gonadal barrier protects the germline from parental exposures. A phenomenon known as intergenerational inheritance suggests that, exceptionally, this barrier can be surpassed with consequences for the subsequent generation. Specific diet regimes and early traumatic experiences have been among the chronic stressors shown to be able to lead to intergenerational inheritance in mammals. Less is known about how acute stress can affect the germline.  Cardiac damage leads to several alterations in peripheral organs and overall affects alterations in blood flow, metabolism, and the immune response. Whether cardiac damage can also affect the reproductive system is not known and might offer new insights into the potential inheritance of CVD.  Here, we used the zebrafish and mouse models to explore the intergenerational role of cardiac damage and repair. As early as one week after a cardiac cryolesion, male gonads and gametes activated responses associated with inflammation. In sperm, chromatin accessibility was altered in response to cardiac cryolesion and offspring of cryoinjured zebrafish males, revealing changes in cardiac function and cardiac gene expression. Induction of systemic sterile inflammation in the paternal generation mimicked a cardiac injury effect in the following generation, while anti-inflammatory treatments in the injured paternal generation partially recovered F1 cardiac features. Chromatin accessibility was also altered in mouse testis after a neonatal injury, and F1 hearts revealed alterations in gene expression associated with the immune response, suggesting a conserved role of sterile inflammation as a vector for intergenerational transmission of cardiac injury.  This submission covers the snATAC-seq_testes_M assay.

overall_design: Single-nucleus ATAC-seq was performed on whole testis from adult C57BL/6J mice that underwent neonatal (P1) cardiac cryoinjury (n=3) versus uninjured controls (n=4), to identify cell-type-resolved chromatin accessibility changes in germ cell populations following cardiac injury.

first: Benedetta

last: Coppe

first: Prateek

last: Arora


title: Paternal cardiac injury elicits an inflammatory signal relay to the gonads with intergenerational cardiac effects in vertebrates - Bulk-RNA-seq_F1_heart_M dataset

type: Expression profiling by high throughput sequencing

summary: The blood-gonadal barrier protects the germline from parental exposures. A phenomenon known as intergenerational inheritance suggests that, exceptionally, this barrier can be surpassed with consequences for the subsequent generation. Specific diet regimes and early traumatic experiences have been among the chronic stressors shown to be able to lead to intergenerational inheritance in mammals. Less is known about how acute stress can affect the germline.  Cardiac damage leads to several alterations in peripheral organs and overall affects alterations in blood flow, metabolism, and the immune response. Whether cardiac damage can also affect the reproductive system is not known and might offer new insights into the potential inheritance of CVD.  Here, we used the zebrafish and mouse models to explore the intergenerational role of cardiac damage and repair. As early as one week after a cardiac cryolesion, male gonads and gametes activated responses associated with inflammation. In sperm, chromatin accessibility was altered in response to cardiac cryolesion and offspring of cryoinjured zebrafish males, revealing changes in cardiac function and cardiac gene expression. Induction of systemic sterile inflammation in the paternal generation mimicked a cardiac injury effect in the following generation, while anti-inflammatory treatments in the injured paternal generation partially recovered F1 cardiac features. Chromatin accessibility was also altered in mouse testis after a neonatal injury, and F1 hearts revealed alterations in gene expression associated with the immune response, suggesting a conserved role of sterile inflammation as a vector for intergenerational transmission of cardiac injury.  This submission covers the Bulk-RNA-seq_F1_heart_M assay.

overall_design: Bulk RNA-seq was performed on mouse (uninjured) hearts collected from offspring of males that underwent neonatal (P1) cardiac cryoinjury versus uninjured males. Mice strain: C57BL/6J


title: Extracellular matrix regulates lineage plasticity in prostate cancer through YAP/TEAD

city: New York

first: Teng

last: Han

state: New York

address: 417 E 68th St

country: USA

institute: MSKCC

summary: Treatment-related neuroendocrine prostate cancer (NEPC) is an increasingly frequent mechanism of resistance to androgen receptor pathway inhibitor (ARPI) therapy in prostate adenocarcinoma (PRAD). This lineage transition is dependent on upregulation of the NE-specifying transcription factor ASCL1, typically in a genetic background of RB1 and TP53 loss. Here we identify extracellular matrix-integrin-YAP1/TEAD signaling as a critical brake on NEPC lineage transition. Deletion of Itgb1, the shared B1 subunit required for collagen and laminin-mediated integrin activation, is sufficient to induce ASCL1 and NE lineage gene expression, by activating LATS1/2 kinases with subsequent inactivation of YAP1/TEAD signaling. Conversely, restoration of YAP1/TEAD signaling by pharmacological LATS1/2 inhibition, or by expression of constitutively active YAP1/TAZ mutants, prevents or reverts NEPC lineage transition. NOTCH and AR cooperate with YAP/TEAD to repress ASCL1, such that combined inhibition leads to complete reprograming of PRAD into NEPC in vitro, providing a dynamic platform to dissect the molecular events responsible for lineage transition over time. We find that lineage transition is accompanied by a redistribution of FOXA1 and TEAD cistromes from PRAD to NEPC-specific enhancers and requires the pioneering activity of FOXA1. Thus, extracellular matrix/integrin signaling in the PRAD tumor microenvironment restrains NE lineage plasticity, highlighting a potential path for pharmacological inhibitors in modulating treatment-induced lineage change.

overall_design: Bulk RNA-seq was performed to characterize the molecular mechanisms underlying prostate adenocarcinoma-to-neuroendocrine prostate cancer lineage transition.

first: Han

last: Teng

first: Lange

last: Matthew

first: Cho

last: Y Zoe

first: Mcgillivray

last: Patrick

first: Buttner

last: Maren

first: Koche

last: Richard

first: Sawyers

last: Charles


title: Early Transcriptomic Response of Leptospira interrogans in an Ovine Dialysis Membrane Chamber Model

city: Krakow

first: Tomasz

last: Szmatoła

state: Małopolskie

address: Mickiewicza 21

department: OMEI

country: Poland

institute: University of Agriculture in Krakow

summary: Leptospirosis is a major zoonotic disease affecting both public health and livestock production. In ruminants, serovar Hardjo is of particular importance because of its ability to establish persistent infections, whereas serogroup Icterohaemorrhagiae is generally associated with incidental infection. The molecular basis of adaptation of serovar Hardjo to the ruminant host remain poorly understood. . The dialysis membrane chamber (DMC) model enables investigation of the short-term transcriptional response of leptospires to the host environment, including nutrient limitation, temperature and osmotic shifts, and soluble host-derived factors. In this study, an ovine peritoneal DMC model was used to compare the transcriptional responses of L. interrogans serovar Hardjo strains KR40 and N116 with those of L. interrogans serogroup Icterohaemorrhagiae strains KR93 and KR95. For each strain, transcriptomic data were obtained after 24 h and 72 h of incubation in DMCs, as well as from in vitro cultures grown in T80/40/LH medium. This experimental design enabled the identification of shared and strain-associated transcriptional responses to the host environment.

overall_design: RNA-seq profiling of Leptospira interrogans serovar Hardjo strains KR40 and N116 and serogroup Icterohaemorrhagiae strains KR93 and KR95 cultured in vitro in T80/40/LH medium and incubated in ovine peritoneal DMCs for 24 h and 72 h, with three replicates for each strain and experimental condition.

first: Klaudia

last: Dubniewicz

first: Laura

last: Pardyak

first: Artur

last: Gurgul

first: Igor

last: Jasielczuk

first: Zbigniew

last: Arent


title: Highly compound mutation of mir-51-56 (miR-100) microRNA binding sites is phenotypically silent in C. elegans

city: Bethesda

first: Kasuen

last: Kotagama

state: MD

address: 50 South Dr

department: NIDDK

institute: National Institutes of Health

summary: MicroRNA (miRNA) are small non-coding RNAs that regulate gene expression post-transcriptionally by targeting mRNAs for translational inhibition and degradation. MiRNAs are functionally categorized into families based on nucleotides 2-7 at their 5ʹ ends, known as the “seed” region. Members of a miRNA family are often functionally redundant due to their largely overlapping targets. The mir-51-56/miR-100 family of miRNAs is widely conserved across metazoans, represented by mir-51-56 in C. elegans. The mir-51-56 family is required for embryonic viability, in which the family members function redundantly. To better understand the roles of mir-51-56 in development, we examined mutants in which mir-51-56 dosage is reduced (mir-52; mir-54-56 deletion), allowing bypass of embryonic lethality and characterization of post-embryonic phenotypes. These mutants display developmental delay, reduced brood size, mating defects, and behavior and gene expression changes reflective of caloric restriction. To assess the functional importance of mir-51 family targets in these phenotypes, we queried a list of putative targets using a focused RNAi screen and mRNA-sequencing.  Through these efforts, we narrowed down a candidate list of 31 mir-51 family targets, which we investigated for their potential to recapitulate mir-52; mir-54-56 phenotypes upon derepression. To this end, we used CRISPR to mutate the miRNA binding sites in all 31 putative target genes, generating single mutant strains as well as multiple highly compound mutant strains with up to thirteen genes with mutated miRNA binding sites. Surprisingly, single and highly compound binding site mutants were largely wild type and do not recapitulate phenotypes of mir-52; mir-54-56. These results may suggest that the mir-51-56 family loss of functions phenotypes are driven by the simultaneous derepression of a large number of targets and thus technically challenging to effectively model genetically.

overall_design: RNA-seq profiling of L4 staged C. elegans collected based on distil tip cell migration visualized using a lag-2::GFP reporter. Strains were grown at 25 C and 500 individual worms were picked directly into Trizol for RNA extraction.

first: Acadia

last: Grimme

first: Rima

last: Sakhawala

first: Lecong

last: Zhou

first: Katherine

last: McJunkin


title: Differential bioenergetic reprogramming driven by sorafenib reveals therapeutic vulnerabilities in biliary tract cancers

status: Public on Aug 15 2026

city: Shanghai

first: Yingbin

last: Liu

state: Shanghai

address: Dongfang Road1630

country: China

institute: Department of Biliary-Pancreatic Surgery, Renji Hospital Affiliated to Shanghai Jiao Tong University School of Medicine

summary: Biliary tract cancers (BTCs) comprise biologically heterogeneous subtypes with limited therapeutic options and variable responses to sorafenib. The biological basis underlying this variability remains unclear. In this study, we compared intrahepatic cholangiocarcinoma (iCCA) and gallbladder cancer (GBC) models under defined sorafenib exposure conditions using transcriptomic profiling, Seahorse-based mitochondrial stress assays, pharmacologic combination analysis, and patient-derived organoid models. In representative iCCA models, 1.25 μM sorafenib increased mitochondrial respiration and ATP production, whereas 10 μM sorafenib suppressed this respiratory adaptation. In contrast, representative GBC models exhibited persistent suppression of mitochondrial respiratory function across the tested conditions and did not display a comparable concentration-dependent shift. Integrated transcriptomic and pharmacologic analyses further identified mitochondrial Complex I as a treatment-relevant vulnerability under sorafenib exposure, with stronger combination interactions observed in iCCA models. These findings indicate that iCCA and GBC differ in their metabolic responses to sorafenib and highlight subtype-specific differences in mitochondrial adaptation under treatment stress.

overall_design: The experiment used two human biliary tract cancer cell lines, HuCCT1 and OCUG-1. Each cell line was assigned to four treatment conditions: vehicle control, 1.25 uM sorafenib, 10 uM sorafenib, and 1.25 uM sorafenib plus 1 uM IACS-010759. Cells were collected after 72 h of treatment. Three independent biological replicates were analyzed per cell line and condition, resulting in 24 RNA-seq libraries. Four OCUG-1 biological libraries underwent additional sequencing in separate L2 and L3 runs; the run-specific paired-end FASTQ files were treated as technical sequencing replicates of the same biological library.

first: Wenhua

last: Zhang

first: Beixuan

last: He

first: Lei

first: Zixin

last: Li

first: Meilin

last: Ma

first: Jiaying

last: Xie

first: Xinyu

last: Wang

first: Zhen

last: Fang

first: Zhuying

last: Yue

first: Ziru

last: Xue

first: Ning

last: Tang

first: Jie

first: Ziming

last: Yin

first: Yanjing


title: Paternal cardiac injury elicits an inflammatory signal relay to the gonads with intergenerational cardiac effects in vertebrates - DNA_Met_sperm_M dataset

first: Nadia

last: Mercader

summary: The blood-gonadal barrier protects the germline from parental exposures. A phenomenon known as intergenerational inheritance suggests that, exceptionally, this barrier can be surpassed with consequences for the subsequent generation. Specific diet regimes and early traumatic experiences have been among the chronic stressors shown to be able to lead to intergenerational inheritance in mammals. Less is known about how acute stress can affect the germline.    Cardiac damage leads to several alterations in peripheral organs and overall affects alterations in blood flow, metabolism, and the immune response. Whether cardiac damage can also affect the reproductive system is not known and might offer new insights into the potential inheritance of CVD.    Here, we used the zebrafish and mouse models to explore the intergenerational role of cardiac damage and repair. As early as one week after a cardiac cryolesion, male gonads and gametes activated responses associated with inflammation. In sperm, chromatin accessibility was altered in response to cardiac cryolesion and offspring of cryoinjured zebrafish males, revealing changes in cardiac function and cardiac gene expression. Induction of systemic sterile inflammation in the paternal generation mimicked a cardiac injury effect in the following generation, while anti-inflammatory treatments in the injured paternal generation partially recovered F1 cardiac features. Chromatin accessibility was also altered in mouse testis after a neonatal injury, and F1 hearts revealed alterations in gene expression associated with the immune response, suggesting a conserved role of sterile inflammation as a vector for intergenerational transmission of cardiac injury.    This submission covers the DNA_Met_sperm_M assay: genome-wide DNA methylation profiling of mouse spermatozoa using the Infinium Mouse Methylation BeadChip (Illumina).

overall_design: Sperm DNA methylation was profiled in adult C57BL/6J male mice using the Infinium Mouse Methylation BeadChip. Three uninjured control males (32 wpp) and four cardiac-cryoinjured males (CI, performed at P1; 37 wpp) were compared - 7 samples total, run on one Sentrix BeadChip.

first: Benedetta

last: Coppe

first: Prateek

last: Arora


title: Extracellular matrix regulates lineage plasticity in prostate cancer through YAP/TEAD [Cut & Run]

first: Teng

last: Han

overall_design: CUT and RUN was performed to characterize the molecular mechanisms underlying prostate adenocarcinoma-to-neuroendocrine prostate cancer lineage transition.

first: Han

last: Teng

first: Lange

last: Matthew

first: Cho

last: Y Zoe

first: Mcgillivray

last: Patrick

first: Buttner

last: Maren

first: Koche

last: Richard

first: Sawyers

last: Charles


title: Melatonin improves ovum pick-up efficiency and oocyte quality in dairy cows by modulating follicular steroidogenesis and mitigating oxidative stress

city: Beijing

first: Kui

middle: Wen

last: Ma

address: No.2 Yuanmingyuan West Road, Haidian District

institute: China Agricultural University

summary:
Background Ovum pick-up (OPU) enables repeated, high-frequency oocyte retrieval from elite dairy cow donors, facilitating rapid genetic progress. However, oocytes obtained via OPU and subsequently subjected to in vitro maturation frequently suffer from severe oxidative stress, mitochondrial dysfunction, DNA damage, and incomplete meiotic maturation, resulting in lower pregnancy rates compared to in vivo-derived embryos. While melatonin (MT) benefits bovine oocyte maturation and embryonic development, its specific cellular and molecular mechanisms in enhancing the competence of OPU-retrieved oocytes remain incompletely understood.
Results: This study investigated the effects of MT on the developmental competence of oocytes collected by OPU from Holstein cows, integrating oocyte quality assessment, follicular fluid metabolomics, and blastocyst transcriptomics. Subcutaneous administration of 80 mg/cow MT prior to OPU significantly increased the proportion of high-quality Grade A oocytes (3.40 ± 0.37 vs 1.40 ± 0.27, P < 0.05) and reduced the proportion of Grade D oocytes (2.80 ± 0.42 vs 8.80 ± 1.26, P < 0.05). Mechanistically, MT alleviated systemic oxidative stress, enhanced glutathione metabolism, and prevented premature luteinization by reducing serum progesterone. Untargeted metabolomics further revealed that MT reshaped the follicular fluid microenvironment through the upregulation of estrogen derivatives and glutathione-related pathways. Transcriptomic analysis of ovarian cells showed significant upregulation of the rate-limiting genes steroidogenic acute regulatory protein (STAR) and 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR). In vitro, supplementation with 10^-7 mol/L MT in oocyte maturation media significantly improved cleavage (87.43 ± 1.59 vs 73.19 ±2.77, P < 0.05) and blastocyst rates (46.99 ± 5.67 vs 32.97 ± 2.38, P < 0.05), scavenged intracellular reactive oxygen species (ROS), and increased total blastocyst cell numbers. Smart-seq2 analysis demonstrated that MT reprogrammed the embryonic transcriptome by activating the AMPK, FoxO, and autophagy pathways while inhibiting endoplasmic reticulum stress and cellular senescence.
Conclusions MT effectively optimizes OPU efficiency by dually improving the follicular microenvironment and protecting embryos from oxidative damage. These findings provide the first in vivo evidence of MT's multi-layered action in a repeated OPU model and establish a strong basis for its clinical application in commercial dairy breeding to mitigate the competence-limiting stress of frequent follicular aspiration.

overall_design: Blastocysts from the MT-treated (n = 3) and control (n = 3) groups were frozen in liquid nitrogen and stored at -80 °C until RNA isolation and sequencing.

first: Wenkui

first: Guoshi

last: Liu


title: Targeted O-GlcNAcylation Enables Functional Rewiring of c-Myc

city: Hong Kong

first: Tongyang

last: Xu

address: 8/F, Area 39, CUHK

department: School of Pharmacy

country: Hong Kong

institute: The Chinese University of Hong Kong

summary: c-Myc is a transcription factor that drives tumorigenesis in many cancers. It is notoriously difficult to directly target c-Myc, mainly due to its lack of well-defined druggable pockets. O-linked β-N-acetylglucosamine modification (O-GlcNAcylation) is a post-translational modification (PTM) playing an important role in regulating c-Myc functions in cancer, while traditionally the studying methods perturbates global O-GlcNAcylation. Here, we report a bifunctional O-GlcNAcylation TArgeting Chimera (OGTAC) molecule, which can induce the proximity of c-Myc and a fusion O-GlcNAc transferase (OGT) in living cells, and thereby enhancing the O-GlcNAcylation of c-Myc. The c-Myc-targeting OGTAC exhibits anti-proliferation effect on cancer cell line. Transcriptomic profiling indicates that OGTAC rewires c-Myc transcriptional activity and reprograms expression of the downstream oncogene MALAT1, in an O-GlcNAcylation-dependent manner. Overall, OGTAC presents a novel chemically induced proximity (CIP)-based tool to target and rewire c-Myc activity in cancer.

overall_design: Cut&Tag-seq of c-Myc in HEK293T-fOGT stable cell line with Flag-c-Myc overexpression. Treatment condition: CBD (1 μg/mL named "A") or OGTAC (1 μg/mL named "B") for 24 h.

first: Billy Wai-Lung

last: Ng


title: Multi-tissue gene expression in HNSCC

city: Ljubljana

first: Emanuela

last: Boštjančič

address: Korytkova 2, Ljubljana

country: Slovenia

institute: University of Ljubljana, Faculty of Medicine, Institute of Pathology

summary: The molecular mechanisms in the development of laryngeal and hypopharyngeal squamous cell carcinoma (LHSCC) remain poorly understood. Previous studies suggest molecular overlap between head and neck SCC (HNSCC) and lung SCC. In this study, we investigated whether lung cancer-associated genes are enriched among differentially expressed genes during stepwise LHSCC development. Spatial transcriptomic profiling using the Xenium platform (10x Genomics) was performed on formalin-fixed paraffin embedded tissue of normal mucosa, low-grade dysplasia (LG-Dys), high-grade dysplasia/carcinoma in situ (HG-Dys/CIS) and invasive carcinoma from eleven patients. Over 40 differentially expressed genes were identified, grouped into key biological processes, including transport, immune modulation, epithelial integrity, signaling and metabolism. Gene expression patterns segregated lesions into two molecular groups, whereby LG-Dys resembled normal mucosa, while HG-Dys aligned with CIS. Six genes (CCDC39, DNAAF1, GDF15, GKN2, RGS16 and TSPAN19) were consistently altered between HG-Dys/CIS and invasive carcinoma, highlighting them as potential biomarkers of malignant transformation. Additionally, EPCAM and SERPINB3 showed altered expression in LHSCC development, consistent with previous studies in other epithelial malignancies. These findings further support similar genetic pathways involved in lung cancer and LHSCC development. Furthermore, our results revealed novel molecular events underlying LHSCC development and identified candidate biomarkers of early invasiveness.

overall_design: Comparisson of normal mucosa/low-grade dysplasia to high-grade dysplasia/carcinoma in situ; normal mucosa/low-grade dysplasia to SCC; high-grade dysplasia/carcinoma in situ to SCC: to identify similarity expression of lung-associated genes between development of head and neck SCC and lung carcinoma.


title: Paternal cardiac injury elicits an inflammatory signal relay to the gonads with intergenerational cardiac effects in vertebrates - Bulk_RNA-seq_testes_ZF dataset

first: Nadia

summary: The blood-gonadal barrier protects the germline from parental exposures. A phenomenon known as intergenerational inheritance suggests that, exceptionally, this barrier can be surpassed with consequences for the subsequent generation. Specific diet regimes and early traumatic experiences have been among the chronic stressors shown to be able to lead to intergenerational inheritance in mammals. Less is known about how acute stress can affect the germline.  Cardiac damage leads to several alterations in peripheral organs and overall affects alterations in blood flow, metabolism, and the immune response. Whether cardiac damage can also affect the reproductive system is not known and might offer new insights into the potential inheritance of CVD.  Here, we used the zebrafish and mouse models to explore the intergenerational role of cardiac damage and repair. As early as one week after a cardiac cryolesion, male gonads and gametes activated responses associated with inflammation. In sperm, chromatin accessibility was altered in response to cardiac cryolesion and offspring of cryoinjured zebrafish males, revealing changes in cardiac function and cardiac gene expression. Induction of systemic sterile inflammation in the paternal generation mimicked a cardiac injury effect in the following generation, while anti-inflammatory treatments in the injured paternal generation partially recovered F1 cardiac features. Chromatin accessibility was also altered in mouse testis after a neonatal injury, and F1 hearts revealed alterations in gene expression associated with the immune response, suggesting a conserved role of sterile inflammation as a vector for intergenerational transmission of cardiac injury.  This submission covers the Bulk_RNA-seq_testes_ZF assay.

overall_design: Bulk poly(A) RNA-seq was performed on testes from wild-type zebrafish males, either uninjured or at 1, 7, or 130 days after cardiac cryoinjury (dpi), to characterize the time course of gene expression changes in the gonad following cardiac damage.


title: snRNAseq of intact and wounded atlantic spiny dogfish sharks (Squalus acanthias)

city: Stockholm

first: Jakob

last: Wikstrom

address: K2 Medicin, Solna, K2 Derm o Ven

department: Dermatology and Venereology

country: Sweden

institute: Karolinska Institutet

summary: We have employed a single nuclei RNAseq approach using 10x Genomics snRNAseq to study cell population dynamics during skin wound healing in spiny dogfish sharks.

overall_design: Intact and wounded skin was harvested using punch biopsy tools and immediately frozen.

first: Etty

last: Bachar-Wikstrom

first: Anthony

last: Anselmo

first: Aaron

middle: R

last: Thorner

first: Inga

last: Sidor

first: Lisa

last: Abbo

middle: D


title: Establishing AAV.PRPF31 gene augmentation in PRPF31-deficient RPE and photoreceptor cells and assessing its efficacy in restoring RPE and photoreceptor function

city: Leeds

first: LeedsOmics

last: UoLeeds

state: West Yorkshire

address: Clarendon Way

department: Cross-faculty

country: United Kingdom

institute: University of Leeds

summary:
Purpose
Retinitis pigmentosa (RP) is a group of inherited retinal disorders characterised by progressive degeneration of the mid-peripheral retina, leading to night blindness and eventual loss of visual acuity. RP11, caused by mutations in the pre-mRNA processing factor 31 (PRPF31) gene, involved in pre-mRNA splicing as a key component of the spliceosome, accounts for approximately 10% of autosomal dominant RP (adRP) cases. Previous studies have shown that PRPF31 mutations disrupt pre-mRNA splicing of other splicing-related genes, resulting in global spliceosome dysregulation, reduced spliceosome activity, leading to accumulation of insoluble cytoplasmic aggregates, cell dysfunction and ultimately retinal cell death.
The pathogenic mechanism is consistent with haploinsufficiency, as the mutant PRPF31 is excluded from the active spliceosome and resulting levels of the gene are insufficient. Therefore, PRPF31 gene augmentation via adeno-associated virus (AAV) makes a promising therapeutic strategy. This study aims to assess the efficiency of PRPF31.AAV gene therapy in restoring PRPF31 expression and function in RPE and photoreceptors, focusing on restoring spliceosome dysregulation, reduction of cytoplasmic aggregates and rescuing cellular phenotypes.
Approach
Using induced pluripotent stem cells (iPSC) derived from patients with severe RP11, we generated retinal organoids and RPE cells models. Both photoreceptors and RPE cells were treated with ShH10.CMV.PRPF31.AAV to enhance PRPF31 expression. The therapeutic impact of PRPF31.AAV was assessed through qPCR and immunoblotting for gene and protein expression of PRPF31 and immunofluorescence analysis of splicing markers, cilia and cytoplasmic aggregates. Lastly, the phagocytotic function of AAV-treated RPE cells was assessed using fluorescently labelled photoreceptor outer segments (POS).
Results
PRPF31.AAV treatment resulted in a nearly two-fold increase of total PRPF31 expression in RPE cells and a ten-fold increase in photoreceptors, compared to GFP.AAV controls, as assessed by qPCR. Quantification of protein levels confirmed a significant elevated PRPF31 levels in PRPF31.AAV treated photoreceptors.
Moreover, PRPF31 localisation was corrected, and nuclear splicing speckles were increased, indicative of restored nuclear speckle morphology and splicing functions in RPE cells. A significant reduction in cytoplasmic aggregates of degradation-related protein HSPB1 and retinal-specific protein RLBP1 was observed in AAV treated RP11-RPE cells and photoreceptors, when compared to controls. A significant increase in both cilia length and incidence was observed in RPE cells upon AAV augmentation. Finally, the phagocytic capacity of RPE cells was restored following PRPF31.AAV treatment, indicating restoration of RPE function.
Conclusions
Our findings demonstrate that PRPF31.AAV gene augmentation therapy effectively restores critical functions in both RPE and photoreceptors. This highlights the therapeutic potential of an AAV-based gene therapy for patients with PRPF31-related adRP.

overall_design: RNA-seq of patient RP11 iPSC-derived RPE cells and organoids either treated with GFP.AAV (control) or PRPF31.AAV

first: Maria

last: Elia

first: Valda

last: Pauzuolyte

last: Georgiou

first: Sina

last: Mozaffari-Jovin

first: Sushma

last: Grellscheid

first: Elton

last: Vasconcelos

first: Colin

last: Johnson

first: Gerrit

last: Hilgen

first: Alexander

last: Smith

first: Robin

last: Ali

first: Majlinda

last: Lako


title: Single-Cell RNA Sequencing Analysis of Mouse Corneal Transplantation Models Under Tacrolimus and Rapamycin Treatment

city: Changsha

first: Limin

last: Xie

state: Hunan

address: No.139，Renmin Road Central Changsha, Hunan, China

institute: The second xiangya hospital of central south university

summary: In this study, we utilized single-cell RNA sequencing (scRNA-seq) to investigate the effects of tacrolimus and rapamycin on corneal graft survival following penetrating keratoplasty in mice. Post-transplantation, the recipient mice were administered daily intraperitoneal injections of tacrolimus, rapamycin, or PBS. Fifteen days after treatment, scRNA-seq was employed to detect molecular and cellular changes within the corneal tissues.

overall_design: Corneal transplants from C57BL/6 to BALB/c mice (allogeneic) and from BALB/c to BALB/c (isogeneic). The allogeneic recipient mice were divided into three treatment groups: tacrolimus, rapamycin, and PBS (control). Post-transplantation, scRNA-seq was performed on corneal tissues to evaluate gene expression changes.

first: Yan

last: He

first: Tuo

last: Deng

first: Yating

last: Liu

first: Yingyi

first: Xixuan

last: Huang

first: Huanmin

last: Kang


title: Transcriptomic Characterisation of Mouse Embryonic Stem Cell-Derived Hepatocyte-Like Cells Generated Using an Advanced Hepatic-Inducing Cocktail (A-HIC)

city: Edinburgh

first: Sari

last: Pennings

state: Scotland

address: 47 Little France Crescent

department: Institute for Neuroscience and Cardiovascular Research

institute: University of Edinburgh

summary: Reliable generation of hepatocyte-like cells (HLCs) from pluripotent stem cells remains limited by cellular heterogeneity and incomplete maturation. In this study, we evaluated an advanced hepatic-inducing cocktail (A-HIC) for the differentiation of E14TG2a mouse embryonic stem cells (mESCs) into HLCs, combining molecular and functional characterisation with bulk RNA sequencing to assess their hepatic phenotype and developmental maturity.  A-HIC-derived HLCs exhibited hepatic morphological and molecular characteristics and demonstrated functional competence through glycogen storage, inducible urea production, glutathione synthesis and depletion, active indocyanine green (ICG) uptake and clearance, and cytochrome P450 inducibility. Flow cytometry further demonstrated a high proportion of ASGR1-positive cells, supporting acquisition of a more mature hepatocyte-like phenotype.  Bulk RNA sequencing was performed on four independently generated A-HIC-derived HLC samples. Transcriptomic profiles were benchmarked against publicly available hepatic reference datasets to assess their relationship to mouse hepatocyte development and to the AML12 mouse hepatocyte cell line. Weighted gene co-expression network analysis (WGCNA) was used to identify co-expression modules and compare module-level expression patterns with purified mouse hepatocytes representing developmental stages E11.5, E15.5, P1, P10, P30 and week 8. Developmental-stage associations were further evaluated using Spearman correlation analysis and hepatic marker gene expression.  A-HIC-derived HLCs displayed transcriptomic characteristics spanning foetal-to-postnatal hepatocyte development, with the strongest overall correspondence extending from late foetal to early postnatal stages. Of the genes analysed in the developmental comparison, 75.3% of A-HIC genes could be associated with a developmental stage, compared with 45.0% for AML12 cells. Developmental-stage mapping and hepatic marker expression therefore indicated broader and more advanced developmental alignment of A-HIC-derived HLCs than AML12 cells.  Together, the functional and transcriptomic analyses support the hepatic identity and functional maturation of A-HIC-derived HLCs. These RNA-seq data provide a resource for characterising mESC-derived hepatocyte-like cells and assessing their developmental maturity relative to established mouse hepatic reference models.

overall_design: Four independent biological replicates of mouse embryonic stem cells (mESCs, E14TG2a) were differentiated into hepatocyte-like cells (HLCs) using the advanced hepatic-inducing cocktail (A-HIC) differentiation protocol. Each replicate represented an independently generated A-HIC differentiation culture. Total RNA was isolated from the resulting A-HIC-derived HLCs and subjected to bulk mRNA sequencing to characterise their transcriptomic profile and assess hepatic identity and developmental maturity. Transcriptomic profiles were subsequently compared with publicly available reference datasets comprising purified mouse hepatocytes across developmental stages (E11.5, E15.5, P1, P10, P30 and week 8) and the AML12 mouse hepatocyte cell line. Weighted gene co-expression network analysis (WGCNA) and developmental-stage correlation analyses were used to evaluate the relationship between A-HIC-derived HLCs and reference hepatic models. Only the four independently generated A-HIC-derived HLC RNA-seq samples are included in this GEO submission; reference datasets used for comparative analyses were obtained from previously published GEO studies.

first: Beatrice

last: Villani

first: Wenduo

last: Qi


title: Paternal cardiac injury elicits an inflammatory signal relay to the gonads with intergenerational cardiac effects in vertebrates - ATAC-seq_sperm_ZF dataset

first: Nadia

last: Mercader

summary: The blood-gonadal barrier protects the germline from parental exposures. A phenomenon known as intergenerational inheritance suggests that, exceptionally, this barrier can be surpassed with consequences for the subsequent generation. Specific diet regimes and early traumatic experiences have been among the chronic stressors shown to be able to lead to intergenerational inheritance in mammals. Less is known about how acute stress can affect the germline.  Cardiac damage leads to several alterations in peripheral organs and overall affects alterations in blood flow, metabolism, and the immune response. Whether cardiac damage can also affect the reproductive system is not known and might offer new insights into the potential inheritance of CVD.  Here, we used the zebrafish and mouse models to explore the intergenerational role of cardiac damage and repair. As early as one week after a cardiac cryolesion, male gonads and gametes activated responses associated with inflammation. In sperm, chromatin accessibility was altered in response to cardiac cryolesion and offspring of cryoinjured zebrafish males, revealing changes in cardiac function and cardiac gene expression. Induction of systemic sterile inflammation in the paternal generation mimicked a cardiac injury effect in the following generation, while anti-inflammatory treatments in the injured paternal generation partially recovered F1 cardiac features. Chromatin accessibility was also altered in mouse testis after a neonatal injury, and F1 hearts revealed alterations in gene expression associated with the immune response, suggesting a conserved role of sterile inflammation as a vector for intergenerational transmission of cardiac injury.  This submission covers the ATAC-seq_sperm_ZF assay.

overall_design: Chromatin accessibility (ATAC-seq) was profiled in spermatozoa collected from uninjured zebrafish males and from males 7 days after cardiac cryoinjury (dpi).

first: Benedetta

last: Coppe

first: Prateek

last: Arora


title: High-altitude hypoxia suppresses triple-negative breast cancer growth by regulating ferroptosis via PHD2

city: Lanzhou

first: Jianming

last: Tang

state: Gansu

address: No. 1 Donggang West Road, Chengguan District

department: Department of Radiation Oncology

institute: The First Clinical Medical College of Lanzhou University

summary: High-altitude hypoxia may alter triple-negative breast cancer progression, but the underlying mechanisms remain incompletely understood. This study profiled transcriptomic changes in subcutaneous 4T1 tumors from female BALB/c mice maintained under ambient-altitude conditions in Lanzhou (approximately 1,500 m) or in a hypobaric chamber simulating an altitude of 3,500 m and treated with vehicle or the prolyl hydroxylase inhibitor IOX2. RNA sequencing data from 12 tumors were analyzed to identify changes associated with altitude exposure and PHD inhibition. Differential expression and Kyoto Encyclopedia of Genes and Genomes analyses indicated ferroptosis-related transcriptomic alterations, supporting further evaluation of the SLC7A11-GSH-GPX4/ACSL4 axis.

overall_design: Bulk RNA sequencing was performed on 12 subcutaneous 4T1 tumor samples, comprising three biological replicates in each of four groups: MC (ambient altitude at approximately 1,500 m plus vehicle), MI (ambient altitude plus IOX2), HC (hypobaric chamber simulating 3,500 m plus vehicle), and HI (simulated 3,500 m plus IOX2). One independent tumor from a different female BALB/c mouse was used for each library.

first: Shujun

last: Guo

first: Min

last: Gao

first: Ying

last: Zhao

first: Xiaohan

first: Zehui

first: Wanjia

last: Qiao

first: Dan

last: Luo

first: Lingfang

last: Zhang


title: Extracellular matrix regulates lineage plasticity in prostate cancer through YAP/TEAD [ATAC-Seq]

first: Teng

last: Han

overall_design: bulk ATAC-seq was performed to characterize the molecular mechanisms underlying prostate adenocarcinoma-to-neuroendocrine prostate cancer lineage transition.

first: Han

last: Teng

first: Lange

last: Matthew

first: Cho

last: Y Zoe

first: Mcgillivray

last: Patrick

first: Buttner

last: Maren

first: Koche

last: Richard

first: Sawyers

last: Charles


title: Extracellular matrix regulates lineage plasticity in prostate cancer through YAP/TEAD [scMultiome]

overall_design: scMultiome was performed to characterize the molecular mechanisms underlying prostate adenocarcinoma-to-neuroendocrine prostate cancer lineage transition.


title: Single-Cell and Spatial Multi-Omics Reveal Estrogen-Mediated Vaginal Wall Microenvironment Remodeling and a Perivascular Reparative Niche in Postmenopausal Pelvic Organ Prolapse

city: Taiyuan

first: Xiaochun

last: Liu

state: Shanxi

address: No.99 Longcheng Street, Xiaodian district

department: department of gynecology and obstetrics

institute: Shanxi Bethune Hospital

summary: Local estrogen is widely used to improve vaginal mucosal status and menopausal urogenital symptoms in pelvic organ prolapse despite variable clinical outcomes, highlighting a critical gap in our understanding of its actions within the native tissue architecture. To resolve this, we employed high-definition spatial transcriptomics, achieving a near-cellular resolution map of the postmenopausal vaginal wall. This spatial atlas reveals spatial patterns underlying estrogen’s action, the spatial organization of a structured HAS1+ fibroblast-pericyte cellular unit around vasculature. Estrogen is associated with the recruitment of TWIST1-related HAS1+ fibroblasts into this precise micro-anatomical location, enabling their functional coupling with pericytes. This co-localization facilitates a rewired fibroblast-pericyte signaling axis, enhancing intercellular communication. Computational pharmacology further suggests this unit as a potential druggable functional module. Our findings support a model in which estrogen’s effects involve spatially organized formation of a multicellular regulatory unit rather than general tissue stimulation. TWIST1, HAS1, and ECM remodeling are linked within this regulatory program, which may inform future tissue-modulating and symptom-directed strategies.

overall_design: Single-cell RNA-seq and spatial transcriptomics were performed on anterior vaginal wall biopsies from postmenopausal women with uterine prolapse. Untreated control group (n=5: POP-1, POP-5, POP-6, POP-7, POP-8) and topical vaginal estrogen-treated group (n=6: E2-3, E2-4, E2-5, E2-6, E2-7, E2-8). For scRNA-seq: 10x Genomics platform; for spatial transcriptomics: 10x Visium platform.


title: MCART1 (SLC25A51) deficiency exacerbates mitochondrial dysfunction during MPP+-induced complex I stress

first: shiliang

last: wang

address: Dongan Road No.130

institute: Fudan university

summary: Mitochondrial NAD+ homeostasis, sustained by the inner membrane transporter MCART1, is critical for oxidative metabolism and stress resilience. Inhibition of complex I by 1-methyl-4-phenylpyridinium (MPP+) triggers metabolic collapse and mitochondrial dysfunction, yet whether MCART1 provides a protective gatekeeping function against the MPP+ toxin remains unclear. Here, we show that loss of MCART1 exacerbates mitochondrial dysfunction under physiological conditions, and that MCART1 contributes to maintaining membrane potential, preventing ATP depletion, and suppressing ROS accumulation in MPP+-treated neuronal cells. We identify key NAD+-binding residues within the predicted substrate-binding pocket. Mutation of these residues uncouples MPP+ resistance from constitutive NAD+ transport, defining a structural determinant required for the stress-responsive gatekeeping function of MCART1. These findings establish that MCART1 acts as a conditionally indispensable protector of mitochondrial integrity during complex I poisoning, and reveal that failure of this NAD+ influx pathway drives metabolic collapse in the MPP+ toxin model relevant to Parkinson's disease.

overall_design: RNA-seq profiling of SH-SY5Y cells, including MCART1-knockdown cells (shMCART1) and scramble controls (shScramble), MCART1-overexpression cells (oeMCART1) and controls (oeNC). Cells were treated with or without 0.5mM 1-methyl-4-phenylpyridinium (MPP+) for 24 hours.

first: Shiliang

last: Wang

first: Peixin

last: Sun

first: Yue

first: Jinlun Kylian

first: Xurui

last: Shen

first: Hanting

last: Yang


title: Hepatocyte MLKL Drives Obesity-Driven Hepatocellular Carcinoma Progression via Mitochondrial Dysfunction Independent of Necroptosis in MASLD

city: Oklahoma City

first: Jonathan

last: Wren

state: OK

address: 825 N.E. 13th Street

department: Genes & Human Disease Research Program

institute: OMRF

summary: Metabolic dysfunction-associated steatotic liver disease (MASLD) is a leading cause of hepatocellular carcinoma (HCC), particularly in obesity, yet mechanisms linking hepatocyte dysfunction to tumorigenesis remain unclear. Mixed lineage kinase domain-like protein (MLKL), the effector of necroptosis, is elevated in MASLD, but its hepatocyte-intrinsic role in obesity-driven MASLD-HCC is unknown.  Using a long-term Western diet (WD)-induced MASLD-HCC model in hepatocyte-specific MLKL knockout (MlklHepKO) mice, we defined MLKL’s hepatocyte-intrinsic function. WD increased hepatocyte MLKL protein expression without detectable necroptosis activation, indicating a necroptosis-independent role. MLKL deficiency did not alter WD-induced inflammation, fibrosis, or liver injury but increased hepatic lipid accumulation while reducing lipotoxic lipid species and preserving mitochondrial function. WD-fed MlklHepKO mice developed fewer and smaller tumors with reduced incidence, multiplicity, proliferation, and stemness. Transcriptomic analysis revealed upregulation of mitochondrial oxidative phosphorylation pathways in MlklHepKO livers. WD suppressed the mitochondrial fusion protein and tumor suppressor MFN2, whereas MLKL deficiency restored MFN2 expression post-translationally. In HCC cells, MLKL deletion reduced proliferation, improved mitochondrial respiration, and decreased glycolysis; these effects were reversed by MFN2 deletion. MLKL localized to nuclear and mitochondrial compartments, consistent with organelle-intrinsic functions. The human MLKL inhibitor necrosulfonamide (NSA) suppressed HepG2 xenograft growth, and elevated MLKL expression in human HCC correlated with poorer overall survival. Hepatocyte MLKL promotes MASLD-associated HCC through a non-canonical, RIPK3-independent mechanism involving MFN2 suppression, impaired mitochondrial function, and increased tumor proliferation and stemness. These findings identify MLKL as a potential therapeutic target in MASLD-associated HCC.

sample_organism:
Homo sapiens
Mus musculus

platform_organism:
Homo sapiens
Mus musculus

overall_design: For studying the effect of MLKL-dependent effects on HCC cell proliferation and related pathways, MLKL was knocked down in HepG2 cells by siRNA mediated transfection for 48h.

first: Phoebe

last: Ohene-Marfo

first: Sabira

last: Mohammed

first: Chao

last: Jiang

first: Shylesh

last: Bhaskaran

first: Kara

last: Kneuper

first: Satoshi

last: Matsuzaki

first: Bo

last: Hagy

first: Randal

middle: J

last: May

first: Constantin

last: Georgescu

first: Megan

last: John

first: Julianne

middle: N

last: Hoang

first: Kevin

last: Pham

first: Albert

last: Tran

first: Chinthalapally

middle: V

last: Rao

first: Tae Gyu

last: Oh

first: Michael

last: Kinter

first: Willard

middle: M

last: Freeman

first: Courtney

last: Houchen

first: Surendra

last: Shukla

first: Kenneth

last: Humphries

first: Sathyaseelan

middle: S

last: Deepa


title: Paternal cardiac injury elicits an inflammatory signal relay to the gonads with intergenerational cardiac effects in vertebrates - Bulk_RNA-seq_F1_heart_ZF dataset

first: Nadia

last: Mercader

summary: The blood-gonadal barrier protects the germline from parental exposures. A phenomenon known as intergenerational inheritance suggests that, exceptionally, this barrier can be surpassed with consequences for the subsequent generation. Specific diet regimes and early traumatic experiences have been among the chronic stressors shown to be able to lead to intergenerational inheritance in mammals. Less is known about how acute stress can affect the germline.  Cardiac damage leads to several alterations in peripheral organs and overall affects alterations in blood flow, metabolism, and the immune response. Whether cardiac damage can also affect the reproductive system is not known and might offer new insights into the potential inheritance of CVD.  Here, we used the zebrafish and mouse models to explore the intergenerational role of cardiac damage and repair. As early as one week after a cardiac cryolesion, male gonads and gametes activated responses associated with inflammation. In sperm, chromatin accessibility was altered in response to cardiac cryolesion and offspring of cryoinjured zebrafish males, revealing changes in cardiac function and cardiac gene expression. Induction of systemic sterile inflammation in the paternal generation mimicked a cardiac injury effect in the following generation, while anti-inflammatory treatments in the injured paternal generation partially recovered F1 cardiac features. Chromatin accessibility was also altered in mouse testis after a neonatal injury, and F1 hearts revealed alterations in gene expression associated with the immune response, suggesting a conserved role of sterile inflammation as a vector for intergenerational transmission of cardiac injury.  This submission covers the Bulk_RNA-seq_F1_heart_ZF assay.

overall_design: Bulk RNA-seq was performed on ventricles from adult F1 zebrafish, offspring of uninjured and cardiac-cryoinjured (7 dpi) fathers crossed with uninjured females, to assess paternal-injury-associated alterations in offspring cardiac gene expression under homeostatic conditions.

first: Benedetta

last: Coppe

first: Prateek

last: Arora


title: Mechanical injury-induced rat model of esophageal stricture reveals inflammation-associated fibrotic remodeling

city: Heifei

first: Wenyong

last: Wu

state: Anhui

address: No. 632 Furong Road

institute: Anhui Institute of Medicine

summary: Esophageal stricture is an important complication after endoscopic submucosal dissection, but its inflammatory and fibrotic mechanisms remain incompletely understood. A controllable post-ESD-like rat model was established using a customized 3D-printed mechanical injury device. Bulk RNA sequencing of esophageal tissues collected 28 days after injury identified 892 differentially expressed genes between untreated control and mechanically injured rats, including 577 upregulated and 315 downregulated genes. Functional enrichment indicated inflammatory responses, cytokine signaling, extracellular matrix organization, wound healing, TNF signaling, IL-17 signaling, focal adhesion and ECM-receptor interaction. These data characterize inflammation-associated fibrotic remodeling in mechanical injury-induced esophageal stricture.

overall_design: Bulk RNA sequencing was performed on full-thickness esophageal tissues from male Sprague-Dawley rats 28 days after mechanical injury. The study included two groups: untreated controls and rats subjected to localized esophageal mechanical injury using a customized 3D-printed device. Three independent animals were analyzed per group, with one sequencing library generated from each animal. Poly(A)-selected RNA libraries were sequenced as 2 x 150-bp paired-end reads on an Illumina platform.

first: Xueshi

first: Peilin

last: Liu

first: Kai

last: Guo

first: Zichuan

last: Cao

first: Jinlong

last: Hu


title: Genome-wide mapping of NsrC-associated DNA regions in Synechococcus elongatus PCC 7942 by ChIP-seq

city: Jinan

first: Guoyan

last: Zhao

state: Shandon

address: ShanDong Normal University

institute: ShanDong Normal University

summary: This study investigates the genome-wide DNA-binding profile of the small regulatory protein NsrC in Synechococcus elongatus PCC 7942. Chromatin immunoprecipitation sequencing was performed using a strain expressing NsrC fused to mNeonGreen and FLAG (D1339). Two biological ChIP replicates and their matched input controls were analyzed to identify NsrC-associated genomic regions and support evaluation of its role in regulating phycobilisome biosynthesis genes.

sample_organism: Synechococcus elongatus PCC 7942 = FACHB-805

overall_design: Four paired-end ChIP-seq libraries were analyzed: two independent anti-FLAG chromatin-immunoprecipitated DNA samples from the NsrC-mNG-FLAG strain D1339 and two matched non-immunoprecipitated input DNA controls. Each biological replicate consists of one ChIP library and its corresponding input library.

first: Li

last: Wenzhe

first: Liu

last: Qian

first: Fan

last: Shoujin

first: Chen

last: Zhuo

first: Zhang

last: Jian

first: Zhao

last: Guoyan


title: Profiling the novel impacts of the organochlorine compounds tris(4-chlorophenyl) methane (TCPM) and tris(4-chlorophenyl) methanol (TCPMOH) on human placental cells

city: San Diego

first: Elana

last: Elkin

state: CA

address: 5500 Campanile Drive

department: School of Public Health

institute: San Diego State University

summary: Tris(4-chlorophenyl)methane (TCPM) and tris(4-chlorophenyl)methanol (TCPMOH) are anthropogenic environmental pollutants that are believed to be byproducts of the organochlorine pesticide dichlorodiphenyltrichloroethane (DDT). TCPMOH is thought to be a metabolite of TCPM. These chemicals persist in the environment, and have been found to accumulate in aquatic mammal tissue and in human breast milk. They are also potential endocrine disruptors, yet no studies evaluating potential toxic effects have been conducted in the placenta, a transient organ with many endocrine functions critical for fetal development. In this study, TCPM and TCPMOH were screened for its cytotoxic effects, differential gene expression, invasion capacity, and changes to cell cycling. For cell viability and cytotoxicity, HTR-8/SVneo cells were treated with medium plus DMSO (control) or TCPM or TCPMOH (1 µM – 100 µM) for 24-hours and cytotoxicity was measured using Multiplex Multitox Cytotoxicity Assay. RNA sequencing of HTR-8/SVneo cells was used for differential gene expression after being treated with medium plus DMSO (control) or TCPMOH (1 µM or 10 µM). Differential gene expression was analyzed using DEseq2 in R.

overall_design: Differential gene expression in HTR-8/SVneo cells  treated with DMSO vehicle control, 1 μM or 10 μM TCPMOH for 24 hours was explored.

first: Elama

first: Gabriel

last: Romo


title: Rg1 improves motor recovery after spinal cord injury by suppressing astrocytic NLRP2 inflammasome via the TLR4–MyD88–NF-κB pathway

city: suzhou

first: wenjun

last: zou

address: No. 1055, Sanxiang Road, Gu Suzhou District, Suzhou City, Jiangsu Province

institute: The Second Affiliated Hospital of Soochow University

summary: Spinal cord injury (SCI)-induced neuroinflammation and astrocyte pyroptosis severely impede motor functional recovery. Here, we report that ginsenoside Rg1 attenuates astrocyte pyroptosis by regulating the TLR4‑MyD88‑NF‑κB signaling axis, thereby promoting functional recovery in SCI rats. RNA‑seq combined with RT‑qPCR analysis revealed that Rg1 treatment significantly downregulated the transcriptional levels of Tlr4, Myd88, and Map3k7 in primary astrocytes, and reduced the expression and nuclear translocation of downstream NF‑κB pathway phosphoproteins (p‑IKKβ, p‑p65). Collectively, our data provide a molecular framework for the neuroprotective effects of Rg1 after SCI: Rg1 inhibits TLR4‑MyD88‑IKKβ/NF‑κB signaling, downregulates NLRP2 inflammasome‑mediated astrocyte pyroptosis, thereby alleviating neuroinflammation and promoting motor functional recovery. Importantly, the RNA‑seq analysis offers global molecular evidence identifying the key transcriptional pathway (TLR4/MyD88/NF‑κB) targeted by Rg1.

overall_design: RNA‑seq analysis of primary astrocytes from control, SCI (LPS 1 μg/mL, 6–8 h), and Rg1 (80 μM Rg1 pretreatment for 12 h followed by LPS 1 μg/mL for 6–8 h) groups at the end of respective treatments (n=5 per group).

first: Baihan

last: Sun

first: Kelv

last: Shen

first: Yin

last: Zhu

first: Wenjun

last: Zou


title: Comparative transcriptome profiling of Vitis vinifera cultivar and rootstocks under drought and salinity

city: Eskisehir

first: Saffet

last: Teber

address: Ali Numan Kırac Yerleskesi, Ziraat Caddesi, Odunpazarı/Eskisehir

country: Turkey

institute: Eskisehir Osmangazi University

summary:
Genome-wide expression profiling of Vitis vinifera L. cv. Cabernet Sauvignon (CS) and two rootstocks, Kober 5BB and 41B, exposed to seven days of water deficit or to increasing salinity reaching 120 mM NaCl.
Shoot tissue was profiled on the Affymetrix GeneChip Vitis vinifera Genome Array to identify shared and genotype-specific transcriptional responses to the two stresses.

overall_design: Three genotypes (CS, Kober 5BB, 41B) x three treatments (control, drought, salinity). Shoot tissue pooled from five plants per biological replicate. 54 arrays in total.

first: Melike

last: Bakir

first: Ali

last: Ergul


title: Multimodal spatial profiling reveals distinct myeloid-defined ENKTL subgroups and tumor-myeloid cooperativity within prognostic inflammatory niche

city: singapore

first: Lichang

last: Deng

address: singapore

country: Singapore

institute: NUS

type:
Other
Expression profiling by array

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

overall_design: Refer to individual Series


title: Transcriptomic reprogramming screen identifies SRSF1 as a central regulator of aging and lifespan

city: Boston

first: Alex

last: Plesa

state: MA

address: 77 Avenue Louis Pasteur

department: Genetics

institute: Harvard Medical School

summary: Aging is characterized by progressive functional decline accompanied by distinct transcriptomic and epigenetic alterations. While partial reprogramming via Yamanaka factors can reverse these signatures and improve cell function, safety and efficacy concerns limit their in vivo application, necessitating novel age reversal factors. Here, we develop a functionally interpretable transcriptomic age predictor in human fibroblasts and perform a targeted cDNA overexpression screen to identify interventions that reprogram aged transcriptomes toward youthful states. This screen identifies the RNA-processing and splicing factor SRSF1 as a central regulator of cellular rejuvenation that produces robust youthful transcriptional signatures without loss of cellular identity. In vitro, SRSF1 induction restores youthful phenotypes by reducing senescence, reactive oxygen species, proteostatic stress, and inflammatory signaling. In aged mice, inducible SRSF1 expression reduces frailty progression and increases overall lifespan. Our findings establish SRSF1 as a conserved regulator of organismal aging and a promising therapeutic target for safe in vivo rejuvenation.

overall_design: RNA-seq profiling of wild type normal human dermal fibroblast cells or iPSCs and their derivatives overexpressing different transgenes.

first: Alexandru

first: Sascha

last: Jung

first: Helen

middle: H

last: Wang

first: Fawad

last: Omar

first: Michael

last: Shadpour

first: David

last: ChoyBuentello

first: Maria

middle: C

last: Perez-Matos

first: Naftali

last: Horwitz

first: George

last: Cai

first: ZhenKai

last: Ngian

first: Carol

last: Magalhaes

first: Amy

last: Wagers

first: William

middle: B

last: Mair

first: Antonio

last: del Sol

last: Church


title: KLF4/MLL3 Complex axis Drives NRBP2 Transcription to Eliminate Acute Myeloid Leukemia Cells

city: Tian Jin

first: meng

last: yang

state: Tianjin

address: Nanjing Road No.288

institute: State Key Laboratory of Experimental Hematology, Institute of Hematology & Blood Diseases Hospital

summary: Acute myeloid leukemia (AML) is a heterogeneous malignancy rooted in hematopoietic stem cell dysregulation. Despite therapeutic advances, clinical outcomes remain unsatisfactory. Here, we identify KLF4, a zinc-finger (ZnF) transcription factor with previously reported context-dependent roles in hematologic malignancies, as a negative regulator of AML proliferation. Mechanistically, KLF4 interacts with the MLL3 histone methyltransferase complex, comprising MLL3, WDR5, RBBP5 and ASH2L. KLF4 engages the catalytic subunit MLL3 and the allosteric regulator ASH2L through its ZnF and transrepression (TRD) domains, thereby activating transcription of the tumor suppressor gene NRBP2. Furthermore, integrated transcriptional analysis revealed TNIK as a convergent effector of the KLF4–NRBP2 tumor-suppressive circuit in acute myeloid leukemia. Pharmacological blockade of TNIK with the selective small-molecule inhibitor TNIK-IN-1 selectively impaired leukemic cell proliferation while sparing normal hematopoiesis. Consequently, our findings reveal a previously unrecognized KLF4–MLL3 complex–NRBP2 transcriptional axis that suppresses AML survival through TNIK, highlighting a potential therapeutic strategy for AML.

overall_design: CUT&Tag experiment in combination with the Hyperactive TM In-Situ ChIP Library Prep Kit for Illumina from Vazyme (TD902-01). Cells were captured using ConA beads and subsequently exposed to primary and secondary antibodies in antibody buffer and dig-wash buffer, respectively, according to the manufacturer's instructions. The cells were then incubated with Hyperactive pA808 Tn5 Transposon and fragmented in Tagmentation Buffer at 37°C for 1 h. The extracted DNA fragments were extracted and subjected to high-throughput sequencing.

first: Meng

last: Yang

first: Shangda

first: Ting

last: Lu

first: Hui

last: Cheng

first: Tao


title: Effects of  4 mixture of cytokines including TNF-alpha, IL-1beta IFN-gamma, and TGF-bata1 on rhematoid arthritis synovial fibroblasts

city: Tokyo

first: Tetsuya

last: Saito

state: Tokyo

address: 1-5-45 Yushima Bunkyo-ku

department: Rheumatology

country: Japan

institute: Institute of Science Tokyo

summary: To investigate effects of  4 mixture of cytokines including TNF-alpha, IL-1beta IFN-gamma, and TGF-bata1 on rhematoid arthritis synovial fibroblasts (RASFs), we treated RASFs (n = 3) with TNF-alpha (1 ng/mL), IL-1beta (0.1 ng/mL), IFN-gamma (10 ng /mL), TGF-beta1 (1 ng/mL) (4mix) or vehicle control  (Veh) for 24 hours and conducted RNA-seq analysis.

overall_design: RASFs (n = 3) were treated with TNF-alpha (1 ng/mL), IL-1beta (0.1 ng/mL), IFN-gamma (10 ng /mL), and TGF-beta1 (1 ng/mL) (4mix) or vehicle control  (Veh) for 24 hours. Total RNAs were extracted and subjected to RNA-seq analysis.

first: Motohiko

last: Sato

first: Takahiro

last: Nakahara

first: Shinsuke

last: Yasuda


title: Septin Complexes Regulate Microtubule Organization and Synaptic Function at the Neuromuscular Junction

city: Istanbul

first: Arzu

last: Celik

state: İstanbul

address: Bebek Yolu Sokağı, Kuzey Kampüs, Kuzey Park Binası 304, Etiler

department: Department of Molecular Biology and Genetics

institute: Bogazici University

summary: Septins are GTP-binding cytoskeletal proteins that form filamentous structures and play key roles in cell division, membrane organisation, and cytoskeletal regulation. In Drosophila melanogaster, Septin2 (Sep2) and Septin5 (Sep5) are highly expressed in the nervous system, yet their combined transcriptomic impact remains poorly characterised. Here we performed bulk RNA-seq on w1118 control, Sep2[2] single mutant, Sep5[2] single mutant, and Sep2[2];Sep5[2] double homozygous mutant adult flies to identify synergistic gene expression changes. Differential expression analysis (edgeR, quasi-likelihood) revealed extensive dysregulation of cytoskeletal, microtubule, actin-binding, axon guidance, and signalling gene networks specifically in the double mutant, supporting a functional redundancy model between Sep2 and Sep5.

overall_design: Bulk RNA-seq was performed on whole third instar Drosophila melanogaster larvae. Four genotypes were compared: w1118 (control, n=4), Sep2[2] single mutant (n=3), Sep5[2] single mutant (n=3), and Sep2[2];Sep5[2] double homozygous mutant (n=4). Raw counts were normalised using TMM (edgeR). Differential expression was assessed using quasi-likelihood F-tests. Gene ontology enrichment was performed using clusterProfiler against org.Dm.eg.db.

first: Farzaneh

last: Larti

first: Taha

last: Akkülah

first: Gencay

middle: K

last: Polat

last: Çelik


title: Dual molecular mechanisms and functional compensation by RBMXL1 retrocopy underlie RBMX-associated neurodevelopmental syndrome

city: Illkirch

first: Juliette

last: GODIN

address: 1 rue LAurent Fries

country: France

institute: IGBMC

summary: Genetic variants in RBMX may cause X-linked neurodevelopmental syndromes, but their pathogenicity and mechanisms remain unclear. Here, we provide definitive evidence from nine unrelated families that RBMX variants lead to neurodevelopmental disorders characterised by intellectual disability, brain malformations, microcephaly, and microphthalmia. Combining in vitro and in vivo experiments in human and mouse models, we show that RBMX pathogenic variants disrupt cortical development through both loss- and gain-of-function mechanisms. Despite severe phenotypes in humans, Rbmx-deficient mice display only mild cortical abnormalities, which we attribute to partial compensation by Rbmxl1, a retrocopy that arose independently in mice and humans. We demonstrate that RBMX and RBMXL1 share protein and RNA partners and act redundantly during brain development, with RBMXL1 buffering the effect of RBMX loss. Our findings reveal that RBMX-related neurodevelopmental syndromes result from the interplay of opposing molecular mechanisms and retrocopy compensation, highlighting a previously unrecognized role for retrocopies in modulating disease severity.

overall_design: RNA-seq profiling of Neuro-2a cells transfected with either pCAG-miR30-scramble (miScrambe) or a pool of pCAG-miR30-based miRNAs targeting mouse Rbmx (miRbmx) or Rbmxl1 (miRbmxl1).

first: Pierre

last: Tilliole

first: Carolin

last: Mattausch

first: Peggy

last: Tilly

first: Elsa

last: Leitão

first: Lucile

last: Boutaud

first: Daphné

last: Lehalle

first: Isabelle

last: An

first: Emanuela

last: Argilli

first: Sharon

last: Aufox

first: Bert

last: Callewaert

first: Perrine

last: Charles

first: Jessica K.

last: Cinkornpumin

first: Thomas

last: Courtin

first: Marco

last: Dalla Vecchia

first: Erica

last: Davis

last: Dobyns

first: Ekaterina

last: Epifanova

first: Erwan

last: Grandgirard

first: Matthieu

last: Jung

first: Sarah

last: Jurgensmeyer

first: Sabine

last: Kaya

first: Boris

last: Keren

first: Tahir

last: Khan

first: Elodie

last: Lejeune

first: Mingfeng

last: Li

first: Yannick

last: Marie

first: Bastien

last: Morlet

first: Caroline

last: Nava

first: William A.

last: Pastor

first: Damien

last: Plassard

first: Carlos E.

last: Prada

first: Agnès

last: Rastetter

first: Noémie

last: Schwaller

first: Nenad

last: Sestan

first: Elliott

last: Sherr

first: Suzanna L.

last: Temple

first: Jude-Felix

last: Tenywa

first: Sylvia

last: Tielens

first: Arie

last: van Haeringen

first: Laurent

last: Nguyen

first: Laura

last: Steenpaß

first: Stephan C.

last: Collins

first: Delphine

last: Héron

first: Valerie

last: Cormier-Daire

first: Tania

last: Attie-Bitach

first: Binnaz

last: Yalcin

first: Christel


title: YTHDF1-mediated m6A RNA regulation controls cardiomyocyte remodeling through KLF11-HIF1α [RIP-Seq]

city: Shanghai

first: Lijun

last: Wang

address: 333 Nan Chen Road

institute: Shanghai University

summary: Cardiovascular disease remains the leading cause of mortality globally. While cardiac hypertrophy initially arises as a compensatory adaptation of cardiomyocytes to stress, physiological and pathological cardiac hypertrophy exhibit distinct underlying mechanisms and prognoses. However, the precise mechanisms by which cardiomyocytes differentially respond to various stimuli, resulting in distinct forms of hypertrophy thereby ultimately determining divergent cell fates, remain unclear. Here, we demonstrate that metabolic flexibility governs cardiomyocyte fate during cardiac hypertrophy and identified that this metabolic governance is mediated through YTHDF1-dependent RNA epigenetic regulation. In vivo, cardiomyocyte-specific YTHDF1 deficiency leads to maladaptive cardiac remodeling in response to swimming exercise and additionally exacerbates pathological cardiac remodeling under pressure overload stimulation. In vitro, YTHDF1 functions as a switch to regulate the type of cardiomyocyte hypertrophy in a RNA m6A-dependent manner. The YTHDF1/KLF11/HIF1α axis controls cardiomyocyte fate during hypertrophy via balancing metabolic flexibility to meet energy demands. Cardiac-specific overexpression of YTHDF1 alleviates pathological cardiac remodeling. Our findings reveal a previously unrecognized regulatory pathway wherein YTHDF1 serves as a sensor responding to diverse stresses and controling cardiomyocyte fate during hypertrophy via the YTHDF1/KLF11/Hif1α axis. These results highlight a novel therapeutic approach that may inform the development of exercise intervention strategies, suggesting that enhancing oxidative metabolism may serve as a potential treatment option for cardiac diseases.

overall_design: RNA Immunoprecipitation sequencing (RIP-seq) for YTHDF1 was performed in isolated adult mouse cardiac myocytes.

first: Jiaqi

first: Junjie

last: Xiao


title: Gene expression of two Ewing sarcoma cell lines (SK-N-MC, TC-71), transfected with inducible re-expression of CIAP1

city: Heidelberg

first: Thomas

middle: Georg Philipp

last: Grunewald

address: Im Neuenheimer Feld 280

department: Division of Translational Pediatric Sarcoma Research

country: Germany

institute: German Cancer Research Center (DKFZ)

summary: This dataset comprises trnscriptome data of two Ewing sarcoma cell lines (SK-N-MC and TC-71) after re-expression of the gene CIAP1

overall_design: 4 samples were normalized (log2) with Affymetrix Expression Console Software (v1.4) using SST-RMA algorithm. Gene expression data were annotated at gene level with the Affymetrix library for Clariom D arrays (human).

first: Florencia

last: Cidre-Aranaz

middle: G

last: Grünewald


title: Effect of  homochlorcyclizine dihydrochloride treatment on gene expression in Huh7 hepatocellular carcinoma cells

city: Tianjin

first: 佳仪

last: 吴

address: No.94 Weijin Road

institute: Nankai University

summary: Hepatocellular carcinoma is one of the leading causes of cancer death worldwide.  Our data shows the differentially expressed genes in homochlorcyclizine dihydrochloride treated HCC cells.

overall_design: RNA-seq of profiling of DMSO treated Huh7 cells and homochlorcyclizine dihydrochloride treated Huh7 cells.

first: Jiayi

last: Wu


title: YTHDF1-mediated m6A RNA regulation controls cardiomyocyte remodeling through KLF11-HIF1α (ChIP-seq)

overall_design: Chromatin immunoprecipitation sequencing (ChIP-seq) for KLF11 was performed in isolated adult mouse cardiac myocytes.


title: Coding and non-coding expression profile of in vitro silencing of 3 different lncRNAS in MEC-1 CLL cells

city: Barcelona

first: Lluís

last: Hernández

state: Barcelona

address: Rossello 153

department: Area 5

country: Spain

institute: IDIBAPS

summary:
Silencing in MEC-1 cell line of lncRNA best candidates found to be involved in microenviroment stimulation on primary CLL cells treated ex vivo with CpG-ODN-CD40L+IL10
Samples were normalised (log2) with TAC (v4.0.2) using SST-RMA algorithm

overall_design: Siencing was performed with Gapmer (LNA-oligos) by gymnosis along 4 days comparing 2 specific Gapmers (and the combo) with control scrambled Gapmer, by triplicate.

last: Hernandez


title: Pre-existing chromatin states regulate KLF4 binding to eliminate leukemic cells [mouse ChIP]

first: Kuangyu

last: Yen

address: Nanjing Road

department: State Key Laboratory of Experimental Hematology

institute: Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College

summary: Transcription factors collaborate with chromatin's epigenetic states to regulate cell fate decisions. While recent work suggested that histone modifications could regulate the activity of pioneer transcription factors in vitro, it was unclear whether these findings applied in vivo, or if chromatin states could influence transcription factor binding to affect cell fate. In this work, we identified that H3K18ac, a potential caner-related histone mark, could regulate Klf4's genomic binding, thereby affecting divergent cellular destinies in leukemia cells and HSPCs. This unveils prospective opportunities for applying transcription factors combined with epigenetic markers in clinical applications. In summary, our results suggest that pre-existing chromatin states could regulate transcription factor binding in vivo, and therefore influence the cell fate decision.

overall_design: ChIP-seq for Klf4 in AML(MLL-AF9) and HSPC(ckit+) cells

first: Ting

last: Lu

first: Shangda

last: Yang

first: Cong

last: Chen

first: Hui

last: Cheng

first: Tao


title: Pre-existing chromatin states regulate KLF4 binding to eliminate leukemic cells (ATAC-Seq)

overall_design: To investigate the chromatin accessibility changes for the elimination of leukemia cells after Dox inducible Klf4 expression, we sorted GFP+ MLL-AF9 acute myeloid leukemia cells (MLL-AF9) from leukemic mice. Leukemia cells were sorted from distinct groups at different time points


title: Transcriptomic reprogramming screen identifies SRSF1 as a central regulator of aging and lifespan - EPIC

first: Alex

last: Plesa

type: Methylation profiling by genome tiling array

overall_design: Illumina array DNAm profiling of normal human dermal fibroblast cells treated with rapamycin or overexpressing different transgenes and mouse liver from AAV gene therapy experiments

first: Alexandru

first: Sascha

last: Jung

first: Helen

first: Fawad

last: Omar

first: Michael

last: Shadpour

first: David

last: ChoyBuentello

first: Maria

last: PerezMatos

first: Naftali

last: Horwitz

first: George

last: Cai

first: ZhenKai

last: Ngian

first: Carol

last: Magalhaes

first: Amy

last: Wagers

first: William

last: Mair

first: Antonio

last: delSol

last: Church


title: Effects of pan-TEAD inhibitor K975 on rhematoid arthritis synovial fibroblasts

first: Tetsuya

last: Saito

summary: To investigate effects of pan-TEAD inhibitor K975 on rhematoid arthritis synovial fibroblasts (RASFs), we treated RASFs (n = 3) with K975 (0.5 microM) for 24 hours and conducted RNA-seq analysis.

overall_design: RASFs (n = 3) were  treated with K975 (0.5 microM) or vehicle control  (Veh) for 24 hours. Total RNAs were extracted and subjected to RNA-seq analysis.

first: Motohiko

last: Sato

first: Takahiro

last: Nakahara

first: Shinsuke

last: Yasuda


title: Single cell RNA and TCR profiling of liver transplant patients peripheral blood mononuclear cells

city: Seoul

first: Byungjin

last: Hwang

address: 50-1, Yonsei-ro, Seodaemun-gu

country: South Korea

institute: Yonsei University

summary: To explore immune cell dynamics in allograft rejection in LT patients, paired PBMC samples from pre- and post-operative blood of recipients who experienced acute rejection and those without rejection were sequenced.

overall_design: To analyze transcriptomic profile at the time of rejection, samples most immediately collected after biopsy-proved or empirical diagnosis were selected as Post-AR samples among those collected at 1 week, 2 weeks, 1 month, and 2 months after the operation. The time points of the Post-NR sample were matched to that of each Post-AR sample.

first: Dong Jin

last: Joo

first: Deok Gie

last: Kim

first: Su-Hyeon

last: Lee

first: Yuri

last: Cho


title: KLF4/MLL3 Complex axis Drives NRBP2 Transcription to Eliminate Acute Myeloid Leukemia Cells [Cut & Tag]

first: meng

last: yang

first: Meng

last: Yang

first: Shangda

first: Ting

last: Lu

first: Hui

last: Cheng

first: Tao


title: A family of small proteins connects c-di-GMP-signaling with sporulation in the human pathogen Clostridioides difficile

city: Gif-sur-Yvette

first: Johann

last: PELTIER

address: avenue de la Terrasse

institute: I2BC, CNRS

summary: Cyclic diguanosine monophosphate (c-di-GMP) is a ubiquitous bacterial second messenger that coordinates lifestyle transitions, virulence, and developmental processes. In Clostridioides difficile, elevated c-di-GMP levels inhibit sporulation, but the underlying mechanism remained unclear. Here, we identified a conserved family of small, membrane-associated proteins as previously unrecognized effectors of c-di-GMP signaling. Their expression is controlled by class I c-di-GMP-responsive riboswitches. Transcriptomic analyses revealed that c-di-GMP represses these genes, and reporter assays demonstrated riboswitch-dependent transcriptional regulation via premature termination mechanism. Overexpression of a single member, CD1980.2, was sufficient to trigger the transcriptional activation of sporulation genes, including sigma factors and their regulons, and to increase spore formation. Conversely, sporulation efficiency decreased proportionally with the number of deleted small protein genes, and the strain lacking all seven genes displayed a severe sporulation defect, underscoring their cumulative and functionally redundant roles. Elevating c-di-GMP levels in the deletion mutant did not further reduce sporulation, supporting a model in which c-di-GMP inhibits spore formation by repressing the expression of this small-protein family.  Our work establishes these small proteins as critical effectors linking c-di-GMP signaling to developmental output in C. difficile. Their redundancy, conservation, and integration into riboswitch- and RgaR-mediated regulatory pathways highlight their central role in spore formation, a process essential for pathogen persistence and transmission.  These findings expand the repertoire of second-messenger effectors in bacterial physiology.

overall_design: RNA-seq profiling of Clostridioides difficile 630∆erm strain and the derivative strain Ptet-dccA with chromosomal insertion of the Ptet promoter upstream dccA. RNA-seq profiling of Clostridioides difficile 630∆erm strain ∆Cdi1_6-CD1980.2 carrying  an empty plasmid (p) or a plasmid expressing Cdi1_6-CD1980.2 under control of the Ptet promoter (pCCdi1_6-CD1980.2). Strains were grown in TY with 250 ng/ml ATc for 7 h.

first: Adriana

last: Badilla Lobo

first: Olga

last: Soutourina

last: Peltier


title: Coding and non-coding expression profile of ex vivo treated CLL primary cells

first: Lluís

last: Hernández

summary:
Samples were splitted in 4 conditions: (A) control without Agonist mix and with NGS beads, (B) control with Agonist mix and NGS beads, (C) With Agonist mix and NGS beads, (D) With Agonist mix and IGM beads. Agonist mix (microenviroment stimuli): CpG-ODN2006-CD40L+IL10
Samples were normalised (log2) with TAC (v4.0.2) using SST-RMA algorithm

overall_design:
Samples were splitted in 4 conditions: (A) control without Agonist mix and with NGS beads, (B) control without Agonist mix and IgM beads+Ibrutinib, (C) With Agonist mix and NGS beads, (D) With Agonist mix and IGM beads+Ibrutinib. Agonist mix (microenviroment stimuli): CpG-ODN2006-CD40L+IL10

Please note that the sample titles represent
[1] sample origin (depending on the lab involved; one from Barcelona-BCN (Spain) and the other from Aviano-AVI (Italy), as indicated in the sample descripition field),
[2] subtype of the studied disease, WT or the other subtypes carrying genetic alterations as TP53 alterations or Trisomy 12 alterations,
[3] experimental condition

last: Hernandez


title: Effects of  TEAD4 knockdown on rhematoid arthritis synovial fibroblasts stimulated with 4 mixture of cytokines including TNF-alpha, IL-1beta IFN-gamma, and TGF-bata1

first: Tetsuya

last: Saito

summary: To investigate effects of  TEAD4 knockdown on rhematoid arthritis synovial fibroblasts (RASFs) stimulated with 4 mixture of cytokines including TNF-alpha, IL-1beta IFN-gamma, and TGF-bata1 , we pre-treated RASFs (n = 3) with siControl (siCtrl) or siTEAD4 for 72 hours, and then treated them with TNF-alpha (1 ng/mL), IL-1beta (0.1 ng/mL), IFN-gamma (10 ng /mL), TGF-beta1 (1 ng/mL) (4mix) for 24 hours and conducted RNA-seq analysis.

overall_design: RASFs (n = 3) were pre-treated with siCtrl or siTEAD4 for 72 hours, and treated with TNF-alpha (1 ng/mL), IL-1beta (0.1 ng/mL), IFN-gamma (10 ng /mL), and TGF-beta1 (1 ng/mL) (4mix) or vehicle control  (Veh) for 24 hours. Total RNAs were extracted and subjected to RNA-seq analysis.

first: Motohiko

last: Sato

first: Takahiro

last: Nakahara


title: PNET2_A and PNET2_B function redundantly with CRWN protein.

city: beijing

first: xiao

last: liu

address: yiheyuan road 5, Haidian

institute: peking university

summary: Purpose: To understand the molecular mechanism between PNET2 and CRWNs, we generated higher-order mutants of crwn1;4pnet2_a, crwn1;4 pnet2_b, and compare them with wild-type, crwn1;4 using whole genome transcriptome analysis on 4-week-old plants.

overall_design: mRNA profiles of 4-week-old plants of wild type (Col-0), crwn1;4, crwn1;4 pnet2_a, crwn1;4 pnet2_b mutants were generated by deep sequencing, in triplicate, using Illumina HiSeq 2000.

first: Yu

last: Tang

first: Xiao

last: Liu


title: Transcriptomic profiling of hemin-treated bone marrow-derived macrophages in a TGF-β1-induced macrophage–renal tubular epithelial cell co-culture model

status: Public on Aug 14 2026

city: shanghai

first: Yiqi

last: Ma

address: Department of Radiology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, No.197, Ruijin 2nd Road, Shanghai, China.

institute: Ruijin hospital, shanghai jiaotong university school of medicine

summary: Kidney fibrosis is characterized by persistent activation of renal tubular epithelial cells and extensive remodeling of the immune microenvironment. Macrophages are highly plastic cells that respond to metabolic and inflammatory signals and may regulate the progression of renal fibrosis. This study investigated the transcriptional changes induced by hemin in bone marrow-derived macrophages in a macrophage–renal proximal tubular epithelial cell co-culture system. Mouse bone marrow-derived macrophages were co-cultured with primary renal proximal tubular epithelial cells using a Transwell system. Renal tubular epithelial cells were exposed to transforming growth factor beta 1 (TGF-β1) to establish a profibrotic microenvironment, with or without hemin treatment. After treatment, macrophages were collected for bulk RNA sequencing. Transcriptomic analysis showed that hemin altered macrophage pathways associated with heme and iron metabolism, antioxidant responses, glutathione metabolism, inflammatory signaling, extracellular matrix regulation, and cellular metabolism. These data provide insight into the macrophage transcriptional reprogramming associated with the protective effects of hemin against renal fibrosis.

overall_design: Primary renal proximal tubular epithelial cells and mouse bone marrow-derived macrophages were cultured in a Transwell co-culture system, with renal tubular epithelial cells in the lower chamber and macrophages in the upper insert. A profibrotic microenvironment was induced using TGF-尾1. Samples were divided into two experimental conditions: TGF-尾1 treatment and TGF-尾1 plus hemin treatment. TGF-尾1 was used at 5 ng/mL, and hemin was used at 10 渭M. After 72 hours of treatment, bone marrow-derived macrophages were collected from the Transwell inserts, and total RNA was extracted for bulk RNA sequencing. Gene expression profiles were compared between the TGF-尾1 plus hemin group and the TGF-尾1 group to identify hemin-induced transcriptional changes in macrophages.

first: Qian

last: Wu


title: CHTOP Regulates ROS Homeostasis to Modulate Chemoresistance in Colorectal Cancer

city: xi’an

first: mingchao

last: mu

state: Shannxi

address: No. 277 Yanta West Road, Yanta District, Xi'an City, Shaanxi Province

institute: xi'an jiaotong university

summary: Chemotherapy resistance remains a significant challenge in colorectal cancer (CRC) treatment, with disrupted reactive oxygen species (ROS) homeostasis playing a central role. We identify CHTOP as a key regulator of ROS levels and chemoresistance in CRC. Mechanistically, CHTOP regulates ROS homeostasis by interacting with Nrf2 and modulating its SUMOylation via the SENP3-containing 5FMC complex. Notably, CHTOP expression is tightly controlled by a ROS-dependent feedback loop. The PSIP1/p52 isoform inhibits CHTOP expression by disrupting HNRNPH1-dependent splicing, leading to CHTOP degradation via nonsense-mediated decay (NMD). Meanwhile, ROS accumulation stabilizes SENP3, promoting the deSUMOylation and degradation of p52, thereby forming a ROS-SENP3-p52-CHTOP feedback loop. Thus, ROS levels both regulate and are regulated by CHTOP, maintaining redox balance. CHTOP downregulation in 5-FU-resistant CRC shifts cells into a higher-ROS steady state, which correlates with reduced 5-FU sensitivity. Both restoring CHTOP expression and inducing further depletion of CHTOP disrupt redox balance in 5-FU-resistant cells, reversing resistance and re-establishing sensitivity. These findings suggest that modulating CHTOP expression may offer a promising therapeutic strategy to overcome chemoresistance in CRC through redox regulation.

overall_design: Analysis of RNA-seq data comparing control and CHTOP knockdown in HCT116 cells.

first: Mingchao

last: Mu

first: Jing

last: Li


title: KLF4/MLL3 axis Drives NRBP2 Transcription to Eliminate Acute Myeloid Leukemia Cells

first: meng

last: yang

summary: Acute myeloid leukemia (AML) is a heterogeneous malignancy rooted in hematopoietic stem cell dysregulation. Despite therapeutic advances, clinical outcomes remain unsatisfactory. Here, we identify KLF4, a zinc-finger (ZnF) transcription factor with previously reported context-dependent roles in hematologic malignancies, as a negative regulator of AML proliferation. Mechanistically, KLF4 interacts with the MLL3 histone methyltransferase complex, comprising MLL3, WDR5, RBBP5 and ASH2L. KLF4 engages the catalytic subunit MLL3 and the allosteric regulator ASH2L through its ZnF and transrepression (TRD) domains, thereby activating transcription of the tumor suppressor gene NRBP2. Furthermore, integrated transcriptional analysis revealed TNIK as a convergent effector of the KLF4–NRBP2 tumor-suppressive circuit in acute myeloid leukemia. Pharmacological blockade of TNIK with the selective small-molecule inhibitor TNIK-IN-1 selectively impaired leukemic cell proliferation while sparing normal hematopoiesis. Consequently, our findings reveal a previously unrecognized KLF4–MLL3 complex–NRBP2 transcriptional axis that suppresses AML survival through TNIK, highlighting a potential therapeutic strategy for AML.

overall_design: RNA-seq profiling of overexpression KLF4 and NRBP2 in THP-1 cells

first: Meng

last: Yang

first: Cong

last: Chen

first: Shangda

first: Hui

last: Cheng


title: Sublethal envelope-targeting silver nanoparticles induce ethanolamine-mediated cross-feeding and stabilize competitive pathogens

city: Beijing

first: Rui

last: Sun

address: No.19, Xinjiekouwai St

department: School of Environment

institute: Beijing Normal University

summary: Envelope-targeting antimicrobials are widely detected in wastewater and engineered water systems, yet their potential to reshape interspecies interactions through membrane-derived metabolites remains poorly understood. Here, we investigated whether sublethal silver nanoparticles (AgNPs) could bias competitive interactions between Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus) toward more balanced coexistence. Repeated exposure to 0.5 mg/L AgNPs for 9 days increased the S. aureus/E. coli ratio threefold. In contrast, untreated co-cultures were dominated by E. coli, with 25% of lineages showing competitive exclusion and an E. coli/S. aureus ratio exceeding 10³ . During competition with S. aureus, E. coli activated ethanolamine (EA) utilization in bacterial microcompartments (Eut BMCs), resulting in extracellular accumulation of acetate and ammonium. Physiological assays identified nitrogen, rather than carbon, as the principal growth-promoting currency of this cross-feeding interaction. Deletion of eutBC in AgNP-exposed cocultures abolished the coexistence phenotype and restored an outcome similar to that observed in the absence of AgNP exposure. In simulated eutrophic water, sublethal AgNPs also enhanced S. aureus survival through the E. coli Eut pathway, supporting the environmental relevance of this mechanism. Mass-matched Ag⁺ exposure neither induced EA utilization nor promoted more balanced coexistence. These findings indicate that sublethal envelope-targeting nanomaterials can alter microbial metabolism and competitive relationships in this two-species model, with potential implications for interactions in contaminated water systems.

overall_design: In the co-culture system, E. coli and S. aureus were grown to stationary phase in TSB medium and mixed equally. This mixture was then inoculated at 1% into 500 μL of TSB medium, with three different treatments: (1) no additive, (2) 0.5 mg/L AgNPs, and (3) 0.5 mg/L Ag+. Each condition had 24 replicates. Monocultures of E. coli and S. aureus were also cultivated separately under each of the three conditions, with 9 replicates for each treatment. All cultures were kept in 96-well deep plates at 37 °C with shaking at 160 rpm. Every 24 h, 1% of the culture was transferred to fresh medium under the same conditions until a dominant species emerged in the co-culture system, over a total period of 9 days.

first: Tianmin


title: Transcriptome of liver transplant patients peripheral blood mononuclear cells

first: Byungjin

last: Hwang

summary: To explore immune cell dynamics in allograft rejection in LT patients, PBMC samples from recipients who experienced acute rejection and those without rejection were sequenced.

overall_design: This dataset contains bulk sequencing data from pre-operative PBMC samples and was used to generate reference genotypes for Souporcell analysis in conjunction with single-cell transcriptomic data collected before and after surgery.

first: Dong Jin

last: Joo

first: Deok Gie

last: Kim

first: Su-Hyeon

last: Lee

first: Yuri

last: Cho


title: Effect of CBP/P300 inhibition on extravillous trophoblast differentiation

city: Amsterdam

first: Remco

last: Keijser

address: Meibergdreef 9

department: Reproductive Biology Laboratory

country: Netherlands

institute: Amsterdam UMC

summary: Treatment of trophoblast stem cells (TSCs) with the CBP/P300 inhibitors A‑485 and CPI blocks their differentiation into extravillous trophoblasts (EVTs) and syncytiotrophoblasts. In this project, we examine how these inhibitors affect gene expression dynamics during EVT differentiation.

overall_design: TSCs were seeded either in TSC medium or in EVT‑A medium, with or without 1 µM A‑485 or 3 µM CPI. On day 3, TSCs were collected for RNA isolation, while EVTs were refreshed with EVT‑B medium, again with or without 1 µM A‑485 or 3 µM CPI. EVTs were harvested for RNA isolation on day 5. A detailed culture protocol is provided in van Voorden et al., 2023 (DOI: 10.1073/pnas.2217405120).  The samples included in the current sequence submission are the EVTs cultured in the presence of inhibitor. The corresponding TSCs and EVTs grown without inhibitor are available under GEO accession GSE282356. TSC samples: GSM8641822, GSM8641824, and GSM8641834. EVT samples: GSM8641823 and GSM8641829.

first: Fangxu

last: Lin

first: Souad

last: Boussata

first: Gijs

last: Afink


title: Transcriptome profile of hypergravity-induced enhanced wheat root growth

city: Dharwad

first: Ravikumar

last: Hosamani

state: Karnataka

address: Krishinagar

department: Biotechnology

country: India

institute: UAS-Dharwad

summary: We report for the first time the transcriptome profiling of hypergravity-induced enhanced wheat root growth phenotype. Hypergravity, specifically 10g for 12hrs induced enhanced root length phenotype in greenhouse conditions. We investigated the molecular basis of this altered phenotype through whole transcriptome analysis. We identified the differentially expressed transcripts, gene ontology terms, transcription factors, and candidate genes that could be attributed to the enhanced root growth phenotype. Based on this transcriptome data, we also proposed a model describing the mechanism of hypergravity-induced root growth phenotype in wheat.

overall_design: mRNA profiles of 45-day-old roots in control and hypergravity treatment (10g for 12 hrs)

first: Malarvizhi

last: Sathasivam

first: Basavalingayya

last: Swamy

first: Kushagra

last: Krishnan

first: Rita

last: Sharma

first: Spurthi

last: Nayak

first: D

last: Uppar


title: m6A depletion attenuates the macrophage type I interferon response

city: Boulder

first: Edward

last: Courvan

address: 3415 Colorado Ave

institute: University of Colorado

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

overall_design: Refer to individual Series


title: Pre-existing chromatin states regulate KLF4 binding to eliminate leukemic cells

first: Kuangyu

last: Yen

overall_design: To investigate the gene expression changes for the elimination of leukemia cells after Dox inducible Klf4 expression, we sorted GFP+ MLL-AF9 acute myeloid leukemia cells (MLL-AF9) from leukemic mice. Leukemia cells were sorted from distinct groups at different time points

first: Ting

last: Lu

first: Shangda

last: Yang

first: Cong

last: Chen

first: Hui

last: Cheng

first: Tao


title: Single-cell Transcriptomics Reveals the Heterogeneous Landscape of Innate Lymphoid Cells in Zebrafish

city: Shenzhen

first: Zilong

last: WEN

institute: Southern University of Science and Technology

summary: Innate lymphoid cells (ILCs) are a class of lymphocytes whose activation is independent of antigen receptors. They constitute a major lymphocyte compartment and likely play a prominent role in lower vertebrates, though their precise composition and functions remain poorly characterized. Here, using scRNA-seq, we identify a broad spectrum of distinct ILC subsets, including both conventional subsets resembling their mammalian counterparts and unconventional ILC-like populations with unique features and distinct tissue distributions. We demonstrate that the complete ILC repertoire emerges early in development, independent of hematopoietic stem cells (HSCs), yet is maintained into adulthood via an HSC-dependent mechanism. Our work defines the landscape and ontogeny of zebrafish ILCs, revealing their underappreciated diversity and providing key insights into vertebrate innate immunity evolution.

overall_design: scRNA-seq (10X genomics 3’ V3.1) of coro1a+ cells sorted from Tg(coro1a:eGFP) in both wild type and rag1 mutant background. eGFP+ leukocytes were collected from whole fish at 1-month-old age , dissected intestines and dissected scales (epidermis) at 3-month-old age under both genetic backgrouds. HSC-indepentent coro1a+ cell were isolated fromTg(hsp70l:mCherry-T2a-CreERT2;coro1a:loxp-DsRedx-loxp-eGFP) at 2-week old.

first: Kefan

first: Thi Huong

last: Trinh

first: Ying

last: Cao

first: Shachuan

last: Feng

first: Jiaxin

last: Liang

first: Shizheng

last: Zhao

first: Jiaxu

last: Yin

last: Dong

last: Wen


title: Engineering Large Meniscal Tissues via 3D Printed Multipart Molds

first: Jason

last: Burdick

state: Colorado

address: 3415 Colorado Avenue

department: BioFrontiers Institute

institute: University of Colorado, Boulder

summary: The menisci are highly organized fibrocartilaginous tissues that provide load distribution, shock absorption, and joint lubrication in the knee. Unfortunately, the meniscus is commonly injured, and due to the low intrinsic healing capacity of the meniscus, surgical intervention is often required to treat acute symptoms. However, current treatments such as partial meniscectomy or tissue replacement with clinically available scaffolds – all of which lack the anisotropic organization of the native meniscus – are inadequate. Here, we present the engineering of highly organized meniscal tissues using 3D printed hydrogel molds to guide organization of a cell-laden collagen gel. Utilizing an inexpensive 3D printer ($270 USD), we introduce the fabrication of large multipart hydrogel molds with removeable lengthwise walls. We screen seven unique starting formulations in which mold depth, collagen density, and cell concentration are modulated and resultant biochemical and mechanical properties are assessed. After 28 days in culture, the engineered tissues meet or exceed the tensile modulus of 1-week old bovine menisci – a multifold improvement over the tensile moduli of all other collagen-based day 28 engineered tissues to our knowledge. Towards the goal of developing an implantable therapeutic, we demonstrate that the suture retention strength of the day 14 engineered tissues is comparable to that of the clinically available isotropic collagen meniscus implant. Finally, we show that the engineered tissues promote enhanced integration with native meniscus tissue ex vivo relative to native tissue alone. Taken together, these results are an exciting step towards improving meniscal repair using tissue engineering strategies.

overall_design: RNA-seq profiling of Day 28 engineered meniscal tissues (with and without post anchors, divided into middle and post regions) as well as "blobs" (cells in collagen with no mold).

first: Alysse

middle: T

last: DeFoe

first: Seth

last: Ack

first: Arkodip

last: Mandal

first: Braden

last: Johnson

first: Lorin

last: Danielson

first: Robert

middle: L

last: Mauck

middle: A