Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Mesenchymal stem cell–derived extracellular vesicles alleviate immunoparalysis in sepsis-associated ARDS via reprogramming the lactate–H3K18 lactylation–PSMD14 axis

ABSTRACT: Sepsis-associated acute respiratory distress syndrome (S-ARDS) is characterized by immune dysfunction and high mortality. Here, we show that elevated lactate induces P300-dependent H3K18 lactylation, which enhances PSMD14 transcription. Increased PSMD14 activates the AKT/mTOR pathway, leading to macrophage immunosuppression, including reduced inflammatory cytokine production, impaired phagocytosis, increased M2 polarization, and T cell dysfunction.Integrated analyses of public datasets, RNA-seq, and ChIP-seq identified PSMD14 as a key immune-related gene associated with poor outcomes and reduced HLA-DR expression in patients. Extracellular vesicles derived from P300 inhibitor (C646)-preconditioned mesenchymal stem cells suppress the H3K18la–PSMD14 axis, restore immune function, and improve survival.

ORGANISM(S): Homo sapiens

PROVIDER: GSE327100 | GEO | 2026/04/07

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

BRD9 Reads Lactate-Induced H3K18 Lactylation to Drive Oncogenic Chromatin Remodeling in Hepatocellular Carcinoma

Project description:Histone lactylation bridges glycolytic metabolism to oncogenic transcription, but its mechanistic readers remain poorly defined. Here, we identify bromodomain-containing protein 9 (BRD9) as a lactyl-lysine reader that links lactate-driven H3K18 lactylation (H3K18la) to chromatin remodeling in hepatocellular carcinoma (HCC). Clinically, elevated H3K18la levels correlate with poor HCC prognosis. Structural (NMR) and biophysical analyses demonstrate BRD9’s bromodomain engages H3K18la through its acetyl-lysine pocket with weak, transient affinity, distinct from stable H3K18ac binding, enabling lactate-dependent chromatin interactions. Multi-omics profiling reveals H3K18la recruits BRD9 and the non-canonical BRG1-associated factor (ncBAF) complex to active enhancers and promoters, promoting chromatin accessibility and oncogenic transcription (SPARC, TMEM64, ANGEL1, SCARB1). Glycolytic inhibition or BRD9 targeting displaces BRD9 from chromatin, suppresses oncogenes, and impairs HCC proliferation. p300 or HDAC inhibition attenuates H3K18la-driven oncogenic transcription and tumor viability. Our findings establish BRD9 as a metabolic-epigenetic mediator that translates glycolytic flux into chromatin remodeling, offering actionable therapeutic targets for HCC.

2026-03-05 | GSE314155 | GEO

Lactate-Induced H3K18 Lactylation Drives CX3CL1-Mediated Immune Cell Recruitment in Sepsis-Associated ARDS

Project description:Sepsis is characterized by lactate accumulation and immune dysfunction, but the molecular mechanisms linking lactate to chemokine expression remain unclear. Here, we investigated whether lactate regulates chemokine transcription through histone lactylation. Human peripheral blood mononuclear cells (PBMCs) were treated with lactate (LAC group) or PBS control (CON group), followed by RNA sequencing (RNA-seq) to identify differentially expressed genes. Chromatin immunoprecipitation sequencing (ChIP-seq) using H3K18la-specific antibody was performed to detect lactylation-enriched gene promoters. Integration of RNA-seq and ChIP-seq data identified CX3CL1 as a lactylation-regulated chemokine. Functional assays demonstrated that lactate-induced H3K18la promotes CX3CL1 expression, enhances PBMC migration, and facilitates T cell recruitment in vitro. In a cecal ligation and puncture (CLP)-induced sepsis-associated acute respiratory distress syndrome (ARDS) mouse model, elevated lactate increased pulmonary CX3CL1 expression and immune cell infiltration, whereas inhibition of lactate production reduced these effects. These data reveal a lactate–H3K18la–CX3CL1 axis that mediates immune cell recruitment and exacerbates sepsis-related lung injury.

2026-04-22 | GSE328660 | GEO

Mesenchymal stem cell–derived extracellular vesicles alleviate immunoparalysis in sepsis-associated ARDS via reprogramming the lactate–H3K18 lactylation–PSMD14 axis

Project description:Mesenchymal stem cell–derived extracellular vesicles alleviate immunoparalysis in sepsis-associated ARDS via reprogramming the lactate–H3K18 lactylation–PSMD14 axis

| PRJNA1449442 | ENA

p300-Mediated Histone H3K18 Lactylation Promotes Mitochondrial ROS Accumulation via Mitophagy Inhibition to Potentiate Dopamine Agonists Efficacy in Prolactinomas [CUT&Tag]

Project description:Prolactinomas are the most common functional pituitary adenomas, with dopamine receptor agonists (DAs) as the first-line therapy. However, 10–30% of patients develop DA resistance, and the underlying mechanisms remain incompletely elucidated.Clinical samples were collected to analyze p300 expression. Experiments including immunofluorescence, immunohistochemistry, gene editing, Western blot, co-immunoprecipitation, ChIP-qPCR, RNA/CUT&Tag sequencing, flow cytometry, Seahorse assay, and mass spectrometry were performed to explore the synergistic anti-tumor mechanism of upregulating/activating p300 combined with DAs. DAs downregulated p300 by inhibiting the cAMP-PKA-CREB pathway. Upregulating/activating p300 synergized with DAs to promote mitochondrial ROS elevation and cell apoptosis, which depends on p300’s histone acetyltransferase (HAT) domain mediating histone H3 lysine 18 lactylation (H3K18la). p300-mediated H3K18la significantly promoted intracellular ROS accumulation by upregulating Ndufs7 (promoting mitochondrial ROS production) and Washc1 (inhibiting mitophagy). YF-2, a p300 HAT domain activator, exhibited synergistic anti-tumor activity with DAs.This study reveals the p300-H3K18la- mitophagy-ROS regulatory axis, providing a new target and strategy for treating DA-resistant prolactinomas.

2026-03-11 | GSE313568 | GEO

p300-Mediated Histone H3K18 Lactylation Promotes Mitochondrial ROS Accumulation via Mitophagy Inhibition to Potentiate Dopamine Agonists Efficacy in Prolactinomas [RNA-seq]

2026-03-11 | GSE313569 | GEO

Lactate-driven H3K18 lactylation promotes cisplatin resistance in bladder cancer via HNRNPF-Parkin mediated mitophagy

Project description:Cisplatin resistance in bladder cancer (BCa) is driven by metabolic reprogramming that enhances glycolysis and lactate production. Here, we report that lactate-induced histone H3K18 lactylation (H3K18la) drives chemoresistance by activating a novel signaling axis that couples epigenetic regulation with mitochondrial quality control. Through integrative multi-omics analysis, we identified HNRNPF as a key effector downstream of H3K18la, with its promoter being directly enriched by H3K18la in cisplatin-resistant BCa cells. Unexpectedly, HNRNPF, primarily known as an RNA-binding protein, promotes chemoresistance through a non-canonical mechanism: it directly interacts with the core mitophagy protein Parkin. Mechanistically, the RRM2 domain of HNRNPF binds the R0 domain of Parkin, facilitating Parkin’s recruitment to damaged mitochondria. This interaction potentiates Parkin’s E3 ubiquitin ligase activity, leading to enhanced ubiquitination of VDAC1 and robust activation of mitophagy. Collectively, our findings establish the H3K18la-HNRNPF-Parkin axis as a previously unrecognized signaling cascade that bridges epigenetic reprogramming with to mitochondrial quality control in chemoresistance. Targeting this axis, particularly the HNRNPF-Parkin interaction or mitophagy activation, may represent a novel therapeutic strategy to overcome cisplatin resistance in BCa, pending further validation in preclinical models.

2026-03-30 | GSE325983 | GEO

Lactate-p300 activates macrophage-fibroblast-like synoviocytes communication via H3K18la to promote rheumatoid arthritis

Project description:This study investigated the role of lactate‑induced histone H3K18 lactylation (H3K18la) in the pathology of rheumatoid arthritis (RA).Immunohistochemistry, western blot, gene knockdown/overexpression, proteomics, transwell co‑culture, and flow cytometry were employed to explore the function and mechanism of H3K18la in RA.Results demonstrated that elevated lactate levels in M1 macrophages promote H3K18la through p300, leading to the upregulation of METTL16 in these macrophages.When co‑cultured with M1 macrophages, fibroblast‑like synoviocytes (FLS) showed enhanced Wnt/β‑catenin signaling (increased expression of Wnt1) and elevated levels of pro‑invasive markers including MMP3 and fibronectin. These effects were abolished by p300 knockdown in macrophages, but restored by enforced overexpression of METTL16.In conclusion, lactate‑p300‑mediated H3K18la in M1 macrophages drives RA progression via METTL16/Wnt1‑dependent crosstalk with FLS, linking lactate metabolism and histone lactylation in M1 macrophages to the pathogenesis of RA.

2026-03-04 | PXD075185 |

Lactate-Induced H3K18 Lactylation Drives CX3CL1-Mediated Immune Cell Recruitment in Sepsis-Associated ARDS

Project description:Lactate-Induced H3K18 Lactylation Drives CX3CL1-Mediated Immune Cell Recruitment in Sepsis-Associated ARDS

| PRJNA1456091 | ENA

Expression profile of melanoma cells following p300 HAT inhibition

Project description:Epigenetic events, including covalent post-translational modification of histones, have frequently been demonstrated to play critical roles in tumor development and progression. The transcriptional coactivator, p300/CBP, possesses both histone acetyltransferase (HAT) activity as well as scaffolding properties that directly influence transcriptional activation of targeted genes. We have used a recently reported small molecule inhibitor of p300 HAT activity, C646, to explore the specific contribution of p300/CBP HAT activity to tumor development and progression. We find that C646 inhibits the growth of lineage-specific tumor cell lines including human melanomas through direct transcriptional regulation of cell cycle regulatory proteins. Further evaluation of the p300 HAT transcriptome in human melanoma cells using comprehensive gene expression profiling reveals that p300 HAT activity globally promotes cell cycle progression, nucleosome assembly, and the DNA damage checkpoint through direct transcriptional regulatory mechanisms. Additionally, C646 promotes sensitivity to DNA damaging agents leading to enhanced apoptosis of melanoma cells following combination treatment with cisplatin. Together our data suggest that p300 HAT activity regulates critical growth regulatory pathways in tumors and may serve as a novel therapeutic target for melanoma and other malignancies by promoting cellular responses to DNA damaging agents. Keywords: p300, small molecule inhibitor, melanoma WM35 cells grown under normal culture conditions were treated for 6 and 24 hours with compound C646 to block p300 HAT activity. A vehicle control (DMSO) was included at each time point. RNA was extracted from all 4 samples using the Qiagen RNeasy kit. RNA quality check, labeling, hybridization, initial data processing and analysis was performed by the JHMI Microarray Core Facility. Affymetrix GeneChip Human Exon 1.0 ST Array was used for this study.

2013-08-01 | E-GEOD-45981 | biostudies-arrayexpress

Dynamic methylation of histone H3K18 in differentiating Theileria parasites

Project description:Lysine methylation on histone tails impacts genome regulation and cell fate determination in many developmental processes. Apicomplexa intracellular parasites cause major diseases and they have developed complex life cycles with fine-tuned differentiation events. Yet, apicomplexa genomes have few transcription factors and little is known about their epigenetic control systems. Tick-borne Theileria apicomplexa species have relatively small, compact genomes and a remarkable ability to transform leukocytes in their bovine hosts. Here we report enriched H3 lysine 18 monomethylation (H3K18me1) on the gene bodies of repressed genes in Theileria macroschizonts. Differentiation to merozoites (merogony) led to decreased H3K18me1 in parasite nuclei. Pharmacological manipulation of H3K18 acetylation or methylation impacted parasite differentiation and expression of stage-specific genes. Finally, we identified a parasite SET-domain methyltransferase (TaSETup1) that can methylate H3K18 and represses gene expression. Thus, H3K18me1 emerges as an important epigenetic mark which controls gene expression and stage differentiation in Theileria parasites.

2021-03-25 | PXD024599 | Pride

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data