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Epigenetic dosage identifies two major and functionally distinct β cell subtypes

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

ORGANISM(S): Mus musculus

PROVIDER: GSE224061 | GEO | 2023/02/16

REPOSITORIES: GEO

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Epigenetic dosage identifies two major and functionally distinct β cell subtypes [DNAmethArray]

Project description:The mechanisms that specify and stabilize cell subtypes remain poorly understood. Here, we identify two major subtypes of pancreatic β cells based on histone mark heterogeneity (βHI and βLO). βHI cells exhibit ∼4-fold higher levels of H3K27me3, distinct chromatin organization and compaction, and a specific transcriptional pattern. βHI and βLO cells also differ in size, morphology, cytosolic and nuclear ultrastructure, epigenomes, cell surface marker expression, and function, and can be FACS separated into CD24+ and CD24− fractions. Functionally, βHI cells have increased mitochondrial mass, activity, and insulin secretion in vivo and ex vivo. Partial loss of function indicates that H3K27me3 dosage regulates βHI/βLO ratio in vivo, suggesting that control of β cell subtype identity and ratio is at least partially uncoupled. Both subtypes are conserved in humans, with βHI cells enriched in humans with type 2 diabetes. Thus, epigenetic dosage is a novel regulator of cell subtype specification and identifies two functionally distinct β cell subtypes.

2023-02-16 | GSE224058 | GEO

Epigenetic dosage identifies two major and functionally distinct β cell subtypes [ChIP-seq]

2023-02-16 | GSE224060 | GEO

Epigenetic dosage identifies two major and functionally distinct β cell subtypes [RNA-seq]

2023-02-16 | GSE224059 | GEO

Epigenetic dosage identifies two major and functionally distinct β cell subtypes [scRNA-seq]

2023-02-16 | GSE225436 | GEO

Epigenetic dosage identifies two major and functionally distinct β cell subtypes

Project description:Epigenetic dosage identifies two major and functionally distinct β cell subtypes

| PRJNA929496 | ENA

Epigenetic dosage identifies two major and functionally distinct β cell subtypes [DNAmethArray]

Project description:Epigenetic dosage identifies two major and functionally distinct β cell subtypes [DNAmethArray]

| PRJNA929497 | ENA

Epigenetic dosage identifies two major and functionally distinct β cell subtypes [RNA-seq]

Project description:Epigenetic dosage identifies two major and functionally distinct β cell subtypes [RNA-seq]

| PRJNA929498 | ENA

Epigenetic dosage identifies two major and functionally distinct β cell subtypes [scRNA-seq]

Project description:Epigenetic dosage identifies two major and functionally distinct β cell subtypes [scRNA-seq]

| PRJNA935693 | ENA

Epigenetic dosage identifies two major and functionally distinct β cell subtypes [ChIP-seq]

Project description:Epigenetic dosage identifies two major and functionally distinct β cell subtypes [ChIP-seq]

| PRJNA929499 | ENA

Analysis of gene expression signatures identifies prognostic and functionally distinct ovarian clear cell carcinoma subtypes.

Project description:BackgroundOvarian clear cell carcinoma (OCCC) is a histological subtype of epithelial ovarian cancer (EOC) with distinct pathological, biological, and molecular features. OCCCs are more resistant to conventional treatment regimen of EOC and have the worst stage-adjusted prognosis amongst EOC subtypes. As the OCCC incidence rate in Asian populations has significantly increased in recent decades, it is critical to elucidate its molecular features that could lead to OCCC-tailored therapeutic strategies.MethodsGene expression profiles of 222 OCCC were analyzed by hierarchical clustering and statistical analyses.FindingsWe identified two OCCC gene expression subtypes: EpiCC-epithelial-like, which is associated with early-stage disease, with a relatively higher rate of gene mutations in the SWI/SNF complex; and MesCC-mesenchymal-like, associated with late-stage and higher enrichment of immune-related pathway activity. Genetic, copy number and transcriptomic analyses showed that both EpiCC and MesCC carried OCCC-associated aberrations. The EpiCC/MesCC classification was reproducible in validation cohorts and OCCC cell lines. MesCC tumors had a poorer progression-free survival (PFS) than EpiCC tumors (HR: 3·0, p = 0·0006). Functional assays in cell lines showed that the MesCC subtype was more proliferative and more anoikis-resistant than the EpiCC. By applying the EpiCC/MesCC classification to the TCGA renal clear cell carcinoma cohort, our results indicated interoperability of the subtyping scheme, and revealed preferential drug response of MesCC to bevacizumab.InterpretationThe EpiCC/MesCC classification shows promise for prognostic and therapeutic stratification in OCCC patients and warrants further investigation in the context of OCCC gene expression subtype-tailored treatment strategies.

| S-EPMC6921362 | biostudies-literature

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