The Polycomb-dependent epigenome controls β-cell dysfunction, dedifferentiation and diabetes
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA434190 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR6728220_1.fastq.gz | Fastqsanger.gz | |||
| SRR6728220_2.fastq.gz | Fastqsanger.gz | |||
| SRR6728230_1.fastq.gz | Fastqsanger.gz | |||
| SRR6728230_2.fastq.gz | Fastqsanger.gz | |||
| SRR6728240_1.fastq.gz | Fastqsanger.gz |
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Project description:To date, it remains largely unclear to what extent chromatin machinery contributes to the susceptibility and progression of complex diseases. Here, we combine deep epigenome mapping with single-cell transcriptomics to mine for evidence of chromatin dysregulation in type 2 diabetes. We find two chromatin-state signatures that track β cell dysfunction in mice and humans: ectopic activation of bivalent Polycomb-silenced domains and loss of expression at an epigenomically unique class of lineage-defining genes. β cell-specific Polycomb (Eed/PRC2) loss of function in mice triggers diabetes-mimicking transcriptional signatures and highly penetrant, hyperglycemia-independent dedifferentiation, indicating that PRC2 dysregulation contributes to disease. The work provides novel resources for exploring β cell transcriptional regulation and identifies PRC2 as necessary for long-term maintenance of β cell identity. Importantly, the data suggest a two-hit (chromatin and hyperglycemia) model for loss of β cell identity in diabetes.
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