Single-cell chromatin accessibility identifies pancreatic islet cell type- and state-specific regulatory programs of diabetes risk

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Item Type:	Article
Title:	Single-cell chromatin accessibility identifies pancreatic islet cell type- and state-specific regulatory programs of diabetes risk
Creators Name:	Chiou, J., Zeng, C., Cheng, Z., Han, J.Y., Schlichting, M., Miller, M., Mendez, R., Huang, S., Wang, J., Sui, Y., Deogaygay, A., Okino, M.L., Qiu, Y., Sun, Y., Kudtarkar, P., Fang, R., Preissl, S., Sander, M., Gorkin, D.U. and Gaulton, K.J.
Abstract:	Single-nucleus assay for transposase-accessible chromatin using sequencing (snATAC-seq) creates new opportunities to dissect cell type-specific mechanisms of complex diseases. Since pancreatic islets are central to type 2 diabetes (T2D), we profiled 15,298 islet cells by using combinatorial barcoding snATAC-seq and identified 12 clusters, including multiple alpha, beta and delta cell states. We cataloged 228,873 accessible chromatin sites and identified transcription factors underlying lineage- and state-specific regulation. We observed state-specific enrichment of fasting glucose and T2D genome-wide association studies for beta cells and enrichment for other endocrine cell types. At T2D signals localized to islet-accessible chromatin, we prioritized variants with predicted regulatory function and co-accessibility with target genes. A causal T2D variant rs231361 at the KCNQ1 locus had predicted effects on a beta cell enhancer co-accessible with INS and genome editing in embryonic stem cell-derived beta cells affected INS levels. Together our findings demonstrate the power of single-cell epigenomics for interpreting complex disease genetics.
Keywords:	Data Processing, Epigenomics, Type 2 Diabetes
Source:	Nature Genetics
ISSN:	1061-4036
Publisher:	Nature Publishing Group
Volume:	53
Number:	4
Page Range:	455-466
Date:	April 2021
Additional Information:	Copyright © The Author(s), under exclusive licence to Springer Nature America, Inc. 2021
Official Publication:	https://doi.org/10.1038/s41588-021-00823-0
External Fulltext:	View full text on PubMed Central
PubMed:	View item in PubMed

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