Multiomic Profiling Identifies cis-Regulatory Networks Underlying Human Pancreatic β Cell Identity and Function
Cell Reports. 2019-01-15;26(3):788-801.e6.
- EndoC-βH1 is emerging as a critical human β cell model to study the genetic and environmental etiologies of β cell (dys)function and diabetes. Comprehensive knowledge of its molecular landscape is lacking, yet required, for effective use of this model. Here, we report chromosomal (spectral karyotyping), genetic (genotyping), epigenomic (ChIP-seq and ATAC-seq), chromatin interaction (Hi-C and Pol2 ChIA-PET), and transcriptomic (RNA-seq and miRNA-seq) maps of EndoC-βH1. Analyses of these maps define known (e.g., PDX1 and ISL1) and putative (e.g., PCSK1 and mir-375) β cell-specific transcriptional cis-regulatory networks and identify allelic effects on cis-regulatory element use. Importantly, comparison with maps generated in primary human islets and/or β cells indicates preservation of chromatin looping but also highlights chromosomal aberrations and fetal genomic signatures in EndoC-βH1. Together, these maps, and a web application we created for their exploration, provide important tools for the design of experiments to probe and manipulate the genetic programs governing β cell identity and (dys)function in diabetes.
- Consortium data used in this publication
- DSR951IJE, DSR433ZII, DSR493IUR, DSR491PCF, DSR711XYC, DSR507OYE, DSR877MKM, DSR021NCC, DSR750TJE, DSR432JKO, DSR078ZJN, DSR605JWQ, DSR981VUE, DSR950AQS, DSR686VIP, DSR532IKD, DSR265SZE, DSR986YKL, DSR373FUA, DSR871UFR