Multiomic Profiling Identifies cis-Regulatory Networks Underlying Human Pancreatic ? Cell Identity and Function.

ABSTRACT: EndoC-?H1 is emerging as a critical human ? cell model to study the genetic and environmental etiologies of ? 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-?H1. Analyses of these maps define known (e.g., PDX1 and ISL1) and putative (e.g., PCSK1 and mir-375) ? 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 ? cells indicates preservation of chromatin looping but also highlights chromosomal aberrations and fetal genomic signatures in EndoC-?H1. 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 ? cell identity and (dys)function in diabetes.

SUBMITTER: Lawlor N 

PROVIDER: S-EPMC6389269 | biostudies-literature | 2019 Jan

REPOSITORIES: biostudies-literature