Document Type

Article

Publication Date

1-15-2019

Keywords

JGM

JAX Source

Cell Rep 2019 Jan 15; 26(3):788-801.e6

PMID

30650367

DOI

https://doi.org/10.1016/j.celrep.2018.12.083

Grant

DK092251,

Abstract

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.

Comments

We thank Jane Cha for aid in graphic design.We thank all members of the Stitzel, Ucar, Parker, Sethupathy, Collins, Ruan, and Aiden labs for helpful discussion and feedback on this study and manuscript.

This is an open access article under the CC BY-NC-ND license

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