RT Journal Article
SR Electronic
T1 EndoC-βH1 multi-genomic profiling defines gene regulatory programs governing human pancreatic β cell identity and function
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 399139
DO 10.1101/399139
A1 Nathan Lawlor
A1 Eladio J. Márquez
A1 Peter Orchard
A1 Narisu Narisu
A1 Muhammad Saad Shamim
A1 Asa Thibodeau
A1 Arushi Varshney
A1 Romy Kursawe
A1 Michael R. Erdos
A1 Matt Kanke
A1 Huiya Gu
A1 Evgenia Pak
A1 Amalia Dutra
A1 Sheikh Russell
A1 Xingwang Li
A1 Emaly Piecuch
A1 Oscar Luo
A1 Peter S. Chines
A1 Christian Fuchbserger
A1 NIH Intramural Sequencing Center
A1 Praveen Sethupathy
A1 Aviva Presser Aiden
A1 Yijun Ruan
A1 Erez Lieberman Aiden
A1 Francis S. Collins
A1 Duygu Ucar
A1 Stephen C.J. Parker
A1 Michael L. Stitzel
YR 2018
UL http://biorxiv.org/content/early/2018/08/23/399139.abstract
AB EndoC-βH1 is emerging as a critical human beta cell model to study the genetic and environmental etiologies of beta cell function, especially in the context of diabetes. Comprehensive knowledge of its molecular landscape is lacking yet required to fully take advantage of this model. Here, we report extensive chromosomal (spectral karyotyping), genetic (genotyping), epigenetic (ChIP-seq, ATAC-seq), chromatin interaction (Hi-C, Pol2 ChIA-PET), and transcriptomic (RNA-seq, miRNA-seq) maps of this cell model. Integrated analyses of these maps define known (e.g., PDX1, ISL1) and putative (e.g., PCSK1, mir-375) beta cell-specific chromatin interactions and transcriptional cis-regulatory networks, and identify allelic effects on cis-regulatory element use and expression.Importantly, comparative analyses with maps generated in primary human islets/beta cells indicate substantial preservation of chromatin looping, but also highlight chromosomal heterogeneity and fetal genomic signatures in EndoC-βH1. Together, these maps, and an interactive web application we have created for their exploration, provide important tools for the broad community in the design and success of experiments to probe and manipulate the genetic programs governing beta cell identity and (dys)function in diabetes.