Author:
Lawlor Nathan,Márquez Eladio J.,Orchard Peter,Narisu Narisu,Shamim Muhammad Saad,Thibodeau Asa,Varshney Arushi,Kursawe Romy,Erdos Michael R.,Kanke Matt,Gu Huiya,Pak Evgenia,Dutra Amalia,Russell Sheikh,Li Xingwang,Piecuch Emaly,Luo Oscar,Chines Peter S.,Fuchbserger Christian,Sethupathy Praveen,Aiden Aviva Presser,Ruan Yijun,Aiden Erez Lieberman,Collins Francis S.,Ucar Duygu,Parker Stephen C.J.,Stitzel Michael L.,
Abstract
SUMMARYEndoC-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 transcriptionalcis-regulatory networks, and identify allelic effects oncis-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.
Publisher
Cold Spring Harbor Laboratory
Cited by
1 articles.
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