Cell Rep 2019 Jan 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.
Lawlor, Nathan; Marquez, 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 Junhong; Chines, Peter S; Fuchbserger, Christian; Center, NIH Intramural Sequencing; Sethupathy, Praveen; Aiden, Aviva Presser; Ruan, Yijun; Aiden, Erez Lieberman; Collins, Francis S; Ucar, Duygu; Parker, Stephen C J; and Stitzel, Michael L., "Multiomic Profiling Identifies cis-Regulatory Networks Underlying Human Pancreatic β Cell Identity and Function." (2019). Faculty Research 2019. 21.