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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.
Cell reports, 01/2019, Letnik: 26, Številka: 3Journal Article
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. Display omitted •Comprehensive multiomic maps of EndoC-βH1 human β cell line and primary islets•Sequence motifs enriched in EndoC-specific enhancers reflect its precursor state•Identification of regulatory hubs preserved between EndoC-βH1 and human islets•Identified SNP alleles (including T2D GWAS) altering cis-regulatory signatures EndoC-βH1 is becoming an important cellular model to study genes and pathways governing human β cell identity and function, but its (epi)genomic similarity to primary human islets is unknown. Lawlor et al. complete and compare extensive EndoC and primary human islet multiomic maps to identify shared and distinct genomic circuitry.
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JCR | SNIP | JCR | SNIP | JCR | SNIP | JCR | SNIP |
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Vir: Osebne bibliografije
in: SICRIS
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