Multiomic Profiling Identifies cis-Regulatory Networks Underlying Human Pancreatic β Cell Identity and Function.
(epi)genome
EndoC-βH1
Hi-C
Pol2 ChIA-PET
genetics
human pancreatic islets
karyotype
transcriptome
type 2 diabetes
β cell
Journal
Cell reports
ISSN: 2211-1247
Titre abrégé: Cell Rep
Pays: United States
ID NLM: 101573691
Informations de publication
Date de publication:
15 01 2019
15 01 2019
Historique:
received:
07
08
2018
revised:
26
10
2018
accepted:
18
12
2018
entrez:
17
1
2019
pubmed:
17
1
2019
medline:
10
4
2020
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 30650367
pii: S2211-1247(18)32043-6
doi: 10.1016/j.celrep.2018.12.083
pmc: PMC6389269
mid: NIHMS1518857
pii:
doi:
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, N.I.H., Intramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.
Langues
eng
Sous-ensembles de citation
IM
Pagination
788-801.e6Subventions
Organisme : NHLBI NIH HHS
ID : U01 HL130010
Pays : United States
Organisme : NIDDK NIH HHS
ID : R00 DK092251
Pays : United States
Organisme : NIDDK NIH HHS
ID : R00 DK099240
Pays : United States
Organisme : Intramural NIH HHS
ID : ZIA HG000024
Pays : United States
Organisme : NHGRI NIH HHS
ID : UM1 HG009375
Pays : United States
Organisme : NHGRI NIH HHS
ID : T32 HG000040
Pays : United States
Organisme : NIH HHS
ID : DP2 OD008540
Pays : United States
Organisme : Intramural NIH HHS
ID : ZIA HG000024-24
Pays : United States
Organisme : NIDDK NIH HHS
ID : R01 DK117960
Pays : United States
Informations de copyright
Copyright © 2018 The Author(s). Published by Elsevier Inc. All rights reserved.
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