フジタ　キヨウヘイ   Fujita Kiyouhei   藤田　恭平    所属   医学部 医学科    職種   助教
論文種別	原著
言語種別	英語
査読の有無	査読あり
表題	eQTL mapping in fetal-like pancreatic progenitor cells reveals early developmental insights into diabetes risk.
掲載誌名	正式名：Nature communications 略　 称：Nat Commun ISSNコード：20411723/20411723
掲載区分	国外
巻・号・頁	14(1),pp.6928
著者・共著者	Nguyen Jennifer P, Arthur Timothy D, Fujita Kyohei, Salgado Bianca M, Donovan Margaret K R, , Matsui Hiroko, Kim Ji Hyun, D'Antonio-Chronowska Agnieszka, D'Antonio Matteo, Frazer Kelly A
発行年月	2023/10
概要	The impact of genetic regulatory variation active in early pancreatic development on adult pancreatic disease and traits is not well understood. Here, we generate a panel of 107 fetal-like iPSC-derived pancreatic progenitor cells (iPSC-PPCs) from whole genome-sequenced individuals and identify 4065 genes and 4016 isoforms whose expression and/or alternative splicing are affected by regulatory variation. We integrate eQTLs identified in adult islets and whole pancreas samples, which reveal 1805 eQTL associations that are unique to the fetal-like iPSC-PPCs and 1043 eQTLs that exhibit regulatory plasticity across the fetal-like and adult pancreas tissues. Colocalization with GWAS risk loci for pancreatic diseases and traits show that some putative causal regulatory variants are active only in the fetal-like iPSC-PPCs and likely influence disease by modulating expression of disease-associated genes in early development, while others with regulatory plasticity likely exert their effects in both the fetal and adult pancreas by modulating expression of different disease genes in the two developmental stages.
DOI	10.1038/s41467-023-42560-4
PMID	37903777