Kyohei Fujita    Department   Research Institutes and Facilities, Research Institutes and Facilities    Position   Assistant Professor (Fixed Term)
Article types	Original article
Language	English
Peer review	Peer reviewed
Title	eQTL mapping in fetal-like pancreatic progenitor cells reveals early developmental insights into diabetes risk.
Journal	Formal name：Nature communications Abbreviation：Nat Commun ISSN code：20411723/20411723
Domestic / Foregin	Foregin
Volume, Issue, Page	14(1),pp.6928
Author and coauthor	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
Publication date	2023/10
Summary	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