eQTL mapping in fetal-like pancreatic progenitor cells reveals early developmental insights into diabetes risk.

Autor: Nguyen JP; Bioinformatics and Systems Biology Graduate Program, University of California, San Diego, La Jolla, CA, 92093, USA.; Department of Biomedical Informatics, University of California, San Diego, La Jolla, CA, 92093, USA., Arthur TD; Department of Biomedical Informatics, University of California, San Diego, La Jolla, CA, 92093, USA.; Biomedical Sciences Graduate Program, University of California, San Diego, La Jolla, CA, 92093, USA., Fujita K; Department of Pediatrics, University of California, San Diego, La Jolla, CA, 92093, USA., Salgado BM; Institute of Genomic Medicine, University of California San Diego, 9500 Gilman Dr, La Jolla, CA, 92093, USA., Donovan MKR; Bioinformatics and Systems Biology Graduate Program, University of California, San Diego, La Jolla, CA, 92093, USA.; Department of Biomedical Informatics, University of California, San Diego, La Jolla, CA, 92093, USA., Matsui H; Institute of Genomic Medicine, University of California San Diego, 9500 Gilman Dr, La Jolla, CA, 92093, USA., Kim JH; Department of Pediatrics, Dongguk University Ilsan Hospital, Goyang, South Korea., D'Antonio-Chronowska A; Department of Pediatrics, University of California, San Diego, La Jolla, CA, 92093, USA., D'Antonio M; Department of Biomedical Informatics, University of California, San Diego, La Jolla, CA, 92093, USA.; Department of Pediatrics, University of California, San Diego, La Jolla, CA, 92093, USA.; Institute of Genomic Medicine, University of California San Diego, 9500 Gilman Dr, La Jolla, CA, 92093, USA., Frazer KA; Department of Pediatrics, University of California, San Diego, La Jolla, CA, 92093, USA. kafrazer@health.ucsd.edu.; Institute of Genomic Medicine, University of California San Diego, 9500 Gilman Dr, La Jolla, CA, 92093, USA. kafrazer@health.ucsd.edu.
Jazyk: angličtina
Zdroj: Nature communications [Nat Commun] 2023 Oct 30; Vol. 14 (1), pp. 6928. Date of Electronic Publication: 2023 Oct 30.
DOI: 10.1038/s41467-023-42560-4
Abstrakt: 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.
(© 2023. The Author(s).)
Databáze: MEDLINE
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