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

Author

Listed:
  • Jennifer P. Nguyen

    (University of California, San Diego
    University of California, San Diego)

  • Timothy D. Arthur

    (University of California, San Diego
    University of California, San Diego)

  • Kyohei Fujita

    (University of California, San Diego)

  • Bianca M. Salgado

    (University of California San Diego, 9500 Gilman Dr)

  • Margaret K. R. Donovan

    (University of California, San Diego
    University of California, San Diego)

  • Hiroko Matsui

    (University of California San Diego, 9500 Gilman Dr)

  • Ji Hyun Kim

    (Dongguk University Ilsan Hospital)

  • Agnieszka D’Antonio-Chronowska

    (University of California, San Diego)

  • Matteo D’Antonio

    (University of California, San Diego
    University of California, San Diego
    University of California San Diego, 9500 Gilman Dr)

  • Kelly A. Frazer

    (University of California, San Diego
    University of California San Diego, 9500 Gilman Dr)

Abstract

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.

Suggested Citation

  • Jennifer P. Nguyen & Timothy D. Arthur & Kyohei Fujita & Bianca M. Salgado & Margaret K. R. Donovan & Hiroko Matsui & Ji Hyun Kim & Agnieszka D’Antonio-Chronowska & Matteo D’Antonio & Kelly A. Frazer, 2023. "eQTL mapping in fetal-like pancreatic progenitor cells reveals early developmental insights into diabetes risk," Nature Communications, Nature, vol. 14(1), pages 1-22, December.
  • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-42560-4
    DOI: 10.1038/s41467-023-42560-4
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    1. Timothy D. Arthur & Jennifer P. Nguyen & Agnieszka D’Antonio-Chronowska & Hiroko Matsui & Nayara S. Silva & Isaac N. Joshua & André D. Luchessi & William W. Young Greenwald & Matteo D’Antonio & Martin, 2024. "Complex regulatory networks influence pluripotent cell state transitions in human iPSCs," Nature Communications, Nature, vol. 15(1), pages 1-19, December.

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