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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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    as
    1. David U. Gorkin & Iros Barozzi & Yuan Zhao & Yanxiao Zhang & Hui Huang & Ah Young Lee & Bin Li & Joshua Chiou & Andre Wildberg & Bo Ding & Bo Zhang & Mengchi Wang & J. Seth Strattan & Jean M. Davidson, 2020. "An atlas of dynamic chromatin landscapes in mouse fetal development," Nature, Nature, vol. 583(7818), pages 744-751, July.
    2. Yasuhiko Minokoshi & Thierry Alquier & Noboru Furukawa & Young-Bum Kim & Anna Lee & Bingzhong Xue & James Mu & Fabienne Foufelle & Pascal Ferré & Morris J. Birnbaum & Bettina J. Stuck & Barbara B. Kah, 2004. "AMP-kinase regulates food intake by responding to hormonal and nutrient signals in the hypothalamus," Nature, Nature, vol. 428(6982), pages 569-574, April.
    3. Eleanor Wheeler & Aaron Leong & Ching-Ti Liu & Marie-France Hivert & Rona J Strawbridge & Clara Podmore & Man Li & Jie Yao & Xueling Sim & Jaeyoung Hong & Audrey Y Chu & Weihua Zhang & Xu Wang & Peng , 2017. "Impact of common genetic determinants of Hemoglobin A1c on type 2 diabetes risk and diagnosis in ancestrally diverse populations: A transethnic genome-wide meta-analysis," PLOS Medicine, Public Library of Science, vol. 14(9), pages 1-30, September.
    4. Mason A. Israel & Shauna H. Yuan & Cedric Bardy & Sol M. Reyna & Yangling Mu & Cheryl Herrera & Michael P. Hefferan & Sebastiaan Van Gorp & Kristopher L. Nazor & Francesca S. Boscolo & Christian T. Ca, 2012. "Probing sporadic and familial Alzheimer’s disease using induced pluripotent stem cells," Nature, Nature, vol. 482(7384), pages 216-220, February.
    5. Jian Yan & Yunjiang Qiu & André M. Ribeiro dos Santos & Yimeng Yin & Yang E. Li & Nick Vinckier & Naoki Nariai & Paola Benaglio & Anugraha Raman & Xiaoyu Li & Shicai Fan & Joshua Chiou & Fulin Chen & , 2021. "Systematic analysis of binding of transcription factors to noncoding variants," Nature, Nature, vol. 591(7848), pages 147-151, March.
    6. Arjun Bhattacharya & Anastasia N. Freedman & Vennela Avula & Rebeca Harris & Weifang Liu & Calvin Pan & Aldons J. Lusis & Robert M. Joseph & Lisa Smeester & Hadley J. Hartwell & Karl C. K. Kuban & Car, 2022. "Placental genomics mediates genetic associations with complex health traits and disease," Nature Communications, Nature, vol. 13(1), pages 1-15, December.
    7. Jason Ernst & Pouya Kheradpour & Tarjei S. Mikkelsen & Noam Shoresh & Lucas D. Ward & Charles B. Epstein & Xiaolan Zhang & Li Wang & Robbyn Issner & Michael Coyne & Manching Ku & Timothy Durham & Mano, 2011. "Mapping and analysis of chromatin state dynamics in nine human cell types," Nature, Nature, vol. 473(7345), pages 43-49, May.
    8. Joshua Chiou & Ryan J. Geusz & Mei-Lin Okino & Jee Yun Han & Michael Miller & Rebecca Melton & Elisha Beebe & Paola Benaglio & Serina Huang & Katha Korgaonkar & Sandra Heller & Alexander Kleger & Seba, 2021. "Interpreting type 1 diabetes risk with genetics and single-cell epigenomics," Nature, Nature, vol. 594(7863), pages 398-402, June.
    9. Åsa Apelqvist & Hao Li & Lukas Sommer & Paul Beatus & David J. Anderson & Tasuku Honjo & Martin Hrabě de Angelis & Urban Lendahl & Helena Edlund, 1999. "Notch signalling controls pancreatic cell differentiation," Nature, Nature, vol. 400(6747), pages 877-881, August.
    10. David U. Gorkin & Iros Barozzi & Yuan Zhao & Yanxiao Zhang & Hui Huang & Ah Young Lee & Bin Li & Joshua Chiou & Andre Wildberg & Bo Ding & Bo Zhang & Mengchi Wang & J. Seth Strattan & Jean M. Davidson, 2020. "Author Correction: An atlas of dynamic chromatin landscapes in mouse fetal development," Nature, Nature, vol. 586(7831), pages 31-31, October.
    11. Christopher Chase Bolt & Lucille Lopez-Delisle & Aurélie Hintermann & Bénédicte Mascrez & Antonella Rauseo & Guillaume Andrey & Denis Duboule, 2022. "Context-dependent enhancer function revealed by targeted inter-TAD relocation," Nature Communications, Nature, vol. 13(1), pages 1-15, December.
    12. Sarah E. Graham & Shoa L. Clarke & Kuan-Han H. Wu & Stavroula Kanoni & Greg J. M. Zajac & Shweta Ramdas & Ida Surakka & Ioanna Ntalla & Sailaja Vedantam & Thomas W. Winkler & Adam E. Locke & Eirini Ma, 2021. "The power of genetic diversity in genome-wide association studies of lipids," Nature, Nature, vol. 600(7890), pages 675-679, December.
    13. Adrian Veres & Aubrey L. Faust & Henry L. Bushnell & Elise N. Engquist & Jennifer Hyoje-Ryu Kenty & George Harb & Yeh-Chuin Poh & Elad Sintov & Mads Gürtler & Felicia W. Pagliuca & Quinn P. Peterson &, 2019. "Charting cellular identity during human in vitro β-cell differentiation," Nature, Nature, vol. 569(7756), pages 368-373, May.
    14. Diego Garrido-Martín & Beatrice Borsari & Miquel Calvo & Ferran Reverter & Roderic Guigó, 2021. "Identification and analysis of splicing quantitative trait loci across multiple tissues in the human genome," Nature Communications, Nature, vol. 12(1), pages 1-16, December.
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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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