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Single-cell RNA-sequencing of differentiating iPS cells reveals dynamic genetic effects on gene expression

Author

Listed:
  • Anna S. E. Cuomo

    (European Bioinformatics Institute, Wellcome Genome Campus, CB10 1SD Hinxton)

  • Daniel D. Seaton

    (European Bioinformatics Institute, Wellcome Genome Campus, CB10 1SD Hinxton)

  • Davis J. McCarthy

    (European Bioinformatics Institute, Wellcome Genome Campus, CB10 1SD Hinxton
    St Vincent’s Institute of Medical Research)

  • Iker Martinez

    (Wellcome Genome Campus)

  • Marc Jan Bonder

    (European Bioinformatics Institute, Wellcome Genome Campus, CB10 1SD Hinxton
    Wellcome Genome Campus)

  • Jose Garcia-Bernardo

    (Wellcome Genome Campus)

  • Shradha Amatya

    (Wellcome Genome Campus)

  • Pedro Madrigal

    (Wellcome Genome Campus
    Anne McLaren Laboratory, University of Cambridge
    University of Cambridge
    University of Cambridge)

  • Abigail Isaacson

    (Wellcome Genome Campus)

  • Florian Buettner

    (European Bioinformatics Institute, Wellcome Genome Campus, CB10 1SD Hinxton)

  • Andrew Knights

    (Wellcome Genome Campus)

  • Kedar Nath Natarajan

    (Wellcome Genome Campus
    Functional Genomics and Metabolism Unit, University of Southern Denmark)

  • Ludovic Vallier

    (Wellcome Genome Campus
    Anne McLaren Laboratory, University of Cambridge
    University of Cambridge)

  • John C. Marioni

    (European Bioinformatics Institute, Wellcome Genome Campus, CB10 1SD Hinxton
    Wellcome Genome Campus
    University of Cambridge)

  • Mariya Chhatriwala

    (Wellcome Genome Campus)

  • Oliver Stegle

    (European Bioinformatics Institute, Wellcome Genome Campus, CB10 1SD Hinxton
    German Cancer Research Center (DKFZ)
    Genome Biology Unit)

Abstract

Recent developments in stem cell biology have enabled the study of cell fate decisions in early human development that are impossible to study in vivo. However, understanding how development varies across individuals and, in particular, the influence of common genetic variants during this process has not been characterised. Here, we exploit human iPS cell lines from 125 donors, a pooled experimental design, and single-cell RNA-sequencing to study population variation of endoderm differentiation. We identify molecular markers that are predictive of differentiation efficiency of individual lines, and utilise heterogeneity in the genetic background across individuals to map hundreds of expression quantitative trait loci that influence expression dynamically during differentiation and across cellular contexts.

Suggested Citation

  • Anna S. E. Cuomo & Daniel D. Seaton & Davis J. McCarthy & Iker Martinez & Marc Jan Bonder & Jose Garcia-Bernardo & Shradha Amatya & Pedro Madrigal & Abigail Isaacson & Florian Buettner & Andrew Knight, 2020. "Single-cell RNA-sequencing of differentiating iPS cells reveals dynamic genetic effects on gene expression," Nature Communications, Nature, vol. 11(1), pages 1-14, December.
    • Handle: RePEc:nat:natcom:v:11:y:2020:i:1:d:10.1038_s41467-020-14457-z
    DOI: 10.1038/s41467-020-14457-z
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