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Lineage tracing of human development through somatic mutations

Author

Listed:
  • Michael Spencer Chapman

    (Wellcome Trust Sanger Institute
    Imperial College Healthcare NHS Trust
    Cambridge University Hospitals NHS Foundation Trust)

  • Anna Maria Ranzoni

    (Wellcome Trust Sanger Institute
    Wellcome Trust–Medical Research Council Cambridge Stem Cell Institute
    University of Cambridge)

  • Brynelle Myers

    (Wellcome Trust Sanger Institute
    Wellcome Trust–Medical Research Council Cambridge Stem Cell Institute
    University of Cambridge)

  • Nicholas Williams

    (Wellcome Trust Sanger Institute)

  • Tim H. H. Coorens

    (Wellcome Trust Sanger Institute)

  • Emily Mitchell

    (Wellcome Trust Sanger Institute
    Cambridge University Hospitals NHS Foundation Trust
    Wellcome Trust–Medical Research Council Cambridge Stem Cell Institute)

  • Timothy Butler

    (Wellcome Trust Sanger Institute)

  • Kevin J. Dawson

    (Wellcome Trust Sanger Institute)

  • Yvette Hooks

    (Wellcome Trust Sanger Institute)

  • Luiza Moore

    (Wellcome Trust Sanger Institute
    Cambridge University Hospitals NHS Foundation Trust)

  • Jyoti Nangalia

    (Wellcome Trust Sanger Institute
    Wellcome Trust–Medical Research Council Cambridge Stem Cell Institute
    University of Cambridge)

  • Philip S. Robinson

    (Wellcome Trust Sanger Institute
    University of Cambridge)

  • Kenichi Yoshida

    (Wellcome Trust Sanger Institute)

  • Elizabeth Hook

    (Cambridge University Hospitals NHS Foundation Trust)

  • Peter J. Campbell

    (Wellcome Trust Sanger Institute
    Wellcome Trust–Medical Research Council Cambridge Stem Cell Institute)

  • Ana Cvejic

    (Wellcome Trust Sanger Institute
    Wellcome Trust–Medical Research Council Cambridge Stem Cell Institute
    University of Cambridge)

Abstract

The ontogeny of the human haematopoietic system during fetal development has previously been characterized mainly through careful microscopic observations1. Here we reconstruct a phylogenetic tree of blood development using whole-genome sequencing of 511 single-cell-derived haematopoietic colonies from healthy human fetuses at 8 and 18 weeks after conception, coupled with deep targeted sequencing of tissues of known embryonic origin. We found that, in healthy fetuses, individual haematopoietic progenitors acquire tens of somatic mutations by 18 weeks after conception. We used these mutations as barcodes and timed the divergence of embryonic and extra-embryonic tissues during development, and estimated the number of blood antecedents at different stages of embryonic development. Our data support a hypoblast origin of the extra-embryonic mesoderm and primitive blood in humans.

Suggested Citation

  • Michael Spencer Chapman & Anna Maria Ranzoni & Brynelle Myers & Nicholas Williams & Tim H. H. Coorens & Emily Mitchell & Timothy Butler & Kevin J. Dawson & Yvette Hooks & Luiza Moore & Jyoti Nangalia , 2021. "Lineage tracing of human development through somatic mutations," Nature, Nature, vol. 595(7865), pages 85-90, July.
    • Handle: RePEc:nat:nature:v:595:y:2021:i:7865:d:10.1038_s41586-021-03548-6
    DOI: 10.1038/s41586-021-03548-6
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    Cited by:

    1. Yeongjun Jang & Livia Tomasini & Taejeong Bae & Anna Szekely & Flora M. Vaccarino & Alexej Abyzov, 2024. "Transgenerational transmission of post-zygotic mutations suggests symmetric contribution of first two blastomeres to human germline," Nature Communications, Nature, vol. 15(1), pages 1-8, December.

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