Lineage tracing of human development through somatic mutations

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, Philip S. Robinson, Kenichi Yoshida, Elizabeth Hook, Peter J. Campbell () and Ana Cvejic ()
Additional contact information
Michael Spencer Chapman: Wellcome Trust Sanger Institute
Anna Maria Ranzoni: Wellcome Trust Sanger Institute
Brynelle Myers: Wellcome Trust Sanger Institute
Nicholas Williams: Wellcome Trust Sanger Institute
Tim H. H. Coorens: Wellcome Trust Sanger Institute
Emily Mitchell: Wellcome Trust Sanger 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
Jyoti Nangalia: Wellcome Trust Sanger Institute
Philip S. Robinson: Wellcome Trust Sanger Institute
Kenichi Yoshida: Wellcome Trust Sanger Institute
Elizabeth Hook: Cambridge University Hospitals NHS Foundation Trust
Peter J. Campbell: Wellcome Trust Sanger Institute
Ana Cvejic: Wellcome Trust Sanger Institute

Nature, 2021, vol. 595, issue 7865, 85-90

Abstract: 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.

Date: 2021
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DOI: 10.1038/s41586-021-03548-6

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