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Spencer Chapman, Michael; Ranzoni, Anna Maria; Myers, Brynelle; Williams, Nicholas; Coorens, Tim H H; Mitchell, Emily; Butler, Timothy; Dawson, Kevin J; Hooks, Yvette; Moore, Luiza; Nangalia, Jyoti; Robinson, Philip S; Yoshida, Kenichi; Hook, Elizabeth; Campbell, Peter J; Cvejic, Ana
Nature (London), 07/2021, Letnik: 595, Številka: 7865Journal Article
The ontogeny of the human haematopoietic system during fetal development has previously been characterized mainly through careful microscopic observations . 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.
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