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Lineage tracing of human embryonic development and foetal haematopoiesis through somatic mutations

By Michael Spencer Chapman, Anna Maria Ranzoni, Brynelle Myers, Nick Williams, Tim Coorens, Emily Mitchell, Timothy Butler, Kevin J. Dawson, Yvette Hooks, Luiza Moore, Jyoti Nangalia, Philip S Robinson, Elizabeth Hook, Peter J. Campbell, Ana Cvejic

Posted 30 May 2020
bioRxiv DOI: 10.1101/2020.05.29.088765

To date, ontogeny of the human haematopoietic system during foetal development has been characterized mainly through careful microscopic observations. Here we used whole-genome sequencing (WGS) of 511 single-cell derived haematopoietic colonies from healthy human foetuses of 8 and 18 post-conception weeks (pcw) coupled with deep targeted sequencing of tissues of known embryonic origin to reconstruct a phylogenetic tree of blood development. We found that in healthy foetuses, individual haematopoietic progenitors acquire tens of somatic mutations by 18 pcw. Using these mutations as barcodes, we 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 analysis has shown that ectoderm originates from a smaller set of blood antecedents compared to endoderm and mesoderm. Finally, our data support a hypoblast origin of the extra-embryonic mesoderm and primitive blood in humans. ### Competing Interest Statement The authors have declared no competing interest.

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