Extensive phylogenies of human development inferred from somatic mutations.

Autor: Coorens THH; Wellcome Sanger Institute, Hinxton, UK., Moore L; Wellcome Sanger Institute, Hinxton, UK.; Department of Pathology, University of Cambridge, Cambridge, UK., Robinson PS; Wellcome Sanger Institute, Hinxton, UK.; Department of Paediatrics, University of Cambridge, Cambridge, UK., Sanghvi R; Wellcome Sanger Institute, Hinxton, UK., Christopher J; Wellcome Sanger Institute, Hinxton, UK.; Department of Paediatrics, University of Cambridge, Cambridge, UK.; Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK., Hewinson J; Wellcome Sanger Institute, Hinxton, UK., Przybilla MJ; Wellcome Sanger Institute, Hinxton, UK., Lawson ARJ; Wellcome Sanger Institute, Hinxton, UK., Spencer Chapman M; Wellcome Sanger Institute, Hinxton, UK.; Department of Haematology, Hammersmith Hospital, Imperial College Healthcare NHS Trust, London, UK.; Department of Haematology, University of Cambridge, Cambridge, UK., Cagan A; Wellcome Sanger Institute, Hinxton, UK., Oliver TRW; Wellcome Sanger Institute, Hinxton, UK.; Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK., Neville MDC; Wellcome Sanger Institute, Hinxton, UK., Hooks Y; Wellcome Sanger Institute, Hinxton, UK., Noorani A; Wellcome Sanger Institute, Hinxton, UK., Mitchell TJ; Wellcome Sanger Institute, Hinxton, UK.; Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK.; Department of Surgery, University of Cambridge, Cambridge, UK., Fitzgerald RC; MRC Cancer Unit, University of Cambridge, Biomedical Campus, Cambridge, UK., Campbell PJ; Wellcome Sanger Institute, Hinxton, UK., Martincorena I; Wellcome Sanger Institute, Hinxton, UK., Rahbari R; Wellcome Sanger Institute, Hinxton, UK., Stratton MR; Wellcome Sanger Institute, Hinxton, UK. mrs@sanger.ac.uk.
Jazyk: angličtina
Zdroj: Nature [Nature] 2021 Sep; Vol. 597 (7876), pp. 387-392. Date of Electronic Publication: 2021 Aug 25.
DOI: 10.1038/s41586-021-03790-y
Abstrakt: Starting from the zygote, all cells in the human body continuously acquire mutations. Mutations shared between different cells imply a common progenitor and are thus naturally occurring markers for lineage tracing 1,2 . Here we reconstruct extensive phylogenies of normal tissues from three adult individuals using whole-genome sequencing of 511 laser capture microdissections. Reconstructed embryonic progenitors in the same generation of a phylogeny often contribute to different extents to the adult body. The degree of this asymmetry varies between individuals, with ratios between the two reconstructed daughter cells of the zygote ranging from 60:40 to 93:7. Asymmetries pervade subsequent generations and can differ between tissues in the same individual. The phylogenies resolve the spatial embryonic patterning of tissues, revealing contiguous patches of, on average, 301 crypts in the adult colonic epithelium derived from a most recent embryonic cell and also a spatial effect in brain development. Using data from ten additional men, we investigated the developmental split between soma and germline, with results suggesting an extraembryonic contribution to primordial germ cells. This research demonstrates that, despite reaching the same ultimate tissue patterns, early bottlenecks and lineage commitments lead to substantial variation in embryonic patterns both within and between individuals.
(© 2021. The Author(s), under exclusive licence to Springer Nature Limited.)
Databáze: MEDLINE
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