Decoding human fetal liver haematopoiesis.
Journal
Nature
ISSN: 1476-4687
Titre abrégé: Nature
Pays: England
ID NLM: 0410462
Informations de publication
Date de publication:
10 2019
10 2019
Historique:
received:
26
10
2018
accepted:
09
09
2019
pubmed:
11
10
2019
medline:
28
3
2020
entrez:
11
10
2019
Statut:
ppublish
Résumé
Definitive haematopoiesis in the fetal liver supports self-renewal and differentiation of haematopoietic stem cells and multipotent progenitors (HSC/MPPs) but remains poorly defined in humans. Here, using single-cell transcriptome profiling of approximately 140,000 liver and 74,000 skin, kidney and yolk sac cells, we identify the repertoire of human blood and immune cells during development. We infer differentiation trajectories from HSC/MPPs and evaluate the influence of the tissue microenvironment on blood and immune cell development. We reveal physiological erythropoiesis in fetal skin and the presence of mast cells, natural killer and innate lymphoid cell precursors in the yolk sac. We demonstrate a shift in the haemopoietic composition of fetal liver during gestation away from being predominantly erythroid, accompanied by a parallel change in differentiation potential of HSC/MPPs, which we functionally validate. Our integrated map of fetal liver haematopoiesis provides a blueprint for the study of paediatric blood and immune disorders, and a reference for harnessing the therapeutic potential of HSC/MPPs.
Identifiants
pubmed: 31597962
doi: 10.1038/s41586-019-1652-y
pii: 10.1038/s41586-019-1652-y
pmc: PMC6861135
mid: EMS84343
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
365-371Subventions
Organisme : Wellcome Trust
ID : 110104
Pays : United Kingdom
Organisme : Wellcome Trust
ID : 206194
Pays : United Kingdom
Organisme : Medical Research Council
ID : MR/R006237/1
Pays : United Kingdom
Organisme : Medical Research Council
ID : MC_PC_16040
Pays : United Kingdom
Organisme : Wellcome Trust
Pays : United Kingdom
Organisme : Medical Research Council
ID : MC_UU_00016/13
Pays : United Kingdom
Organisme : Medical Research Council
ID : MC_UU_12009/14
Pays : United Kingdom
Organisme : Medical Research Council
ID : MC_PC_12009
Pays : United Kingdom
Organisme : Wellcome Trust
ID : 107931
Pays : United Kingdom
Organisme : Wellcome Trust
ID : 211276
Pays : United Kingdom
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