Lifelong multilineage contribution by embryonic-born blood progenitors

Haematopoietic stem cells (HSCs) arise in the embryo from the arterial endothelium through a process known as the endothelial-to-haematopoietic transition (EHT) 1 – 4 . This process generates hundreds of blood progenitors, of which a fraction go on to become definitive HSCs. It is generally thought...

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Bibliographic Details
Published in:Nature (London) 2022-06, Vol.606 (7915), p.747-753
Main Authors: Patel, Sachin H., Christodoulou, Constantina, Weinreb, Caleb, Yu, Qi, da Rocha, Edroaldo Lummertz, Pepe-Mooney, Brian J., Bowling, Sarah, Li, Li, Osorio, Fernando G., Daley, George Q., Camargo, Fernando D.
Format: Article
Language:English
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Artificial chromosomes
Blood
Bone marrow
Cell fate
Cloning
Embryos
Endothelium
Fate maps
Granulocytes
Hematopoietic stem cells
Hemopoiesis
Heterogeneity
Humanities and Social Sciences
Kinases
Labeling
Liver
multidisciplinary
Progenitor cells
Science
Science (multidisciplinary)
Stem cell transplantation
Stem cells
Young adults
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Summary:Haematopoietic stem cells (HSCs) arise in the embryo from the arterial endothelium through a process known as the endothelial-to-haematopoietic transition (EHT) 1 – 4 . This process generates hundreds of blood progenitors, of which a fraction go on to become definitive HSCs. It is generally thought that most adult blood is derived from those HSCs, but to what extent other progenitors contribute to adult haematopoiesis is not known. Here we use in situ barcoding and classical fate mapping to assess the developmental and clonal origins of adult blood in mice. Our analysis uncovers an early wave of progenitor specification—independent of traditional HSCs—that begins soon after EHT. These embryonic multipotent progenitors (eMPPs) predominantly drive haematopoiesis in the young adult, have a decreasing yet lifelong contribution over time and are the predominant source of lymphoid output. Putative eMPPs are specified within intra-arterial haematopoietic clusters and represent one fate of the earliest haematopoietic progenitors. Altogether, our results reveal functional heterogeneity during the definitive wave that leads to distinct sources of adult blood. In situ barcoding and fate mapping in mice reveals that an early wave of progenitor specification, driven by embryonic multipotent progenitor cells, gives rise to adult blood independently of haematopoietic stem cells.
ISSN:0028-0836
1476-4687
DOI:10.1038/s41586-022-04804-z