Lifelong multilineage contribution by embryonic-born blood progenitors

Sachin H. Patel, Constantina Christodoulou, Caleb Weinreb, Qi Yu, Edroaldo Lummertz da Rocha, Brian J. Pepe-Mooney, Sarah Bowling, Li Li, Fernando G. Osorio, George Q. Daley and Fernando D. Camargo ()
Additional contact information
Sachin H. Patel: Boston Children’s Hospital
Constantina Christodoulou: Boston Children’s Hospital
Caleb Weinreb: Harvard Medical School
Qi Yu: Boston Children’s Hospital
Edroaldo Lummertz da Rocha: Federal University of Santa Catarina
Brian J. Pepe-Mooney: Boston Children’s Hospital
Sarah Bowling: Boston Children’s Hospital
Li Li: Boston Children’s Hospital
Fernando G. Osorio: Boston Children’s Hospital
George Q. Daley: Boston Children’s Hospital
Fernando D. Camargo: Boston Children’s Hospital

Nature, 2022, vol. 606, issue 7915, 747-753

Abstract: Abstract 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.

Date: 2022
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DOI: 10.1038/s41586-022-04804-z

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