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Lifelong multilineage contribution by embryonic-born blood progenitors

Author

Listed:
  • 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
    Boston Children’s Hospital and Dana Farber Cancer Institute
    Harvard Medical School)

  • Fernando D. Camargo

    (Boston Children’s Hospital
    Harvard University)

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.

Suggested Citation

  • 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 & Fernando D. Cam, 2022. "Lifelong multilineage contribution by embryonic-born blood progenitors," Nature, Nature, vol. 606(7915), pages 747-753, June.
    • Handle: RePEc:nat:nature:v:606:y:2022:i:7915:d:10.1038_s41586-022-04804-z
    DOI: 10.1038/s41586-022-04804-z
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    Cited by:

    1. Shicheng Sun & Ali Motazedian & Jacky Y. Li & Kevin Wijanarko & Joe Jiang Zhu & Kothila Tharmarajah & Kathleen A. Strumila & Anton Shkaruta & L. Rayburn Nigos & Jacqueline V. Schiesser & Yi Yu & Paul , 2024. "Efficient generation of human NOTCH ligand-expressing haemogenic endothelial cells as infrastructure for in vitro haematopoiesis and lymphopoiesis," Nature Communications, Nature, vol. 15(1), pages 1-14, December.
    2. Roshana Thambyrajah & Maria Maqueda & Muhammad Zaki Fadlullah & Martin Proffitt & Wen Hao Neo & Yolanda Guillén & Marta Casado-Pelaez & Patricia Herrero-Molinero & Carla Brujas & Noemi Castelluccio & , 2024. "IκBα controls dormancy in hematopoietic stem cells via retinoic acid during embryonic development," Nature Communications, Nature, vol. 15(1), pages 1-17, December.

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