Cell Reports (Mar 2023)

HSC-independent definitive hematopoiesis persists into adult life

  • Michihiro Kobayashi,
  • Haichao Wei,
  • Takashi Yamanashi,
  • Nathalia Azevedo Portilho,
  • Samuel Cornelius,
  • Noemi Valiente,
  • Chika Nishida,
  • Haizi Cheng,
  • Augusto Latorre,
  • W. Jim Zheng,
  • Joonsoo Kang,
  • Jun Seita,
  • David J. Shih,
  • Jia Qian Wu,
  • Momoko Yoshimoto

Journal volume & issue
Vol. 42, no. 3
p. 112239

Abstract

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Summary: It is widely believed that hematopoiesis after birth is established by hematopoietic stem cells (HSCs) in the bone marrow and that HSC-independent hematopoiesis is limited only to primitive erythro-myeloid cells and tissue-resident innate immune cells arising in the embryo. Here, surprisingly, we find that significant percentages of lymphocytes are not derived from HSCs, even in 1-year-old mice. Instead, multiple waves of hematopoiesis occur from embryonic day 7.5 (E7.5) to E11.5 endothelial cells, which simultaneously produce HSCs and lymphoid progenitors that constitute many layers of adaptive T and B lymphocytes in adult mice. Additionally, HSC lineage tracing reveals that the contribution of fetal liver HSCs to peritoneal B-1a cells is minimal and that the majority of B-1a cells are HSC independent. Our discovery of extensive HSC-independent lymphocytes in adult mice attests to the complex blood developmental dynamics spanning the embryo-to-adult transition and challenges the paradigm of HSCs exclusively underpinning the postnatal immune system.

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