HSC-independent definitive hematopoiesis persists into adult life
Michihiro Kobayashi, Haichao Wei, Takashi Yamanashi, Nathália Azevedo Portilho, Samuel Cornelius, Noemi Valiente, Chika Nishida, Haizi Cheng, Augusto Latorre, Wenjin Zheng, Joonsoo Kang, Jun Seita, David Shih, Jia Qian Wu, Momoko Yoshimoto
Abstract
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.