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
Affiliations
Michihiro Kobayashi
Center for Stem Cell and Regenerative Medicine, Brown Institute of Molecular Medicine, McGovern Medical School, University of Texas Health Science Center at Houston, Houston, TX 77030, USA
Haichao Wei
Center for Stem Cell and Regenerative Medicine, Brown Institute of Molecular Medicine, McGovern Medical School, University of Texas Health Science Center at Houston, Houston, TX 77030, USA; The Vivian L. Smith Department of Neurosurgery, McGovern Medical School, University of Texas Health Science Center at Houston, Houston, TX 77030, USA
Takashi Yamanashi
Advanced Data Science Project, RIKEN Information R&D and Strategy Headquarters, Tokyo 103-0027, Japan; Center for Integrative Medical Sciences, RIKEN, Yokohama, Kanagawa 230-0045, Japan
Nathalia Azevedo Portilho
Center for Stem Cell and Regenerative Medicine, Brown Institute of Molecular Medicine, McGovern Medical School, University of Texas Health Science Center at Houston, Houston, TX 77030, USA
Samuel Cornelius
Center for Stem Cell and Regenerative Medicine, Brown Institute of Molecular Medicine, McGovern Medical School, University of Texas Health Science Center at Houston, Houston, TX 77030, USA
Noemi Valiente
Center for Stem Cell and Regenerative Medicine, Brown Institute of Molecular Medicine, McGovern Medical School, University of Texas Health Science Center at Houston, Houston, TX 77030, USA
Chika Nishida
Center for Stem Cell and Regenerative Medicine, Brown Institute of Molecular Medicine, McGovern Medical School, University of Texas Health Science Center at Houston, Houston, TX 77030, USA
Haizi Cheng
Center for Stem Cell and Regenerative Medicine, Brown Institute of Molecular Medicine, McGovern Medical School, University of Texas Health Science Center at Houston, Houston, TX 77030, USA
Augusto Latorre
Center for Stem Cell and Regenerative Medicine, Brown Institute of Molecular Medicine, McGovern Medical School, University of Texas Health Science Center at Houston, Houston, TX 77030, USA
W. Jim Zheng
School of Biomedical Informatics, University of Texas Health Science Center at Houston, Houston, TX 77030, USA
Joonsoo Kang
Department of Pathology, University of Massachusetts Chan Medical School, Worcester, MA 01655, USA
Jun Seita
Advanced Data Science Project, RIKEN Information R&D and Strategy Headquarters, Tokyo 103-0027, Japan; Center for Integrative Medical Sciences, RIKEN, Yokohama, Kanagawa 230-0045, Japan
David J. Shih
School of Biomedical Informatics, University of Texas Health Science Center at Houston, Houston, TX 77030, USA; School of Biomedical Sciences, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong SAR, China
Jia Qian Wu
Center for Stem Cell and Regenerative Medicine, Brown Institute of Molecular Medicine, McGovern Medical School, University of Texas Health Science Center at Houston, Houston, TX 77030, USA; The Vivian L. Smith Department of Neurosurgery, McGovern Medical School, University of Texas Health Science Center at Houston, Houston, TX 77030, USA; MD Anderson Cancer Center UTHealth Graduate School of Biomedical Sciences, The University of Texas Health Science Center at Houston, Houston, TX 77030, USA
Momoko Yoshimoto
Center for Stem Cell and Regenerative Medicine, Brown Institute of Molecular Medicine, McGovern Medical School, University of Texas Health Science Center at Houston, Houston, TX 77030, USA; Corresponding author
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.
