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

doi:10.1016/j.celrep.2023.112239

HSC-independent definitive hematopoiesis persists into adult life

Cell Rep. 2023 Mar 28;42(3):112239. doi: 10.1016/j.celrep.2023.112239. Epub 2023 Mar 11.

Authors

Affiliations

¹ 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.
² 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.
³ 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.
⁴ School of Biomedical Informatics, University of Texas Health Science Center at Houston, Houston, TX 77030, USA.
⁵ Department of Pathology, University of Massachusetts Chan Medical School, Worcester, MA 01655, USA.
⁶ 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.
⁷ 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.
⁸ 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. Electronic address: momoko.yoshimoto@uth.tmc.edu.

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.

Keywords: AGM region; B-1a cells; CP: Developmental biology; HSC precursors; HSC-independent hematopoiesis; adaptive immune lymphocytes; hemogenic endothelial cells; lineage tracing mouse models; mouse embryo; multi-potent progenitors.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Animals
Bone Marrow
Cell Lineage
Endothelial Cells*
Hematopoiesis
Hematopoietic Stem Cells*
Mice

Abstract

Publication types

MeSH terms

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