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Haematopoietic stem cell self-renewal in vivo and ex vivo

Abstract

The self-renewal capacity of multipotent haematopoietic stem cells (HSCs) supports blood system homeostasis throughout life and underlies the curative capacity of clinical HSC transplantation therapies. However, despite extensive characterization of the HSC state in the adult bone marrow and embryonic fetal liver, the mechanism of HSC self-renewal has remained elusive. This Review presents our current understanding of HSC self-renewal in vivo and ex vivo, and discusses important advances in ex vivo HSC expansion that are providing new biological insights and offering new therapeutic opportunities.

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Fig. 1: HSC self-renewal assays.
Fig. 2: Extrinsic and intrinsic factors that regulate self-renewal in embryonic and adult haematopoiesis.
Fig. 3: Components of ex vivo HSC culture systems.

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Acknowledgements

A.C.W. is supported by the Leukemia & Lymphoma Society (grant 3385-19) and the US National Institutes of Health (grant K99HL150218). K.J.I. is supported by the US National Science Foundation (grant 2018261442). H.N. is supported by the California Institute for Regenerative Medicine (grants LA1_C12-06917 and DISC1-10555), the US National Institutes of Health (grants R01DK116944, R01HL147124 and R21AG061487), JSPS KAKENHI Grant-in-Aid for Scientific Research, AMED Advanced Research and Development Programs for Medical Innovation (LEAP), and the Virginia and D.K. Ludwig Fund for Cancer Research. The article content is solely the responsibility of the authors and does not necessarily represent the official views of the US National Institutes of Health.

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H.N. declares that he is a co-founder and shareholder in ReproCELL, Megakaryon and Century Therapeutics. The other authors declare no competing interests.

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Wilkinson, A.C., Igarashi, K.J. & Nakauchi, H. Haematopoietic stem cell self-renewal in vivo and ex vivo. Nat Rev Genet 21, 541–554 (2020). https://doi.org/10.1038/s41576-020-0241-0

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