Haematopoietic Stem Cell Self-renewal in Vivo and Ex Vivo

Overview

Journal Nat Rev Genet

Specialty Genetics

Date 2020 May 30

PMID 32467607

Citations 98

Authors

Adam C Wilkinson

Kyomi J Igarashi

Hiromitsu Nakauchi

Affiliations

Soon will be listed here.

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.

Citing Articles

Cannabidiol restores hematopoietic stem cell stemness in mouse through Atf2-Lrp6 axis after acute irradiation.

Bai Z, Huang C, Xu H, Wang Y, Liao Z, Shen P MedComm (2020). 2025; 6(2):e70092.

PMID: 39949985 PMC: 11822450. DOI: 10.1002/mco2.70092.

Biomolecular condensates in immune cell fate.

Kodali S, Sands C, Guo L, Huang Y, Di Stefano B Nat Rev Immunol. 2025; .

PMID: 39875604 DOI: 10.1038/s41577-025-01130-z.

In vitro erythropoiesis: the emerging potential of induced pluripotent stem cells (iPSCs).

Chukwuemeka C, Ndubueze C, Kolawole A, Joseph J, Oladipo I, Ofoezie E Blood Sci. 2024; 7(1):e00215.

PMID: 39726795 PMC: 11671056. DOI: 10.1097/BS9.0000000000000215.

Enhanced engraftment of human haematopoietic stem cells via mechanical remodelling mediated by the corticotropin-releasing hormone.

Wu M, Yang H, Liu S, Jiang L, Liang T, Wang Y Nat Biomed Eng. 2024; .

PMID: 39715892 DOI: 10.1038/s41551-024-01316-1.

Inflammasomes: potential therapeutic targets in hematopoietic stem cell transplantation.

Luo J, Zhou Y, Wang M, Zhang J, Jiang E Cell Commun Signal. 2024; 22(1):596.

PMID: 39695742 PMC: 11657697. DOI: 10.1186/s12964-024-01974-3.

References

Orkin S, Zon L . Hematopoiesis: an evolving paradigm for stem cell biology. Cell. 2008; 132(4):631-44. PMC: 2628169. DOI: 10.1016/j.cell.2008.01.025. View

Gordon M, Lewis J, Marley S . Of mice and men...and elephants. Blood. 2002; 100(13):4679-80. DOI: 10.1182/blood-2002-08-2517. View

Eaves C . Hematopoietic stem cells: concepts, definitions, and the new reality. Blood. 2015; 125(17):2605-13. PMC: 4440889. DOI: 10.1182/blood-2014-12-570200. View

Weissman I, Shizuru J . The origins of the identification and isolation of hematopoietic stem cells, and their capability to induce donor-specific transplantation tolerance and treat autoimmune diseases. Blood. 2008; 112(9):3543-53. PMC: 2574516. DOI: 10.1182/blood-2008-08-078220. View

Seita J, Weissman I . Hematopoietic stem cell: self-renewal versus differentiation. Wiley Interdiscip Rev Syst Biol Med. 2010; 2(6):640-53. PMC: 2950323. DOI: 10.1002/wsbm.86. View

Copelan E . Hematopoietic stem-cell transplantation. N Engl J Med. 2006; 354(17):1813-26. DOI: 10.1056/NEJMra052638. View

Chabannon C, Kuball J, Bondanza A, Dazzi F, Pedrazzoli P, Toubert A . Hematopoietic stem cell transplantation in its 60s: A platform for cellular therapies. Sci Transl Med. 2018; 10(436). DOI: 10.1126/scitranslmed.aap9630. View

Pinho S, Frenette P . Haematopoietic stem cell activity and interactions with the niche. Nat Rev Mol Cell Biol. 2019; 20(5):303-320. PMC: 6483843. DOI: 10.1038/s41580-019-0103-9. View

Spangrude G, Heimfeld S, Weissman I . Purification and characterization of mouse hematopoietic stem cells. Science. 1988; 241(4861):58-62. DOI: 10.1126/science.2898810. View

10.

Visser J, Bauman J, Mulder A, Eliason J, de Leeuw A . Isolation of murine pluripotent hemopoietic stem cells. J Exp Med. 1984; 159(6):1576-90. PMC: 2187316. DOI: 10.1084/jem.159.6.1576. View

11.

Kiel M, Yilmaz O, Iwashita T, Yilmaz O, Terhorst C, Morrison S . SLAM family receptors distinguish hematopoietic stem and progenitor cells and reveal endothelial niches for stem cells. Cell. 2005; 121(7):1109-21. DOI: 10.1016/j.cell.2005.05.026. View

12.

Morita Y, Ema H, Nakauchi H . Heterogeneity and hierarchy within the most primitive hematopoietic stem cell compartment. J Exp Med. 2010; 207(6):1173-82. PMC: 2882827. DOI: 10.1084/jem.20091318. View

13.

Yamamoto R, Morita Y, Ooehara J, Hamanaka S, Onodera M, Rudolph K . Clonal analysis unveils self-renewing lineage-restricted progenitors generated directly from hematopoietic stem cells. Cell. 2013; 154(5):1112-1126. DOI: 10.1016/j.cell.2013.08.007. View

14.

Balazs A, Fabian A, Esmon C, Mulligan R . Endothelial protein C receptor (CD201) explicitly identifies hematopoietic stem cells in murine bone marrow. Blood. 2005; 107(6):2317-21. PMC: 1895725. DOI: 10.1182/blood-2005-06-2249. View

15.

Gazit R, Mandal P, Ebina W, Ben-Zvi A, Nombela-Arrieta C, Silberstein L . Fgd5 identifies hematopoietic stem cells in the murine bone marrow. J Exp Med. 2014; 211(7):1315-31. PMC: 4076584. DOI: 10.1084/jem.20130428. View

16.

Chen J, Miyanishi M, Wang S, Yamazaki S, Sinha R, Kao K . Hoxb5 marks long-term haematopoietic stem cells and reveals a homogenous perivascular niche. Nature. 2016; 530(7589):223-7. PMC: 4854608. DOI: 10.1038/nature16943. View

17.

Kataoka K, Sato T, Yoshimi A, Goyama S, Tsuruta T, Kobayashi H . Evi1 is essential for hematopoietic stem cell self-renewal, and its expression marks hematopoietic cells with long-term multilineage repopulating activity. J Exp Med. 2011; 208(12):2403-16. PMC: 3256960. DOI: 10.1084/jem.20110447. View

18.

Acar M, Kocherlakota K, Murphy M, Peyer J, Oguro H, Inra C . Deep imaging of bone marrow shows non-dividing stem cells are mainly perisinusoidal. Nature. 2015; 526(7571):126-30. PMC: 4850557. DOI: 10.1038/nature15250. View

19.

Tajima Y, Ito K, Umino A, Wilkinson A, Nakauchi H, Yamazaki S . Continuous cell supply from Krt7-expressing hematopoietic stem cells during native hematopoiesis revealed by targeted in vivo gene transfer method. Sci Rep. 2017; 7:40684. PMC: 5241640. DOI: 10.1038/srep40684. View

20.

Notta F, Doulatov S, Laurenti E, Poeppl A, Jurisica I, Dick J . Isolation of single human hematopoietic stem cells capable of long-term multilineage engraftment. Science. 2011; 333(6039):218-21. DOI: 10.1126/science.1201219. View