Regenerating haematopoiesis resembles embryonic stem cell-independent haematopoiesis

Czech version

Authors: E. Nečas; K. Faltusová ^{1,2 1}
Authors‘ workplace: Ústav patologické fyziologie, 1. lékařská fakulta, Univerzita Karlova ¹; BIOCEV, 1. lékařská fakulta, Univerzita Karlova ²
Published in: Transfuze Hematol. dnes,26, 2020, No. 3, p. 157-166.
Category: Review/Educational Papers

Overview

Tissue regeneration is a complex and highly orchestrated process leading to the reconstitution of damaged tissue and recovery of its function. Haematopoietic tissue has extensive regenerative potential which is attributed to the presence of haematopoietic stem cells. This paper briefly discusses the current understanding of haematopoietic stem cells and their participation in steady-state haematopoiesis. It also gives an overview of the three phases of embryonic and foetal haematopoiesis preceding the establishment of steady-state adult haematopoiesis. The paper presents the main conclusions drawn from our analysis of intensively regenerating bone marrow following severe damage by ionizing radiation. The research revealed a fundamental role that the developmentally advanced myeloid progenitor cells play in bone marrow regeneration, which occurs during the virtual absence of stem cells and multipotent progenitors. The regeneration induced by progenitors explains why the strong regenerative power of this tissue cannot be transplanted to other subjects with damaged haematopoiesis. A comparison of the rapidly expanding regenerating bone marrow with the expanding foetal liver haematopoiesis showed significant differences between them. However, there is a similarity between intensively regenerating haematopoiesis and embryonic definitive haematopoiesis occurring prior to the emergence of haematopoietic stem cells.

Keywords:

haematopoiesis – stem cell – progenitor cell – bone marrow – Regeneration – embryo – foetal liver

Sources

1. Dykstra B, Kent D, Bowie M, et al. Long-term propagation of distinct hematopoietic differentiation programs in vivo. Cell Stem Cell. 2007;1:218–229.

2. Six E, Guilloux A, Denis A, et al. Clonal tracking in gene therapy patients reveals a diversity of human hematopoietic differentiation programs. Blood. 2020;135:1219–1231.

3. Carrelha J, Meng Y, Kettyle LM, et al. Hierarchically related lineage- -restricted fates of multipotent haematopoietic stem cells. Nature. 2018;554:106–111.

4. Morita Y, Ema H, Nakauchi H. Heterogeneity and hierarchy within the most primitive hematopoietic stem cell compartment. J. Exp. Med. 2010;207:1173–1182.

5. Rodriguez-Fraticelli AE, Wolock SL, Weinreb CS, et al. Clonal analysis of lineage fate in native haematopoiesis. Nature. 2018;553:212– 216.

6. Clevers H, Watt FM. Defining adult stem cells by function, not by phenotype. Ann Rev Biochem. 2018;87:1015–1027.

7. Takano H, Ema H, Sudo K, Nakauchi H. Asymmetric division and lineage commitment at the level of hematopoietic stem cells: inference from differentiation in daughter cell and granddaughter cell pairs. J Exp Med. 2004;199:295–302.

8. Páral P, Faltusová K, Molík M, et al. Cell cycle and differentiation of Sca-1+ and Sca-1− hematopoietic stem and progenitor cells. Cell Cycle. 2018;17:1979–1991.

9. Brecher G, Bookstein N, Redfearn W, et al. Self-renewal of the long-term repopulating stem cell. Proc Natl Acad Sci U S A. 1993;90:6028–6031.

10. Santoro A, Vlachou T, Carminati M, et al. Molecular mechanisms of asymmetric divisions in mammary stem cells. EMBO Rep. 2016;17:1700–1720.

11. Sun J, Ramos A, Chapman B, et al. Clonal dynamics of native haematopoiesis. Nature. 2014;514:322–327.

12. Sawai CM, Babovic S, Upadhaya S, et al. Hematopoietic stem cells are the major source of multilineage hematopoiesis in adult animals. Immunity 2016;45:597–609.

13. McRae HM, Voss AK, Thomas T. Are transplantable stem cells required for adult hematopoiesis? Exp Hematol. 2019;75:1–10.

14. Ema H, Morita Y, Suda T. Heterogeneity and hierarchy of hematopoietic stem cells. Exp Hematol. 2014;42:74–82.e2.

15. Pelichovská T, Chang KT, Šefc L, et al. The late-stage foetal liver microenvironment is essential for later sensitivity of B-lymphopoiesis to suppression by oestrogens. Folia Biol (Praha). 2008;54:125–129.

16. Hlobeňová T, Šefc L, Chang K-T, et al. B-lymphopoiesis gains sensitivity to subsequent inhibition by estrogens during final phase of fetal development. Dev Comp Immunol. 2012;36:385–389.

17. McGrath KE, Frame JM, Fromm GJ, et al. A transient definitive erythroid lineage with unique regulation of the -globin locus in the mammalian embryo. Blood. 2011;117:4600–4608.

18. Palis J. Hematopoietic stem cell-independent hematopoiesis: emergence of erythroid, megakaryocyte, and myeloid potential in the mammalian embryo. FEBS Lett. 2016;590:3965–3974.

19. Dzierzak E, Bigas A. Blood development: hematopoietic stem cell dependence and independence. Cell Stem Cell. 2018;22:639–651.

20. McGrath KE, Frame JM, Fegan KH, et al. Distinct sources of hematopoietic progenitors emerge before HSCs and provide functional blood cells in the mammalian embryo. Cell Rep. 2015;11:1892–1904.

21. Gritz E, Hirschi KK. Specification and function of hemogenic endothelium during embryogenesis. Cell Mol Life Sci. 2016;73:1547–1567.

22. Rybtsov S, Ivanovs A, Zhao S, Medvinsky A. Concealed expansion of immature precursors underpins acute burst of adult HSC activity in foetal liver. Development. 2016;143:1284–1289.

23. Chang K-T, Sefc L, Psenák O, et al. Early fetal liver readily repopulates B lymphopoiesis in adult bone marrow. Stem Cells. 2005;23:230–239.

24. Copley MR, Babovic S, Benz C, et al. The Lin28b–let-7–Hmga2 axis determines the higher self-renewal potential of fetal haematopoietic stem cells. Nat Cell Biol. 2013;15:916–925.

25. Bowie MB, Kent DG, Copley MR, Eaves CJ. Steel factor responsiveness regulates the high self-renewal phenotype of fetal hematopoietic stem cells. Blood. 2007;109:5043–5048.

26. Medina KL, Kincade PW. Pregnancy-related steroids are potential negative regulators of B lymphopoiesis. Proc Natl Acad Sci U S A. 1994;91:5382–5386.

27. Forgacova K, Savvulidi F, Sefc L, et al. All hematopoietic stem cells engraft in submyeloablatively irradiated mice. Biol Blood Marrow Transplant. 2013;19:713–719.

28. McCarthy KF. Population size and radiosensitivity of murine hematopoietic endogenous long-term repopulating cells. Blood. 1997;89:834–841.

29. Faltusová K, Chen C-L, Heizer T, et al. Altered erythro-myeloid progenitor cells are highly expanded in intensively regenerating hematopoiesis. Front Cell Dev Biol. 2020;8:98.

30. Ogawa M, Matsuzaki Y, Nishikawa S, et al. Expression and function of c-kit in hemopoietic progenitor cells. J Exp Med. 1991;174:63–71.

31. Morrison SJ, Scadden DT. The bone marrow niche for haematopoietic stem cells. Nature. 2014;505:327–334.

32. Simonnet AJ, Nehmé J, Vaigot P, et al. Phenotypic and functional changes induced in hematopoietic stem/progenitor cells after gamma-ray radiation exposure. Stem Cells. 2009;27:1400–1409.

33. Peslak S a, Wenger J, Bemis JC, et al. EPO-mediated expansion of late-stage erythroid progenitors in the bone marrow initiates recovery from sublethal radiation stress. Blood. 2012;120:2501–2511.

34. Cetkovský P, Mayer J, Starý J, et al.Transplantace kostní dřeně a periferních hematopoetických buněk. Praha: Galén, 2016.

35. Lysák D, Budina M, Holubová M JP. Externí hodnocení kvality stanovení CD34+ buněk v České a Slovenské republice – dlouhodobé zkušenosti z osmiletého období. Transfuze Hematol Dnes. 2019;25:258–263.