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The path from stem cells to red blood cells

  • Progress in Hematology
  • The path from stem cells to red blood cells
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Abstract

As oxygen is essential for energy production in mitochondria, a sufficient amount of oxygen should be continuously delivered to the tissues to maintain life. Therefore, the number of red blood cells which carry the oxygen is considerable, at up to 25 trillion in the body, and 2 million new red blood cells are generated per second.

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References

  1. Pop R, Shearstone JR, Shen Q, Liu Y, Hallstrom K, Koulnis M, et al. A key commitment step in erythropoiesis is synchronized with the cell cycle clock through mutual inhibition between PU.1 and S-phase progression. PLoS Biol. 2010;8(9):e1000484. https://doi.org/10.1371/journal.pbio.1000484.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Hwang Y, Futran M, Hidalgo D, Pop R, Iyer DR, Scully R, et al. Global increase in replication fork speed during a p57KIP2-regulated erythroid cell fate switch. Sci Adv. 2017;3:e1700298.

    Article  Google Scholar 

  3. Tusi BK, Wolock SL, Weinreb C, Hwang Y, Hidalgo D, Zilionis R, et al. Population snapshots predict early haematopoietic and erythroid hierarchies. Nature. 2018;555(7694):54–60.

    Article  CAS  Google Scholar 

  4. Weinreb C, Wolock S, Tusi BK, Socolovsky M, Klein AM. Fundamental limits on dynamic inference from single-cell snapshots. Proc Natl Acad Sci USA. 2018;115(10):E2467–76.

    Article  CAS  Google Scholar 

  5. Hidalgo D, Bejder J, Pop R, Gellatly K, Hwang Y, Maxwell Scalf S, et al. EpoR stimulates rapid cycling and larger red cells during mouse and human erythropoiesis. Nat Commun. 2021;12(1):7334. https://doi.org/10.1038/s41467-021-27562-4.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Chen JJ, Zhang S. Translational control by heme-regulated elF2alpha kinase during erythropoiesis. Curr Opin Hematol. 2022;29(3):103–11.

    Article  CAS  Google Scholar 

  7. Fujiwara T, Harigae H. Biology of heme in mammalian erythroid cells and related disorders. Biomed Res Int. 2015;2015: 278536. https://doi.org/10.1155/2015/278536.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Ogawa K, Sun J, Taketani S, Nakajima O, Nishitani C, Sassa S, et al. Heme mediates derepression of Maf recognition element through direct binding to transcription repressor Bach1. EMBO J. 2001;20(11):2835–43.

    Article  CAS  Google Scholar 

  9. Tahara T, Sun J, Igarashi K, Taketani S. Heme-dependent up-regulation of the alpha-globin gene expression by transcriptional repressor Bach1 in erythroid cells. Biochem Biophys Res Commun. 2004;324(1):77–85.

    Article  CAS  Google Scholar 

  10. Tahara T, Sun J, Nakanishi K, Yamamoto M, Mori H, Saito T, et al. Heme positively regulates the expression of beta-globin at the locus control region via the transcriptional factor Bach1 in erythroid cells. J Biol Chem. 2004;279(7):5480–7.

    Article  CAS  Google Scholar 

  11. Kobayashi M, Kato H, Hada H, Itoh-Nakadai A, Fujiwara T, Muto A, et al. Iron-heme-Bach1 axis is involved in erythroblast adaptation to iron deficiency. Haematologica. 2017;102(3):454–65. https://doi.org/10.3324/haematol.2016.151043.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Tanimura N, Miller E, Igarashi K, Yang D, Burstyn JN, Dewey CN, et al. Mechanism governing heme synthesis reveals a GATA factor/heme circuit that controls differentiation. EMBO Rep. 2016;17:249–65.

    Article  CAS  Google Scholar 

  13. Camaschella C. Iron-deficiency anemia. N Engl J Med. 2015;372:1832–43.

    Article  Google Scholar 

  14. Ganz T. Anemia of inflammation. N Engl J Med. 2019;381:1148–57.

    Article  CAS  Google Scholar 

  15. Fujiwara T, Harigae H. Molecular pathophysiology and genetic mutations in congenital sideroblastic anemia. Free Radic Biol Med. 2019;133:179–85. https://doi.org/10.1016/j.freeradbiomed.2018.08.008.

    Article  CAS  PubMed  Google Scholar 

  16. Nemeth E, Tuttle MS, Powelson J, Vaughn MB, Donovan A, Ward DM, et al. Hepcidin regulates cellular iron efflux by binding to ferroportin and inducing its internalization. Science. 2004;306(5704):2090–3.

    Article  CAS  Google Scholar 

  17. Kautz L, Jung G, Valore EV, Rivella S, Nemeth E, Ganz T. Identification of erythroferrone as an erythroid regulator of iron metabolism. Nat Genet. 2014;46:678–84.

    Article  CAS  Google Scholar 

  18. Ghosh MC, Zhang D-L, Jeong SY, Kovtunovych G, Ollivierre-Wilson H, Noguchi A, et al. Deletion of iron regulatory protein 1 causes polycythemia and pulmonary hypertension in mice through translational derepression of HIF2α. Cell Metab. 2013;17(2):271–81.

    Article  CAS  Google Scholar 

  19. Anderson SA, Nizzi CP, Chang Y-I, Deck KM, Schmidt PJ, Galy B, et al. The IRP1-HIF-2α axis coordinates iron and oxygen sensing with erythropoiesis and iron absorption. Cell Metab. 2013;17(2):282–90.

    Article  CAS  Google Scholar 

  20. Yoshida H, Kawane K, Koike M, Mori Y, Uchiyama Y, Nagata S. Phosphatidylserine-dependent engulfment by macrophages of nuclei from erythroid precursor cells. Nature. 2005;437:754–8.

    Article  CAS  Google Scholar 

  21. Popova EY, Krauss SW, Short SA, Lee G, Villalobos J, Etzell J, et al. Chromatin condensation in terminally differentiating mouse erythroblasts does not involve special architectural proteins but depends on histone deacetylation. Chromosome Res. 2009;17(47–64):18.

    Google Scholar 

  22. Ji P, Yeh V, Ramirez T, Murata-Hori M, Lodish HF. Histone deacetylase 2 is required for chromatin condensation and subsequent enucleation of cultured mouse fetal erythroblasts. Haematologica. 2010;95(12):2013–21.

    Article  CAS  Google Scholar 

  23. Wang Y, Li W, Schulz VP, Zhao H, Qu X, Qi Q, et al. Impairment of human terminal erythroid differentiation by histone deacetylase 5 deficiency. Blood. 2021;138(17):1615–27.

    Article  CAS  Google Scholar 

  24. Kobayashi I, Ubukawa K, Sugawara K, Asanuma K, Guo YM, Yamashita J, et al. Erythroblast enucleation is a dynein-dependent process. Exp Hematol. 2016;44:247–56.

    Article  CAS  Google Scholar 

  25. Ubukawa K, Guo YM, Takahashi M, Hirokawa M, Michishita Y, Nara M, et al. Enucleation of human erythroblasts involves non-muscle myosin IIB. Blood. 2012;119:1036–44.

    Article  CAS  Google Scholar 

  26. Ubukawa K, Goto T, Asanuma K, Sasaki Y, Guo YM, Kobayashi I, et al. Cdc42 regulates cell polarization and contractile actomyosin rings during terminal differentiation of human erythroblasts. Sci Rep. 2020;10:11806.

    Article  CAS  Google Scholar 

  27. Gnanapragasam MN, McGrath KE, Catherman S, Xue L, Palis J, Bieker JJ. EKLF/KLF1-regulated cell cycle exit is essential for erythroblast enucleation. Blood. 2016;128:1631–2164.

    Article  CAS  Google Scholar 

  28. Soboleva S, Kurita R, Ek F, Åkerstrand H, Silvério-Alves R, Olsson R, et al. Identification of potential chemical compounds enhancing generation of enucleated cells from immortalized human erythroid cell lines. Commun Biol. 2021;4:677.

    Article  CAS  Google Scholar 

  29. Soboleva S, Kurita R, Kajitani N, Åkerstrand H, Miharada K. Establishment of an immortalized human erythroid cell line sustaining differentiation potential without inducible gene expression system. Hum Cell. 2022;35:408–17.

    Article  CAS  Google Scholar 

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Authors and Affiliations

  1. Department of Hematology, Tohoku University Graduate School of Medicine, Sendai, Japan

    Hideo Harigae

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  1. Hideo Harigae
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Correspondence to Hideo Harigae.

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Harigae, H. The path from stem cells to red blood cells. Int J Hematol 116, 160–162 (2022). https://doi.org/10.1007/s12185-022-03413-w

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  • DOI: https://doi.org/10.1007/s12185-022-03413-w

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