Current Stem Cell Reports

, Volume 4, Issue 4, pp 282–290 | Cite as

Extrinsic Regulation of Hematopoietic Stem Cells and Lymphocytes by Vitamin A

  • Chacko Joseph
  • Alanna C. Green
  • Diannita Kwang
  • Louise E. PurtonEmail author
In Vitro and In Vivo Models in Stem Cell Biology (E Scott, Section Editor)
Part of the following topical collections:
  1. Topical Collection on In Vitro and In Vivo Models in Stem Cell Biology


Purpose of Review

Vitamin A and its receptors, retinoic acid receptors (RARs), are key regulators of hematopoiesis. This review focuses on the extrinsic regulation of hematopoiesis by retinoids, predominantly focusing on studies in mice, but also highlighting some of the studies performed using human hematopoietic stem cells (HSCs).

Recent Findings

RARγ has key roles in regulating B and T lymphocytes via distinct bone marrow mesenchymal cells and thymic microenvironment cells, respectively. The hematopoietic phenotypes caused by vitamin A deficiency are largely due to microenvironment-induced phenotypes that occur due to RARγ deficiency. Studies using human HSCs have also revealed that the biologically active form of vitamin A increases the HSC-support potential of immature mesenchymal cell lines.


Distinct roles have been revealed for different vitamin A receptors in regulating hematopoiesis. Further elucidation of the mechanisms whereby the RARs extrinsically regulate immune cells and HSCs may provide insights leading to the development of improved therapeutics to manipulate the numbers of these cells in normal and diseased states.


Retinoids Retinoic acid receptors Bone marrow microenvironment cells Hematopoietic stem cells Lymphocytes 


Funding Information

This review was supported in part by grants from the National Health and Medical Research Council of Australia (1127551 to LEP) and the Victorian State Government Operational Infrastructure Support Program (to St. Vincent’s Institute of Medical Research).

Compliance with Ethical Standards

Conflict of Interest

Chacko Joseph, Alanna C. Green, Diannita Kwang, and Louise E Purton declare that they have no conflict of interest.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors.


Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. 1.
    Niederreither K, Dolle P. Retinoic acid in development: towards an integrated view. Nat Rev Genet. 2008;9(7):541–53.CrossRefGoogle Scholar
  2. 2.
    Chambon P. A decade of molecular biology of retinoic acid receptors. FASEB J. 1996;10(9):940–54.CrossRefGoogle Scholar
  3. 3.
    Lefebvre P, Martin PJ, Flajollet S, Dedieu S, Billaut X, Lefebvre B. Transcriptional activities of retinoic acid receptors. Vitam Horm. 2005;70:199–264.CrossRefGoogle Scholar
  4. 4.
    Huang D, Chen SW, Langston AW, Gudas LJ. A conserved retinoic acid responsive element in the murine Hoxb-1 gene is required for expression in the developing gut. Development. 1998;125(16):3235–46.PubMedGoogle Scholar
  5. 5.
    Vasios GW, Gold JD, Petkovich M, Chambon P, Gudas LJ. A retinoic acid-responsive element is present in the 5′ flanking region of the laminin B1 gene. Proc Natl Acad Sci U S A. 1989;86(23):9099–103.CrossRefGoogle Scholar
  6. 6.
    Perissi V, Jepsen K, Glass CK, Rosenfeld MG. Deconstructing repression: evolving models of co-repressor action. Nat Rev Genet. 2010;11(2):109–23.CrossRefGoogle Scholar
  7. 7.
    O’Malley BW, Kumar R. Nuclear receptor coregulators in cancer biology. Cancer Res. 2009;69(21):8217–22.CrossRefGoogle Scholar
  8. 8.
    Germain P, Chambon P, Eichele G, Evans RM, Lazar MA, Leid M, et al. International Union of Pharmacology. LX. Retinoic acid receptors. Pharmacol Rev. 2006;58(4):712–25.CrossRefGoogle Scholar
  9. 9.
    •• Grace CS, Mikkola HKA, Dou DR, Calvanese V, Ronn RE, Purton LE. Protagonist or antagonist? The complex roles of retinoids in the regulation of hematopoietic stem cells and their specification from pluripotent stem cells. Exp Hematol. 2018;65:1–16. Thoroughly reviews the roles of retinoids in regulating the self-renewal of HSCs and their specification from pluripotent stem cells. CrossRefGoogle Scholar
  10. 10.
    •• Joseph C, Nota C, Fletcher JL, Maluenda AC, Green AC, Purton LE. Retinoic acid receptor γ regulates B and T lymphopoiesis via nestin-expressing cells in the bone marrow and thymic microenvironments. J Immunol. 2016;196:2132–44. Reveals that RARγ extrinsically regulates the production of B and T lymphocytes via nestin-expressing microenvironment cells. CrossRefGoogle Scholar
  11. 11.
    Stephensen CB. Vitamin A, infection, and immune function. Annu Rev Nutr. 2001;21:167–92.CrossRefGoogle Scholar
  12. 12.
    Collins MD, Mao GE. Teratology of retinoids. Annu Rev Pharmacol Toxicol. 1999;39:399–430.CrossRefGoogle Scholar
  13. 13.
    Calis JC, Phiri KS, Faragher EB, Brabin BJ, Bates I, Cuevas LE, et al. Severe anemia in Malawian children. N Engl J Med. 2008;358(9):888–99.CrossRefGoogle Scholar
  14. 14.
    Harika R, Faber M, Samuel F, Kimiywe J, Mulugeta A, Eilander A. Micronutrient status and dietary intake of iron, vitamin A, iodine, folate and zinc in women of reproductive age and pregnant women in Ethiopia, Kenya, Nigeria and South Africa: a systematic review of data from 2005 to 2015. Nutrients. 2017;9(10).CrossRefGoogle Scholar
  15. 15.
    Humphrey JH, Agoestina T, Wu L, Usman A, Nurachim M, Subardja D, et al. Impact of neonatal vitamin A supplementation on infant morbidity and mortality. J Pediatr. 1996;128(4):489–96.CrossRefGoogle Scholar
  16. 16.
    •• Brown CC, Noelle RJ. Seeing through the dark: new insights into the immune regulatory functions of vitamin A. Eur J Immunol. 2015;45(5):1287–95. A review on the regulation of CD4+ T lymphocytes by retinoic acid. CrossRefGoogle Scholar
  17. 17.
    Rubin LP, Ross AC, Stephensen CB, Bohn T, Tanumihardjo SA. Metabolic effects of inflammation on vitamin A and carotenoids in humans and animal models. Adv Nutr. 2017;8(2):197–212.CrossRefGoogle Scholar
  18. 18.
    Hussey GD, Klein M. A randomized, controlled trial of vitamin A in children with severe measles. N Engl J Med. 1990;323(3):160–4.CrossRefGoogle Scholar
  19. 19.
    Villamor E, Mbise R, Spiegelman D, Hertzmark E, Fataki M, Peterson KE, et al. Vitamin A supplements ameliorate the adverse effect of HIV-1, malaria, and diarrheal infections on child growth. Pediatrics. 2002;109(1):E6.CrossRefGoogle Scholar
  20. 20.
    Coutsoudis A, Kiepiela P, Coovadia HM, Broughton M. Vitamin A supplementation enhances specific IgG antibody levels and total lymphocyte numbers while improving morbidity in measles. Pediatr Infect Dis J. 1992;11(3):203–9.CrossRefGoogle Scholar
  21. 21.
    Degos L, Wang ZY. All trans retinoic acid in acute promyelocytic leukemia. Oncogene. 2001;20(49):7140–5.CrossRefGoogle Scholar
  22. 22.
    Coombs CC, Tavakkoli M, Tallman MS. Acute promyelocytic leukemia: where did we start, where are we now, and the future. Blood Cancer J. 2015;5:e304.CrossRefGoogle Scholar
  23. 23.
    Huang ME, Ye YC, Chen SR, Chai JR, Lu JX, Zhoa L, et al. Use of all-trans retinoic acid in the treatment of acute promyelocytic leukemia. Blood. 1988;72(2):567–72.PubMedGoogle Scholar
  24. 24.
    Purton LE, Bernstein ID, Collins SJ. All-trans retinoic acid enhances the long-term repopulating activity of cultured hematopoietic stem cells. Blood. 2000;95(2):470–7.PubMedGoogle Scholar
  25. 25.
    Purton LE, Bernstein ID, Collins SJ. All-trans retinoic acid delays the differentiation of primitive hematopoietic precursors (lin-c-kit+Sca-1(+)) while enhancing the terminal maturation of committed granulocyte/monocyte progenitors. Blood. 1999;94(2):483–95.PubMedGoogle Scholar
  26. 26.
    Kuwata T, Wang IM, Tamura T, Ponnamperuma RM, Levine R, Holmes KL, et al. Vitamin A deficiency in mice causes a systemic expansion of myeloid cells. Blood. 2000;95(11):3349–56.PubMedGoogle Scholar
  27. 27.
    Walkley CR, Yuan YD, Chandraratna RA, McArthur GA. Retinoic acid receptor antagonism in vivo expands the numbers of precursor cells during granulopoiesis. Leukemia. 2002;16(9):1763–72.CrossRefGoogle Scholar
  28. 28.
    Lufkin T, Lohnes D, Mark M, Dierich A, Gorry P, Gaub MP, et al. High postnatal lethality and testis degeneration in retinoic acid receptor alpha mutant mice. Proc Natl Acad Sci U S A. 1993;90(15):7225–9.CrossRefGoogle Scholar
  29. 29.
    Purton LE, Dworkin S, Olsen GH, Walkley CR, Fabb SA, Collins SJ, et al. RARgamma is critical for maintaining a balance between hematopoietic stem cell self-renewal and differentiation. J Exp Med. 2006;203(5):1283–93.CrossRefGoogle Scholar
  30. 30.
    Kastner P, Chan S. Function of RARalpha during the maturation of neutrophils. Oncogene. 2001;20(49):7178–85.CrossRefGoogle Scholar
  31. 31.
    Luo J, Pasceri P, Conlon RA, Rossant J, Giguere V. Mice lacking all isoforms of retinoic acid receptor beta develop normally and are susceptible to the teratogenic effects of retinoic acid. Mech Dev. 1995;53(1):61–71.CrossRefGoogle Scholar
  32. 32.
    Lohnes D, Kastner P, Dierich A, Mark M, LeMeur M, Chambon P. Function of retinoic acid receptor gamma in the mouse. Cell. 1993;73(4):643–58.CrossRefGoogle Scholar
  33. 33.
    Walkley CR, Olsen GH, Dworkin S, Fabb SA, Swann J, McArthur GA, et al. A microenvironment-induced myeloproliferative syndrome caused by retinoic acid receptor gamma deficiency. Cell. 2007;129(6):1097–110.CrossRefGoogle Scholar
  34. 34.
    Dewamitta SR, Joseph C, Purton LE, Walkley CR. Erythroid-extrinsic regulation of normal erythropoiesis by retinoic acid receptors. Br J Haematol. 2014;164(2):280–5.CrossRefGoogle Scholar
  35. 35.
    •• Gao X, Xu C, Asada N, Frenette PS. The hematopoietic stem cell niche: from embryo to adult. Development. 2018;145(2):dev139691. Excellent review of hematopoietic stem cell niches. CrossRefGoogle Scholar
  36. 36.
    Dexter TM, Allen TD, Lajtha LG. Conditions controlling the proliferation of haemopoietic stem cells in vitro. J Cell Physiol. 1977;91(3):335–44.CrossRefGoogle Scholar
  37. 37.
    Dexter TM, Allen TD, Lajtha LG, Schofield R, Lord BI. Stimulation of differentiation and proliferation of haemopoietic cells in vitro. J Cell Physiol. 1973;82(3):461–73.CrossRefGoogle Scholar
  38. 38.
    • Joseph C, Quach JM, Walkley CR, Lane SW, Lo Celso C, Purton LE. Deciphering hematopoietic stem cells in their niches: a critical appraisal of genetic models, lineage tracing, and imaging strategies. Cell Stem Cell. 2013;13(5):520–33. Discusses different transgenic mouse models and imaging methods used to study HSC niches. CrossRefGoogle Scholar
  39. 39.
    Boulais PE, Frenette PS. Making sense of hematopoietic stem cell niches. Blood. 2015;125(17):2621–9.CrossRefGoogle Scholar
  40. 40.
    •• Kusumbe AP, Ramasamy SK, Itkin T, Mae MA, Langen UH, Betsholtz C, et al. Age-dependent modulation of vascular niches for haematopoietic stem cells. Nature. 2016;532(7599):380–4. Identifies distinct endothelial cells in bone marrow and reveals age-dependent roles in the regulation of HSCs by the vascular niche. CrossRefGoogle Scholar
  41. 41.
    •• Greenbaum A, Hsu YM, Day RB, Schuettpelz LG, Christopher MJ, Borgerding JN, et al. CXCL12 in early mesenchymal progenitors is required for haematopoietic stem-cell maintenance. Nature. 2013;495(7440):227–30. Reveals that CXCL12 produced by distinct microenvironment cells has different roles in regulating HSCs. CrossRefGoogle Scholar
  42. 42.
    Mendez-Ferrer S, Michurina TV, Ferraro F, Mazloom AR, Macarthur BD, Lira SA, et al. Mesenchymal and haematopoietic stem cells form a unique bone marrow niche. Nature. 2010;466(7308):829–34.CrossRefGoogle Scholar
  43. 43.
    •• Ding L, Morrison SJ. Haematopoietic stem cells and early lymphoid progenitors occupy distinct bone marrow niches. Nature. 2013;495(7440):231–5. Reveals distinct CXCL12-expressing niches for HSCs and lymphoid progenitors. CrossRefGoogle Scholar
  44. 44.
    Ding L, Saunders TL, Enikolopov G, Morrison SJ. Endothelial and perivascular cells maintain haematopoietic stem cells. Nature. 2012;481(7382):457–62.CrossRefGoogle Scholar
  45. 45.
    Calvi LM, Adams GB, Weibrecht KW, Weber JM, Olson DP, Knight MC, et al. Osteoblastic cells regulate the haematopoietic stem cell niche. Nature. 2003;425(6960):841–6.CrossRefGoogle Scholar
  46. 46.
    Zhang J, Niu C, Ye L, Huang H, He X, Tong WG, et al. Identification of the haematopoietic stem cell niche and control of the niche size. Nature. 2003;425(6960):836–41.CrossRefGoogle Scholar
  47. 47.
    Sugiyama T, Kohara H, Noda M, Nagasawa T. Maintenance of the hematopoietic stem cell pool by CXCL12-CXCR4 chemokine signaling in bone marrow stromal cell niches. Immunity. 2006;25(6):977–88.CrossRefGoogle Scholar
  48. 48.
    Omatsu Y, Sugiyama T, Kohara H, Kondoh G, Fujii N, Kohno K, et al. The essential functions of adipo-osteogenic progenitors as the hematopoietic stem and progenitor cell niche. Immunity. 2010;33(3):387–99.CrossRefGoogle Scholar
  49. 49.
    •• Zhou BO, Yu H, Yue R, Zhao Z, Rios JJ, Naveiras O, et al. Bone marrow adipocytes promote the regeneration of stem cells and haematopoiesis by secreting SCF. Nat Cell Biol. 2017;19(8):891–903. Shows that adipocytes are a major source of SCF and are essential in regeneration of bone marrow after injury. CrossRefGoogle Scholar
  50. 50.
    •• Crane GM, Jeffery E, Morrison SJ. Adult haematopoietic stem cell niches. Nat Rev Immunol. 2017;17(9):573–90. Excellent review of hematopoietic stem cell niches. CrossRefGoogle Scholar
  51. 51.
    •• Green AC, Rudolph-Stringer V, Chantry AD, Wu JY, Purton LE. Mesenchymal lineage cells and their importance in B lymphocyte niches. Bone 2018; in press. A thorough review of the roles of mesenchymal cell lineages in the regulation of B lymphopoiesis. Google Scholar
  52. 52.
    • Green AC, Martin TJ, Purton LE. The role of vitamin A and retinoic acid receptor signaling in post-natal maintenance of bone. J Steroid Biochem Mol Biol. 2016;155(Pt A):135–46. An extensive review of the roles of retinoids in regulating bone. CrossRefGoogle Scholar
  53. 53.
    Green AC, Poulton IJ, Vrahnas C, Hausler KD, Walkley CR, Wu JY, et al. RARgamma is a negative regulator of osteoclastogenesis. J Steroid Biochem Mol Biol. 2015;150:46–53.CrossRefGoogle Scholar
  54. 54.
    Green AC, Kocovski P, Jovic T, Walia MK, Chandraratna RAS, Martin TJ, et al. Retinoic acid receptor signalling directly regulates osteoblast and adipocyte differentiation from mesenchymal progenitor cells. Exp Cell Res. 2017;350(1):284–97.CrossRefGoogle Scholar
  55. 55.
    Kuhn R, Schwenk F, Aguet M, Rajewsky K. Inducible gene targeting in mice. Science. 1995;269(5229):1427–9.CrossRefGoogle Scholar
  56. 56.
    Park D, Spencer JA, Koh BI, Kobayashi T, Fujisaki J, Clemens TL, et al. Endogenous bone marrow MSCs are dynamic, fate-restricted participants in bone maintenance and regeneration. Cell Stem Cell. 2012;10(3):259–72.CrossRefGoogle Scholar
  57. 57.
    Chee LC, Hendy J, Purton LE, McArthur GA. The granulocyte-colony stimulating factor receptor (G-CSFR) interacts with retinoic acid receptors (RARs) in the regulation of myeloid differentiation. J Leukoc Biol. 2013;93(2):235–43.CrossRefGoogle Scholar
  58. 58.
    Trumpp A, Depew MJ, Rubenstein JL, Bishop JM, Martin GR. Cre-mediated gene inactivation demonstrates that FGF8 is required for cell survival and patterning of the first branchial arch. Genes Dev. 1999;13(23):3136–48.CrossRefGoogle Scholar
  59. 59.
    Rodda SJ, McMahon AP. Distinct roles for hedgehog and canonical Wnt signaling in specification, differentiation and maintenance of osteoblast progenitors. Development. 2006;133(16):3231–44.CrossRefGoogle Scholar
  60. 60.
    Logan M, Martin JF, Nagy A, Lobe C, Olson EN, Tabin CJ. Expression of Cre recombinase in the developing mouse limb bud driven by a Prxl enhancer. Genesis. 2002;33(2):77–80.CrossRefGoogle Scholar
  61. 61.
    Muller SM, Stolt CC, Terszowski G, Blum C, Amagai T, Kessaris N, et al. Neural crest origin of perivascular mesenchyme in the adult thymus. J Immunol. 2008;180(8):5344–51.CrossRefGoogle Scholar
  62. 62.
    •• Green AC, Rudolph-Stringer V, Straszkowski L, Tjin G, Crimeen-Irwin B, Walia M, et al. Retinoic acid receptor γ activity in mesenchymal stem cells regulates endochondral bone, angiogenesis and B lymphopoiesis. J Bone Miner Res 2018;in press. Reveals that RARγ activity in limb bud mesenchymal stem cell-derived microenvironment cells alters the trabecular bone, chondrocytes, bone marrow sinusoids, and B lymphocytes in mice. Google Scholar
  63. 63.
    Dzhagalov I, Chambon P, He YW. Regulation of CD8+ T lymphocyte effector function and macrophage inflammatory cytokine production by retinoic acid receptor gamma. Journal of immunology. 2007;178(4):2113–21.CrossRefGoogle Scholar
  64. 64.
    Hall JA, Cannons JL, Grainger JR, Dos Santos LM, Hand TW, Naik S, et al. Essential role for retinoic acid in the promotion of CD4(+) T cell effector responses via retinoic acid receptor alpha. Immunity. 2011;34(3):435–47.CrossRefGoogle Scholar
  65. 65.
    Szilvassy SJ, Humphries RK, Lansdorp PM, Eaves AC, Eaves CJ. Quantitative assay for totipotent reconstituting hematopoietic stem cells by a competitive repopulation strategy. Proc Natl Acad Sci U S A. 1990;87(22):8736–40.CrossRefGoogle Scholar
  66. 66.
    Purton LE, Scadden DT. Limiting factors in murine hematopoietic stem cell assays. Cell Stem Cell. 2007;1(3):263–70.CrossRefGoogle Scholar
  67. 67.
    Moore KA, Ema H, Lemischka IR. In vitro maintenance of highly purified, transplantable hematopoietic stem cells. Blood. 1997;89(12):4337–47.PubMedGoogle Scholar
  68. 68.
    Nolta JA, Thiemann FT, Arakawa-Hoyt J, Dao MA, Barsky LW, Moore KA, et al. The AFT024 stromal cell line supports long-term ex vivo maintenance of engrafting multipotent human hematopoietic progenitors. Leukemia. 2002;16(3):352–61.CrossRefGoogle Scholar
  69. 69.
    Lewis ID, Almeida-Porada G, Du J, Lemischka IR, Moore KA, Zanjani ED, et al. Umbilical cord blood cells capable of engrafting in primary, secondary, and tertiary xenogeneic hosts are preserved after ex vivo culture in a noncontact system. Blood. 2001;97(11):3441–9.CrossRefGoogle Scholar
  70. 70.
    Chateauvieux S, Ichante JL, Delorme B, Frouin V, Pietu G, Langonne A, et al. Molecular profile of mouse stromal mesenchymal stem cells. Physiol Genomics. 2007;29(2):128–38.CrossRefGoogle Scholar
  71. 71.
    •• Cabezas-Wallscheid N, Buettner F, Sommerkamp P, Klimmeck D, Ladel L, Thalheimer FB, et al. Vitamin A-retinoic acid signaling regulates hematopoietic stem cell dormancy. Cell. 2017;169(5):807–23 e19. Shows that vitamin A regulates HSC dormancy. CrossRefGoogle Scholar
  72. 72.
    Leung AY, Verfaillie CM. All-trans retinoic acid (ATRA) enhances maintenance of primitive human hematopoietic progenitors and skews them towards myeloid differentiation in a stroma-noncontact culture system. Exp Hematol. 2005;33(4):422–7.CrossRefGoogle Scholar
  73. 73.
    Cheung AM, Tam CK, Chow HC, Verfaillie CM, Liang R, Leung AY. All-trans retinoic acid induces proliferation of an irradiated stem cell supporting stromal cell line AFT024. Exp Hematol. 2007;35(1):56–63.CrossRefGoogle Scholar
  74. 74.
    •• Ghiaur G, Yegnasubramanian S, Perkins B, Gucwa JL, Gerber JM, Jones RJ. Regulation of human hematopoietic stem cell self-renewal by the microenvironment’s control of retinoic acid signaling. Proc Natl Acad Sci U S A. 2013;110(40):16121–6. Reveals that microenvironment-produced CYP26 regulates human HSC maintenance. CrossRefGoogle Scholar
  75. 75.
    • Alonso S, Jones RJ, Ghiaur G. Retinoic acid, CYP26, and drug resistance in the stem cell niche. Exp Hematol. 2017;54:17–25. A review of the roles of CYP26 in the HSC niche. CrossRefGoogle Scholar
  76. 76.
    Yoshida H, Hayashi S, Kunisada T, Ogawa M, Nishikawa S, Okamura H, et al. The murine mutation osteopetrosis is in the coding region of the macrophage colony stimulating factor gene. Nature. 1990;345(6274):442–4.CrossRefGoogle Scholar
  77. 77.
    Nakano T, Kodama H, Honjo T. Generation of lymphohematopoietic cells from embryonic stem cells in culture. Science. 1994;265(5175):1098–101.CrossRefGoogle Scholar
  78. 78.
    Gao J, Yan XL, Li R, Liu Y, He W, Sun S, et al. Characterization of OP9 as authentic mesenchymal stem cell line. J Genet Genomics. 2010;37(7):475–82.CrossRefGoogle Scholar
  79. 79.
    Wolins NE, Quaynor BK, Skinner JR, Tzekov A, Park C, Choi K, et al. OP9 mouse stromal cells rapidly differentiate into adipocytes: characterization of a useful new model of adipogenesis. J Lipid Res. 2006;47(2):450–60.CrossRefGoogle Scholar
  80. 80.
    Sugiki T, Uyama T, Toyoda M, Morioka H, Kume S, Miyado K, et al. Hyaline cartilage formation and enchondral ossification modeled with KUM5 and OP9 chondroblasts. J Cell Biochem. 2007;100(5):1240–54.CrossRefGoogle Scholar

Copyright information

© Springer Nature Switzerland AG 2018

Authors and Affiliations

  • Chacko Joseph
    • 1
    • 2
    • 3
  • Alanna C. Green
    • 1
    • 2
    • 4
    • 5
  • Diannita Kwang
    • 1
    • 2
  • Louise E. Purton
    • 1
    • 2
    Email author
  1. 1.Stem Cell Regulation UnitSt. Vincent’s Institute of Medical ResearchFitzroyAustralia
  2. 2.Department of Medicine at St Vincent’s HospitalThe University of MelbourneFitzroyAustralia
  3. 3.Faculty of Medicine, Nursing and Health SciencesMonash UniversityClaytonAustralia
  4. 4.Sheffield Myeloma Research Team, Department of Oncology and MetabolismThe University of SheffieldSheffieldUK
  5. 5.The Mellanby Centre for Bone ResearchSheffieldUK

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