The significance and application of vascular niche in the development and maintenance of hematopoietic stem cells

Progress in Hematology The regulatory signal for normal and abnormal hematopoiesis


Deriving hematopoietic stem cells (HSCs) from human pluripotent stem cells is one of major goals in stem cell and hematological research. To induce HSCs from human pluripotent stem cells, many attempts to mimic embryonic development through stepwise exposure to morphogens. HSCs arise from dorsal aorta of embryos then migrate and settle in the bone marrow. Development and maintenance of HSCs are controlled by the microenvironmental cues around the blood vessels (called vascular niche) through morphogens and cytokines. Vascular niche serves as a common mechanism from embryo development to life-long maintenance of HSCs. In this chapter, I discuss that how vascular niche regulates development and maintenance of HSCs and exemplify the role of vascular niche to exquisitely induce HSCs from human pluripotent stem cells.


Hematopoietic stem cell Pluripotent stem cell Niche Transcriptional regulation Signaling 


  1. 1.
    Morrison SJ, Scadden DT. The bone marrow niche for haematopoietic stem cells. Nature. 2014;505:327–34. Scholar
  2. 2.
    Kiel MJ, et al. SLAM family receptors distinguish hematopoietic stem and progenitor cells and reveal endothelial niches for stem cells. Cell. 2005;121:1109–21. Scholar
  3. 3.
    Kunisaki Y, et al. Arteriolar niches maintain haematopoietic stem cell quiescence. Nature. 2013;502:637–43. Scholar
  4. 4.
    Omatsu Y, Seike M, Sugiyama T, Kume T, Nagasawa T. Foxc1 is a critical regulator of haematopoietic stem/progenitor cell niche formation. Nature. 2014;508:536–40. Scholar
  5. 5.
    Sugimura R. Bioengineering hematopoietic stem cell niche toward regenerative medicine. Adv Drug Deliv Rev. 2016;99:212–20. Scholar
  6. 6.
    Medvinsky A, Dzierzak E. Definitive hematopoiesis is autonomously initiated by the AGM region. Cell. 1996;86:897–906.CrossRefPubMedGoogle Scholar
  7. 7.
    Ivanovs A, et al. Highly potent human hematopoietic stem cells first emerge in the intraembryonic aorta-gonad-mesonephros region. J Exp Med. 2011;208:2417–27. Scholar
  8. 8.
    Ng ES, et al. Differentiation of human embryonic stem cells to HOXA + hemogenic vasculature that resembles the aorta-gonad-mesonephros. Nat Biotechnol. 2016;34:1168–79. Scholar
  9. 9.
    Gomes AC, et al. Hematopoietic stem cell niches produce lineage-instructive signals to control multipotent progenitor differentiation. Immunity. 2016;45:1219–31. Scholar
  10. 10.
    Fares I, et al. Cord blood expansion. Pyrimidoindole derivatives are agonists of human hematopoietic stem cell self-renewal. Science. 2014;345:1509–12. Scholar
  11. 11.
    Reinisch A, et al. A humanized bone marrow ossicle xenotransplantation model enables improved engraftment of healthy and leukemic human hematopoietic cells. Nat Med. 2016;22:812–21. Scholar
  12. 12.
    Sugimura R, et al. Haematopoietic stem and progenitor cells from human pluripotent stem cells. Nature. 2017. Scholar
  13. 13.
    Lis R, et al. Conversion of adult endothelium to immunocompetent haematopoietic stem cells. Nature. 2017. Scholar

Copyright information

© The Japanese Society of Hematology 2018

Authors and Affiliations

  1. 1.Stem Cell Transplantation Program, Division of Pediatric Hematology and OncologyDana-Farber Cancer Institute, Boston Children’s HospitalBostonUSA

Personalised recommendations