GPI-80 defines self-renewal ability in hematopoietic stem cells during human development

Cell Stem Cell. 2015 Jan 8;16(1):80-7. doi: 10.1016/j.stem.2014.10.020. Epub 2014 Nov 13.


Advances in pluripotent stem cell and reprogramming technologies have given us the hope of generating hematopoietic stem cells (HSCs) in culture. To succeed, greater understanding of the self-renewing HSC during human development is required. We discovered that the glycophosphatidylinositol-anchored surface protein GPI-80 defines a subpopulation of human fetal liver hematopoietic stem/progenitor cells (HSPCs) with self-renewal ability. CD34(+)CD38(lo/-)CD90(+)GPI-80(+) HSPCs were the sole population that maintained proliferative potential and an undifferentiated state in stroma coculture and engrafted in immunodeficient mice. GPI-80 expression also enabled tracking of HSPCs once they emerged from endothelium and migrated between human fetal hematopoietic niches. GPI-80 colocalized on the surface of HSPCs with Integrin alpha-M (ITGAM), which in leukocytes cooperates with GPI-80 to support migration. Knockdown of GPI-80 or ITGAM was sufficient to compromise HSPC expansion in culture and engraftment in vivo. These findings indicate that human fetal HSCs employ mechanisms used in leukocyte adhesion and migration to mediate HSC self-renewal.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Amidohydrolases / metabolism*
  • CD11b Antigen / metabolism
  • Cell Adhesion Molecules / metabolism*
  • Cell Differentiation
  • Cell Lineage
  • Cell Proliferation
  • Embryonic Development*
  • Fetus / cytology
  • Flow Cytometry
  • GPI-Linked Proteins / metabolism
  • Hematopoietic Stem Cell Transplantation
  • Hematopoietic Stem Cells / cytology*
  • Hematopoietic Stem Cells / metabolism*
  • Humans
  • Immunophenotyping
  • Liver / cytology
  • Liver / embryology


  • CD11b Antigen
  • Cell Adhesion Molecules
  • GPI-Linked Proteins
  • ITGAM protein, human
  • Amidohydrolases
  • VNN2 protein, human