Pleiotrophin regulates the retention and self-renewal of hematopoietic stem cells in the bone marrow vascular niche

Cell Rep. 2012 Oct 25;2(4):964-75. doi: 10.1016/j.celrep.2012.09.002. Epub 2012 Oct 19.

Abstract

The mechanisms through which the bone marrow (BM) microenvironment regulates hematopoietic stem cell (HSC) fate remain incompletely understood. We examined the role of the heparin-binding growth factor pleiotrophin (PTN) in regulating HSC function in the niche. PTN(-/-) mice displayed significantly decreased BM HSC content and impaired hematopoietic regeneration following myelosuppression. Conversely, mice lacking protein tyrosine phosphatase receptor zeta, which is inactivated by PTN, displayed significantly increased BM HSC content. Transplant studies revealed that PTN action was not HSC autonomous, but rather was mediated by the BM microenvironment. Interestingly, PTN was differentially expressed and secreted by BM sinusoidal endothelial cells within the vascular niche. Furthermore, systemic administration of anti-PTN antibody in mice substantially impaired both the homing of hematopoietic progenitor cells to the niche and the retention of BM HSCs in the niche. PTN is a secreted component of the BM vascular niche that regulates HSC self-renewal and retention in vivo.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Antibodies / immunology
  • Bone Marrow Cells / cytology*
  • Carrier Proteins / genetics
  • Carrier Proteins / metabolism*
  • Cells, Cultured
  • Chemokine CXCL12 / metabolism
  • Cytokines / deficiency
  • Cytokines / genetics
  • Cytokines / metabolism*
  • Hematopoietic Stem Cell Transplantation
  • Hematopoietic Stem Cells / cytology*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Receptor-Like Protein Tyrosine Phosphatases, Class 5 / metabolism
  • Stem Cell Niche

Substances

  • Antibodies
  • Carrier Proteins
  • Chemokine CXCL12
  • Cytokines
  • pleiotrophin
  • Ptprz1 protein, mouse
  • Receptor-Like Protein Tyrosine Phosphatases, Class 5