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

Published

Journal Article

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.

Full Text

Duke Authors

Cited Authors

  • Himburg, HA; Harris, JR; Ito, T; Daher, P; Russell, JL; Quarmyne, M; Doan, PL; Helms, K; Nakamura, M; Fixsen, E; Herradon, G; Reya, T; Chao, NJ; Harroch, S; Chute, JP

Published Date

  • October 25, 2012

Published In

Volume / Issue

  • 2 / 4

Start / End Page

  • 964 - 975

PubMed ID

  • 23084748

Pubmed Central ID

  • 23084748

Electronic International Standard Serial Number (EISSN)

  • 2211-1247

Digital Object Identifier (DOI)

  • 10.1016/j.celrep.2012.09.002

Language

  • eng

Conference Location

  • United States