Pleiotrophin Regulates the Retention and Self-Renewal of Hematopoietic Stem Cells in the Bone Marrow Vascular Niche

Division of Cellular Therapy, Department of Medicine, Duke University Medical Center, Duke University, Durham, NC 27710, USA.
Cell Reports (Impact Factor: 8.36). 10/2012; 2(4). DOI: 10.1016/j.celrep.2012.09.002
Source: PubMed


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.

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    • "Knockout of these proteins augments HSC function. However, their effects are non-autonomous and are rather due to their interaction with the bone marrow microenvironment (Himburg et al., 2012; Quarmyne et al., 2015). SHP2 and PRL2 are both intra-cytoplasmic phosphatases and have been shown to increase HSC self-renewal as opposed to STS1/STS2 (Chan et al., 2011; Kobayashi et al., 2014; Zhu et al., 2011). "
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