The stem cell regulator PEDF is dispensable for maintenance and function of hematopoietic stem cells

Pigment epithelium derived factor (PEDF), a ubiquitously expressed 50 kDa secreted glycoprotein, was recently discovered to regulate self-renewal of neural stem cells and have a supportive effect on human embryonic stem cell growth. Here, we analyzed expression of PEDF in the murine hematopoietic stem cell (HSC) compartments and found that PEDF is highly expressed in primary long-term HSCs. Therefore, we characterized the hematopoietic system in a knockout mouse model for PEDF and using this model we surprisingly found that PEDF is dispensable for HSC regulation. PEDF knockout mice exhibit normal hematopoiesis in steady state conditions and the absence of PEDF lead to normal regeneration capacity in a serial competitive transplantation setting. Additionally, PEDF-deficient cells exhibit unaltered lineage distribution upon serial transplantations. When human cord blood stem and progenitor cells were cultured in media supplemented with recombinant PEDF they did not show changes in growth potential. Taken together, we report that PEDF is not a critical regulatory factor for HSC function during regeneration in vivo or growth of human stem/progenitor cells in vitro.Funding Agencies|Hemato-Linne grant (Swedish Research Council Linnaeus); STEMTHERAPY (Swedish Research Council); Swedish Cancer Society (Cancerfonden); Swedish Childhood Cancer Foundation; Swedish Research Council; Royal Swedish Academy of Sciences - Tobias Foundation; Lund University Hospital (ALF grant); Royal Physiographic Society in Lund (Kungliga Fysiograftska sallskapet); center of excellence grant in Life Sciences from the Swedish Foundation for Strategic Research