Origins of gliogenic stem cell populations within adult skin and bone marrow.

The generation of Schwann cells from precursors within adult skin and bone marrow is of significant clinical interest because of the opportunities for disease modelling and strategies for remyelination. Recent evidence has suggested that glial cells can be generated from (i) mesenchymal stem cells (MSCs) within adult bone marrow and (ii) skin-derived precursor cells (SKPs) within adult skin. However, there is a need to clarify the developmental mechanism whereby such multipotent adult stem cell populations generate glia. We used Wnt1-Cre/Rosa26R(LacZ) and Wnt1-Cre/Rosa26R(YFP) neural crest reporter mice to test the hypothesis that (i) MSCs and (ii) SKPs represent adult gliogenic precursor cells of neural crest origin. We demonstrate that, although labeled cells can be identified within long bone preparation, such cells are rarely found in marrow plugs. Moreover, we did not find evidence of a neural crest origin of bone marrow-derived MSCs and were not able to provide a developmental rationale for the derivation of glial cells from MSCs using this approach. In contrast, we provide robust evidence for the neural crest origin of SKPs derived from adult skin. These precursor cells reliably generate cells with a Schwann cell phenotype, expressing appropriate transcription factors and Schwann cell markers. We demonstrate multiple anatomical origins of gliogenic SKPs within adult skin. We conclude that SKPs, rather than bone marrow-derived MSCs, represent a more defined and developmentally rational source for the study and generation of Schwann cells from readily accessible adult tissues.