Skeletal muscle pericyte subtypes differ in their differentiation potential

Neural progenitor cells have been proposed as a therapy for central nervous system disorders, including neurodegenerative diseases and trauma injuries, however their accessibility is a major limitation. We recently isolated Tuj1+ cells from skeletal muscle culture of Nestin-GFP transgenic mice however whether they form functional neurons in the brain is not yet known. Additionally, their isolation from nontransgenic species and identification of their ancestors is unknown. This gap of knowledge precludes us from studying their role as a valuable alternative to neural progenitors. Here, we identified two pericyte subtypes, type-1 and type-2, using a double transgenic Nestin-GFP/NG2-DsRed mouse and demonstrated that Nestin-GFP+/Tuj1+ cells derive from type-2 Nestin-GFP+/NG2-DsRed+/CD146+ pericytes located in the skeletal muscle interstitium. These cells are bipotential as they generate either Tuj1+ cells when cultured with muscle cells or become "classical" α-SMA+pericytes when cultured alone. In contrast, type-1 Nestin-GFP-/NG2-DsRed+/CD146+ pericytes generate α-SMA+pericytes but not Tuj1+ cells. Interestingly, type-2 pericyte derived Tuj1+ cells retain some pericytic markers (CD146+/PDGFRβ+/NG2+). Given the potential application of Nestin-GFP+/NG2-DsRed+/Tuj1+ cells for cell therapy, we found a surface marker, the nerve growth factor receptor, which is expressed exclusively in these cells and can be used to identify and isolate them from mixed cell populations in nontransgenic species for clinical purposes.