Direct Genesis of Functional Rodent and Human Schwann Cells from Skin Mesenchymal Precursors

•Rodent dermal mesenchymal precursors differentiate into functional Schwann cells•Mesenchymal Schwann cells are highly similar to neural crest Schwann cells•SKPs can be made from human neural crest and mesodermal dermis•Human mesodermal foreskin SKPs differentiate into functional Schwann cells

SummaryRecent reports of directed reprogramming have raised questions about the stability of cell lineages. Here, we have addressed this issue, focusing upon skin-derived precursors (SKPs), a dermally derived precursor cell. We show by lineage tracing that murine SKPs from dorsal skin originate from mesenchymal and not neural crest-derived cells. These mesenchymally derived SKPs can, without genetic manipulation, generate functional Schwann cells, a neural crest cell type, and are highly similar at the transcriptional level to Schwann cells isolated from the peripheral nerve. This is not a mouse-specific phenomenon, since human SKPs that are highly similar at the transcriptome level can be made from neural crest-derived facial and mesodermally derived foreskin dermis and the foreskin SKPs can make myelinating Schwann cells. Thus, nonneural crest-derived mesenchymal precursors can differentiate into bona fide peripheral glia in the absence of genetic manipulation, suggesting that developmentally defined lineage boundaries are more flexible than widely thought.