A new twist on skin innervation: the role of peripheral glia in wound healing and tumor formation

Speaker: Lukas Sommer, University of Zurich, Switzerland

A major research focus of our laboratory is the b iology of the neural crest, a transient embryonic stem cell population endowed with one of the b roadest developmental potentials in vivo. Using mouse models in conjunction with functional ana lyses in stem cell cultures, we identified molecular mechanisms regulating self-renewal and fate dec isions of NCSCs during embryonic development. Intriguingly, we were able to isolate cells very si milar to NCSCs from adult murine and human skin. Genetic lineage tracing and gene depletion technologies revealed that such NCSC-like cells emerge by injury-induced dedifferentiation of peripheral g  lial cells in vivo and support skin wound healing by secretion of a plethora of tissue repair factors associated with inflammation, angiogenesis, ECM remodeling, and other processes previously implicated in wound healing. Strikingly, similar dedifferentiated glia are also found in premalignant lesions and the stroma of established human and murine cutaneous squamous cell carcinoma (cSCC). We demonstrate that these tumor-associated glial cells (TAGs) are crucial for cSCC formation by regulating the cellular crosstalk in the tumor microenvironment. As almost all tumors are innervated and, hence, harbor peripheral glia, it is conceivable that our findings are also relevant for cancers of tissues other than the skin.