Merkel Cell Polyomavirus T Antigen-Mediated Reprogramming in Adult Merkel Cell Progenitors

Whether Merkel cells regenerate in adult skin and from which progenitor cells they regenerate are a subject of debate. Understanding Merkel cell regeneration is of interest to the study of Merkel cell carcinoma, a rare neuroendocrine skin cancer hypothesized to originate in a Merkel cell progenitor transformed by Merkel cell polyomavirus small and large T antigens. We sought to understand what the adult Merkel cell progenitors are and whether they can give rise to Merkel cell carcinoma. We used lineage tracing to identify SOX9-expressing cells (SOX9+ cells) as Merkel cell progenitors in postnatal murine skin. Merkel cell regeneration from SOX9+ progenitors occurs rarely in mature skin unless in response to minor mechanical injury. Merkel cell polyomavirus small T antigen and functional imitation of large T antigen in SOX9+ cells enforced neuroendocrine and Merkel cell lineage reprogramming in a subset of cells. These results identify SOX9+ cells as postnatal Merkel cell progenitors that can be reprogrammed by Merkel cell polyomavirus T antigens to express neuroendocrine markers.

Automated summary

The regeneration of Merkel cells in adult skin and their origin from progenitor cells have been debated topics. Understanding Merkel cell regeneration is crucial for the study of Merkel cell carcinoma, a rare skin cancer, and its association with Merkel cell progenitors and polyomavirus. This study identified SOX9+ cells as postnatal Merkel cell progenitors and showed that they can be reprogrammed to express neuroendocrine markers by Merkel cell polyomavirus T antigens.