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

Madison Weber, Minh Binh Nguyen, Meng Yen Li, Pooja Flora, Masahiro Shuda, Elena Ezhkova

Research output: Contribution to journalArticlepeer-review

2 Scopus citations

Abstract

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.

Original languageEnglish
Pages (from-to)2163-2176.e6
JournalJournal of Investigative Dermatology
Volume143
Issue number11
DOIs
StatePublished - Nov 2023

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