Direct Cellular Reprogramming Enables Development of Viral T Antigen-Driven Merkel Cell Carcinoma in Mice
February 2022
in “
The Journal of clinical investigation/The journal of clinical investigation
”
Merkel cell carcinoma MCC Merkel cell polyomavirus MCPyV viral transforming antigens TAgs ATOH1 p53 Trp53 gene hair follicles skin tumors tumorigenesis apoptosis transcriptome analysis Merkel cell cancer skin cancer polyomavirus tumor antigens transcription factor gene p53 hair roots tumor growth cell death gene expression analysis
TLDR Scientists made a mouse model of a serious skin cancer by changing skin cells with a virus and a specific gene, which is similar to the disease in humans.
The study demonstrates that direct cellular reprogramming using the transcription factor ATOH1 and Merkel cell polyomavirus (MCPyV) T antigens can induce the development of Merkel cell carcinoma (MCC) in mice. Researchers found that tumor initiation occurred near hair follicles, and progression to full-blown MCC required the deletion of the p53 gene. In SLAP mice, 8 out of 14 developed tumors resembling human MCCs within 11-22 weeks. These tumors exhibited similarities to human MCCs, including key markers and transcriptomic profiles. The findings highlight the role of MCPyV T antigens in MCC pathogenesis and suggest that complete loss of p53 is necessary for tumor expansion.
