Survivin promotes stem cell competence for skin cancer initiation [scRNA-seq]

Stem cells (SCs) and not progenitors (Ps) act as cells of origin of Basal Cell Carcinoma (BCC). The mechanisms promoting BCC formation in SCs or restricting tumour development in Ps are currently unknown. In this study, we transcriptionally profiled SCs and Ps and found that Survivin, a pleiotropic factor that promotes cell division and inhibits apoptosis was preferentially expressed in SCs. Using genetic gain and loss of function mouse models, we showed that Survivin deletion in oncogene-expressing SCs prevents BCC formation. Survivin overexpression renders Ps competent to BCC formation by promoting cell survival and division while preventing apoptosis and differentiation. We identified SGK1, as a key downstream factor of Survivin, and its inhibition prevents BCC formation. This study uncovers the role and mechanisms by which Survivin regulates the competence of SCs to initiate BCC formation promoting the survival of oncogene-expressing SCs and self-renewing division while restricting differentiation and apoptosis. Overall design: To investigate the role of Survivin in Basal Cell Carcinoma formation we FACS-isolated a) SmoM2-YFP-expressin cells cells from the Involucrin-CREER/Rosa-SmoM2 mice and b) cells expressing SmoM2-YFP and Survivin-mCharry in cells from Involucrin-CREER/Rosa-SmoM2/Krt14rtTA/Survivin GOF mice. We performed single cell RNA seq in the FACS-isolated cells.