Interplay of opposing fate choices stalls oncogenic growth in murine skin epithelium.

ABSTRACT: Skin epithelium can accumulate a high burden of oncogenic mutations without morphological or functional consequences. To investigate the mechanism of oncogenic tolerance, we induced Hras^G12V in single murine epidermal cells and followed them long term. We observed that Hras^G12V promotes an early and transient clonal expansion driven by increased progenitor renewal that is replaced with an increase in progenitor differentiation leading to reduced growth. We attribute this dynamic effect to emergence of two populations within oncogenic clones: renewing progenitors along the edge and differentiating ones within the central core. As clone expansion is accompanied by progressive enlargement of the core and diminishment of the edge compartment, the intraclonal competition b

SUBMITTER: Sandoval M 

PROVIDER: S-EPMC7817173 | biostudies-literature | 2021 Jan

REPOSITORIES: biostudies-literature