Chemically induced skin tumors arise from long-lived stem cells of the upper hair follicle.
basic_science · Level V
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- Record sourced from PubMed, PMID 42275467.
- Also identified by DOI 10.1126/science.adv8291.
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Abstract
The identification of the cancer cell of origin is a fundamental question in cancer biology. We used fluorescent lineage tracing of independent mouse skin stem cell populations, single cell transcriptomics, and Duplex sequencing, to identify the origin of chemically induced skin tumors. Tumors arose predominantly from <i>Lgr6+</i> and / or <i>Lrig1+</i> stem cells of the upper hair follicle, but only very rarely from the <i>Lgr5</i>+ and <i>Krt19</i>+ hair follicle bulge. <i>Lgr6</i>+ stem cells initiated by dimethylbenzanthracene responded to tumor promoter treatment resulting in clonal expansion of initiated cells carrying the canonical <i>Hras</i> Q61L mutation. Spontaneous mutations in <i>Kras</i> also clonally expanded, but did not generate tumors unless the <i>Hras</i> gene was deleted, thus revealing a competitive interaction between <i>Hras</i> and <i>Kras</i> pathways that influences clonal selection.