Chemically induced skin tumors arise from long-lived stem cells of the upper hair follicle.
Not reported in abstract.
Where it sits
this study against the rest of the p21 (p021) corpusSummary and findings
Not reported in abstract.
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.
Background
Not reported in abstract.
Methods
Not reported in abstract.
Results
Not reported in abstract.
Interpretation
Not reported in abstract.
Limitations
Not reported in abstract.