Chemically induced skin tumors arise from long-lived stem cells of the upper hair follicle
- Eve Kandyba
- Arnaud Jabouille
- Ferriol Calvet
- Yun Rose Li
- Andrea Curtabbi
- Diana Cristea
- Joyce Shin
- Reyno Delrosario
- Jonathan Anzules
- Di Wu
- David Quigley
- Mark Taylor
- Camila Zanette
- Fang Yin Lo
- Jacob Higgins
- Jesse Salk
- Nuria Lopez-Bigas
- Allan Balmain
2026-06-11
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 Lgr6+ and / or Lrig1+ stem cells of the upper hair follicle, but only very rarely from the Lgr5 + and Krt19 + hair follicle bulge. Lgr6 + stem cells initiated by dimethylbenzanthracene responded to tumor promoter treatment resulting in clonal expansion of initiated cells carrying the canonical Hras Q61L mutation. Spontaneous mutations in Kras also clonally expanded, but did not generate tumors unless the Hras gene was deleted, thus revealing a competitive interaction between Hras and Kras pathways that influences clonal selection.