Epidermal Tissue Adapts to Restrain Progenitors Carrying Clonal p53 Mutations.
Cell Stem Cell
; 23(5): 687-699.e8, 2018 11 01.
Article
in En
| MEDLINE
| ID: mdl-30269904
ABSTRACT
Aging human tissues, such as sun-exposed epidermis, accumulate a high burden of progenitor cells that carry oncogenic mutations. However, most progenitors carrying such mutations colonize and persist in normal tissue without forming tumors. Here, we investigated tissue-level constraints on clonal progenitor behavior by inducing a single-allele p53 mutation (Trp53R245W; p53∗/wt), prevalent in normal human epidermis and squamous cell carcinoma, in transgenic mouse epidermis. p53∗/wt progenitors initially outcompeted wild-type cells due to enhanced proliferation, but subsequently reverted toward normal dynamics and homeostasis. Physiological doses of UV light accelerated short-term expansion of p53∗/wt clones, but their frequency decreased with protracted irradiation, possibly due to displacement by UV-induced mutant clones with higher competitive fitness. These results suggest multiple mechanisms restrain the proliferation of p53∗/wt progenitors, thereby maintaining epidermal integrity.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Stem Cells
/
Tumor Suppressor Protein p53
/
Clone Cells
/
Epidermis
/
Epidermal Cells
/
Mutation
Limits:
Animals
Language:
En
Journal:
Cell Stem Cell
Year:
2018
Document type:
Article
Affiliation country:
United kingdom