Vitamin D is a determinant of mouse intestinal Lgr5 stem cell functions.
Carcinogenesis
; 36(1): 25-31, 2015 Jan.
Article
en En
| MEDLINE
| ID: mdl-25344836
ABSTRACT
Lgr5+ intestinal crypt base columnar cells function as stem cells whose progeny populate the villi, and Lgr5+ cells in which Apc is inactivated can give rise to tumors. Surprisingly, these Lgr5+ stem cell properties were abrogated by the lower dietary vitamin D and calcium in a semi-purified diet that promotes both genetically initiated and sporadic intestinal tumors. Inactivation of the vitamin D receptor in Lgr5+ cells established that compromise of Lgr5 stem cell function was a rapid, cell autonomous effect of signaling through the vitamin D receptor. The loss of Lgr5 stem cell function was associated with presence of Ki67 negative Lgr5+ cells at the crypt base. Therefore, vitamin D, a common nutrient and inducer of intestinal cell maturation, is an environmental factor that is a determinant of Lgr5+ stem cell functions in vivo. Since diets used in reports that establish and dissect mouse Lgr5+ stem cell activity likely provided vitamin D levels well above the range documented for human populations, the contribution of Lgr5+ cells to intestinal homeostasis and tumor formation in humans may be significantly more limited, and variable in the population, then suggested by published rodent studies.
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Células Madre
/
Vitamina D
/
Diferenciación Celular
/
Receptores Acoplados a Proteínas G
/
Mucosa Intestinal
Límite:
Animals
/
Humans
Idioma:
En
Revista:
Carcinogenesis
Año:
2015
Tipo del documento:
Article
País de afiliación:
Estados Unidos