| First Author | Peregrina K | Year | 2015 |
| Journal | Carcinogenesis | Volume | 36 |
| Issue | 1 | Pages | 25-31 |
| PubMed ID | 25344836 | Mgi Jnum | J:218278 |
| Mgi Id | MGI:5617108 | Doi | 10.1093/carcin/bgu221 |
| Citation | Peregrina K, et al. (2015) Vitamin D is a determinant of mouse intestinal Lgr5 stem cell functions. Carcinogenesis 36(1):25-31 |
| abstractText | 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. |
