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Vitamin D is a determinant of mouse intestinal Lgr5 stem cell functions.

Authors
  • Peregrina, Karina
  • Houston, Michele
  • Daroqui, Cecilia
  • Dhima, Elena
  • Sellers, Rani S
  • Augenlicht, Leonard H
Type
Published Article
Journal
Carcinogenesis
Publisher
Oxford University Press
Publication Date
Jan 01, 2015
Volume
36
Issue
1
Pages
25–31
Identifiers
DOI: 10.1093/carcin/bgu221
PMID: 25344836
Source
Medline
License
Unknown

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.

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