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

Karina Peregrina, Michele Houston, Cecilia Daroqui, Elena Dhima, Rani S. Sellers, Leonard H. Augenlicht

Research output: Contribution to journalArticle

14 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)25-31
Number of pages7
JournalCarcinogenesis
Volume36
Issue number1
DOIs
StatePublished - Jan 1 2015

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ASJC Scopus subject areas

  • Cancer Research

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