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

13 Citations (Scopus)

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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Vitamin D
Stem Cells
Calcitriol Receptors
Diet
Neoplasms
Helper-Inducer T-Lymphocytes
Population
Rodentia
Homeostasis
Calcium
Food

ASJC Scopus subject areas

  • Cancer Research

Cite this

Vitamin D is a determinant of mouse intestinal Lgr5 stem cell functions. / Peregrina, Karina; Houston, Michele; Daroqui, Cecilia; Dhima, Elena; Sellers, Rani S.; Augenlicht, Leonard H.

In: Carcinogenesis, Vol. 36, No. 1, 01.01.2015, p. 25-31.

Research output: Contribution to journalArticle

Peregrina, K, Houston, M, Daroqui, C, Dhima, E, Sellers, RS & Augenlicht, LH 2015, 'Vitamin D is a determinant of mouse intestinal Lgr5 stem cell functions', Carcinogenesis, vol. 36, no. 1, pp. 25-31. https://doi.org/10.1093/carcin/bgu221
Peregrina, Karina ; Houston, Michele ; Daroqui, Cecilia ; Dhima, Elena ; Sellers, Rani S. ; Augenlicht, Leonard H. / Vitamin D is a determinant of mouse intestinal Lgr5 stem cell functions. In: Carcinogenesis. 2015 ; Vol. 36, No. 1. pp. 25-31.
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