title: Vitamin D is a determinant of mouse intestinal Lgr5 stem cell functions.
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.
authors.affiliation: Department of Medicine, Albert Einstein College of Medicine, Bronx, NY 10461, USA.
authors.forename: Karina
authors.initials: K
authors.lastname: Peregrina
authors.affiliation: Department of Medicine, Albert Einstein College of Medicine, Bronx, NY 10461, USA.
authors.forename: Michele
authors.initials: M
authors.lastname: Houston
authors.affiliation: Clinica Reina Fabiola, Oncativo 1248, Cordoba 5004, Argentina.
authors.forename: Cecilia
authors.initials: C
authors.lastname: Daroqui
authors.affiliation: Department of Medicine, Albert Einstein College of Medicine, Bronx, NY 10461, USA.
authors.forename: Elena
authors.initials: E
authors.lastname: Dhima
authors.affiliation: Department of Pathology and.
authors.forename: Rani S
authors.initials: RS
authors.lastname: Sellers
authors.affiliation: Department of Medicine, Albert Einstein College of Medicine, Bronx, NY 10461, USA, Department of Cell Biology, Albert Einstein College of Medicine, Bronx, NY 10461, USA leonard.augenlicht@einstein.yu.edu.
authors.forename: Leonard H
authors.initials: LH
authors.lastname: Augenlicht
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects*; D049109:Cell Proliferation; D002478:Cells, Cultured; D019587:Dietary Supplements; D006801:Humans; D007124:Immunoenzyme Techniques; D007413:Intestinal Mucosa / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D043562:Receptors, G-Protein-Coupled / Q000502:physiology*; D013234:Stem Cells / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D014807:Vitamin D / Q000008:administration & dosage*; D014815:Vitamins / Q000008:administration & dosage
chemical_list: C493597:Lgr5 protein, mouse; D043562:Receptors, G-Protein-Coupled; D014815:Vitamins; D014807:Vitamin D