Vitamin D differentially regulates colon stem cells in patient-derived normal and tumor organoids.

ABSTRACT: Intestine is a major target of vitamin D and several studies indicate an association between vitamin D deficiency and inflammatory bowel diseases (IBD), but also increased colorectal cancer (CRC) risk and mortality. However, the putative effects of 1α,25-dihydroxyvitamin D₃ (calcitriol), the active vitamin D metabolite, on human colonic stem cells are unknown. Here we show by immunohistochemistry and RNAscope in situ hybridization that vitamin D receptor (VDR) is unexpectedly expressed in LGR5⁺ colon stem cells in human tissue and in normal and tumor organoid cultures generated from patient biopsies. Interestingly, normal and tumor organoids respond differentially to calcitriol with profound and contrasting changes in their transcriptomic profiles. In normal organoids

SUBMITTER: Fernandez-Barral A 

PROVIDER: S-EPMC6972655 | biostudies-literature | 2020 Jan

REPOSITORIES: biostudies-literature