2026-04-29T23:03:52Zhttps://repisalud.isciii.es/rest/oai/request

oai:repisalud.isciii.es:20.500.12105/181972024-11-29T15:02:50Zcom_20.500.12105_2173com_20.500.12105_2051col_20.500.12105_19597

00925njm 22002777a 4500 dc Fernández-Barral, Asunción author Costales-Carrera, Alba author Buira, Sandra P author Jung, Peter author Ferrer-Mayorga, Gemma author Larriba, María Jesús author Bustamante-Madrid, Pilar author Domínguez, Orlando author Real Arribas, Francisco author Guerra-Pastrián, Laura author Lafarga, Miguel author García-Olmo, Damián author Cantero, Ramón author Del Peso, Luis author Batlle, Eduard author Rojo, Federico author Muñoz, Alberto author Barbáchano, Antonio author 2020-01 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, calcitriol upregulates stemness-related genes, such as LGR5, SMOC2, LRIG1, MSI1, PTK7, and MEX3A, and inhibits cell proliferation. In contrast, in tumor organoids calcitriol has little effect on stemness-related genes while it induces a differentiated phenotype, and variably reduces cell proliferation. Concordantly, electron microscopy showed that calcitriol does not affect the blastic undifferentiated cell phenotype in normal organoids but it induces a series of differentiated features in tumor organoids. Our results constitute the first demonstration of a regulatory role of vitamin D on human colon stem cells, indicating a homeostatic effect on colon epithelium with relevant implications in IBD and CRC. FEBS J . 2020;287(1):53-72. 10.1111/febs.14998 1742-4658 The FEBS journal 31306552 http://hdl.handle.net/20.500.12105/18197 Vitamin D differentially regulates colon stem cells in patient-derived normal and tumor organoids.