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

• DOI: 10.1111/febs.14998
• Publication Date: 2019-07-15T20:15:01Z
• Authors: Asunción Fernánde...; Alba Costales‐Car...; Sandra P. Buira; Peter Jung; Gemma Ferrer‐Mayorga; María Jesús Larriba; Pilar Bustamante‐...; Orlando Domínguez; Francisco X. Real; Laura Guerra‐Past...; Miguel Lafarga; Damián García‐Olmo; Ramón Cantero; Luis Del Peso; Eduard Batlle; Federico Rojo; Alberto Muñoz; Antonio Barbáchano
• Keywords: Organoid

Intestine is a major target of vitamin D and several studies indicate an association between deficiency inflammatory bowel diseases (IBD), but also increased colorectal cancer (CRC) risk mortality. However, the putative effects 1α,25-dihydroxyvitamin D3 (calcitriol), active metabolite, on human colonic stem cells are unknown. Here we show by immunohistochemistry RNAscope in situ hybridization that receptor (VDR) unexpectedly expressed LGR5+ colon tissue normal tumor organoid cultures generated from patient biopsies. Interestingly, organoids respond differentially to calcitriol with profound contrasting changes their transcriptomic profiles. In organoids, upregulates stemness-related genes, such as LGR5, SMOC2, LRIG1, MSI1, PTK7, MEX3A, inhibits cell proliferation. contrast, has little effect genes while it induces differentiated phenotype, variably reduces Concordantly, electron microscopy showed does not affect blastic undifferentiated phenotype series features organoids. Our results constitute first demonstration regulatory role cells, indicating homeostatic epithelium relevant implications IBD CRC.