Vitamin D sufficiency enhances differentiation of patient-derived prostate epithelial organoids

• Published in: iScience 2021-01, Vol.24 (1), p.101974-101974, Article 101974
• Main Authors: McCray, Tara, Pacheco, Julian V., Loitz, Candice C., Garcia, Jason, Baumann, Bethany, Schlicht, Michael J., Valyi-Nagy, Klara, Abern, Michael R., Nonn, Larisa
• Format: Article
• Language: English
• Subjects: Cell Biology; Developmental Biology; Transcriptomics
• ISSN: 2589-0042; 2589-0042
• DOI: 10.1016/j.isci.2020.101974

Vitamin D is an essential steroid hormone that regulates systemic calcium homeostasis and cell fate decisions. The prostate gland is hormonally regulated, requiring steroids for proliferation and differentiation of secretory luminal cells. Vitamin D deficiency is associated with an increased risk of lethal prostate cancer, which exhibits a dedifferentiated pathology, linking vitamin D sufficiency to epithelial differentiation. To determine vitamin D regulation of prostatic epithelial differentiation, patient-derived benign prostate epithelial organoids were grown in vitamin D-deficient or -sufficient conditions. Organoids were assessed by phenotype and single-cell RNA sequencing. Mechanistic validation demonstrated that vitamin D sufficiency promoted organoid growth and accelerated differentiation by inhibiting canonical Wnt activity and suppressing Wnt family member DKK3. Wnt and DKK3 were also reduced by vitamin D in prostate tissue explants by spatial transcriptomics. Wnt dysregulation is a known contributor to aggressive prostate cancer, thus findings further link vitamin D deficiency to lethal disease. [Display omitted] •Vitamin D sufficiency accelerates differentiation of patient-derived prostate organoids•Single-cell RNAseq of organoids reveals differentiation trajectory over time•Vitamin D inhibits canonical Wnt activity in human prostate organoids and explants•Inhibition of DKK3 by vitamin D promotes organoid growth and proliferation Cell Biology; Developmental Biology; Transcriptomics