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

Abstract

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.

• Authors: Tara McCray, Julian V Pacheco, Candice C Loitz, Jason Garcia, Bethany Baumann, Michael J Schlicht, Klara Valyi-Nagy, Michael R Abern, Larisa Nonn
• Journal: iScience (iScience) Vol. 24 Issue 1 Pg. 101974 (Jan 22 2021) ISSN: 2589-0042 [Electronic] United States
• PMID: 33458620 (Publication Type: Journal Article)
• Copyright: © 2020 The Author(s).