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

Tara McCray; Julian V Pacheco; Candice C Loitz; Jason Garcia; Bethany Baumann; Michael J Schlicht; Klara Valyi-Nagy; Michael R Abern; Larisa Nonn

doi:10.1016/j.isci.2020.101974

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

iScience. 2021 Jan 5;24(1):101974. doi: 10.1016/j.isci.2020.101974. eCollection 2021 Jan 22.

Authors

Tara McCray¹, Julian V Pacheco¹, Candice C Loitz¹, Jason Garcia¹, Bethany Baumann¹, Michael J Schlicht^{1

2}, Klara Valyi-Nagy^{1

2}, Michael R Abern^{2

3}, Larisa Nonn^{1

2}

Affiliations

¹ Department of Pathology, University of Illinois at Chicago, 840 S Wood Street, Chicago, IL 60612, USA.
² University of Illinois Cancer Center, Chicago, IL 60612, USA.
³ Department of Urology, University of Illinois at Chicago, Chicago, IL 60612, USA.

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.

Keywords: Cell Biology; Developmental Biology; Transcriptomics.