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

Publication ,  Journal Article
McCray, T; Pacheco, JV; Loitz, CC; Garcia, J; Baumann, B; Schlicht, MJ; Valyi-Nagy, K; Abern, MR; Nonn, L
Published in: iScience
January 22, 2021

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.

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Published In

iScience

DOI

EISSN

2589-0042

Publication Date

January 22, 2021

Volume

24

Issue

1

Start / End Page

101974

Location

United States
 

Citation

APA
Chicago
ICMJE
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NLM
McCray, T., Pacheco, J. V., Loitz, C. C., Garcia, J., Baumann, B., Schlicht, M. J., … Nonn, L. (2021). Vitamin D sufficiency enhances differentiation of patient-derived prostate epithelial organoids. IScience, 24(1), 101974. https://doi.org/10.1016/j.isci.2020.101974
McCray, Tara, Julian V. Pacheco, Candice C. Loitz, Jason Garcia, Bethany Baumann, Michael J. Schlicht, Klara Valyi-Nagy, Michael R. Abern, and Larisa Nonn. “Vitamin D sufficiency enhances differentiation of patient-derived prostate epithelial organoids.IScience 24, no. 1 (January 22, 2021): 101974. https://doi.org/10.1016/j.isci.2020.101974.
McCray T, Pacheco JV, Loitz CC, Garcia J, Baumann B, Schlicht MJ, et al. Vitamin D sufficiency enhances differentiation of patient-derived prostate epithelial organoids. iScience. 2021 Jan 22;24(1):101974.
McCray, Tara, et al. “Vitamin D sufficiency enhances differentiation of patient-derived prostate epithelial organoids.IScience, vol. 24, no. 1, Jan. 2021, p. 101974. Pubmed, doi:10.1016/j.isci.2020.101974.
McCray T, Pacheco JV, Loitz CC, Garcia J, Baumann B, Schlicht MJ, Valyi-Nagy K, Abern MR, Nonn L. Vitamin D sufficiency enhances differentiation of patient-derived prostate epithelial organoids. iScience. 2021 Jan 22;24(1):101974.
Journal cover image

Published In

iScience

DOI

EISSN

2589-0042

Publication Date

January 22, 2021

Volume

24

Issue

1

Start / End Page

101974

Location

United States