Single luminal epithelial progenitors can generate prostate organoids in culture

Chee Wai Chua, Maho Shibata, Ming Lei, Roxanne Toivanen, Lamont J. Barlow, Sarah K. Bergren, Ketan K. Badani, James M. McKiernan, Mitchell C. Benson, Hanina Hibshoosh, Michael M Shen

Research output: Contribution to journalArticleResearchpeer-review

Abstract

The intrinsic ability to exhibit self-organizing morphogenetic properties in ex vivo culture may represent a general property of tissue stem cells. Here we show that single luminal stem/progenitor cells can generate prostate organoids in a three-dimensional culture system in the absence of stroma. Organoids generated from CARNs (castration-resistant Nkx3.1-expressing cells) or normal prostate epithelia exhibit tissue architecture containing luminal and basal cells, undergo long-term expansion in culture and exhibit functional androgen receptor signalling. Lineage-tracing demonstrates that luminal cells are favoured for organoid formation and generate basal cells in culture. Furthermore, tumour organoids can initiate from CARNs after oncogenic transformation and from mouse models of prostate cancer, and can facilitate analyses of drug response. Finally, we provide evidence supporting the feasibility of organoid studies of human prostate tissue. Our studies underscore the progenitor properties of luminal cells, and identify in vitro approaches for studying prostate biology.

Original languageEnglish
Pages (from-to)951-961
Number of pages11
JournalNature Cell Biology
Volume16
Issue number10
DOIs
Publication statusPublished - 1 Jan 2014
Externally publishedYes

Cite this

Chua, C. W., Shibata, M., Lei, M., Toivanen, R., Barlow, L. J., Bergren, S. K., ... Shen, M. M. (2014). Single luminal epithelial progenitors can generate prostate organoids in culture. Nature Cell Biology, 16(10), 951-961. https://doi.org/10.1038/ncb3047
Chua, Chee Wai ; Shibata, Maho ; Lei, Ming ; Toivanen, Roxanne ; Barlow, Lamont J. ; Bergren, Sarah K. ; Badani, Ketan K. ; McKiernan, James M. ; Benson, Mitchell C. ; Hibshoosh, Hanina ; Shen, Michael M. / Single luminal epithelial progenitors can generate prostate organoids in culture. In: Nature Cell Biology. 2014 ; Vol. 16, No. 10. pp. 951-961.
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Chua, CW, Shibata, M, Lei, M, Toivanen, R, Barlow, LJ, Bergren, SK, Badani, KK, McKiernan, JM, Benson, MC, Hibshoosh, H & Shen, MM 2014, 'Single luminal epithelial progenitors can generate prostate organoids in culture' Nature Cell Biology, vol. 16, no. 10, pp. 951-961. https://doi.org/10.1038/ncb3047

Single luminal epithelial progenitors can generate prostate organoids in culture. / Chua, Chee Wai; Shibata, Maho; Lei, Ming; Toivanen, Roxanne; Barlow, Lamont J.; Bergren, Sarah K.; Badani, Ketan K.; McKiernan, James M.; Benson, Mitchell C.; Hibshoosh, Hanina; Shen, Michael M.

In: Nature Cell Biology, Vol. 16, No. 10, 01.01.2014, p. 951-961.

Research output: Contribution to journalArticleResearchpeer-review

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