title: Single luminal epithelial progenitors can generate prostate organoids in culture.
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.
authors.affiliation: 1] Department of Medicine, Herbert Irving Comprehensive Cancer Center, Columbia University College of Physicians and Surgeons, New York, New York 10032, USA [2] Department of Genetics and Development, Herbert Irving Comprehensive Cancer Center, Columbia University College of Physicians and Surgeons, New York, New York 10032, USA [3] Department of Systems Biology, Herbert Irving Comprehensive Cancer Center, Columbia University College of Physicians and Surgeons, New York, New York 10032, USA [4] Department of Urology, Herbert Irving Comprehensive Cancer Center, Columbia University College of Physicians and Surgeons, New York, New York 10032, USA.
authors.forename: Chee Wai
authors.initials: CW
authors.lastname: Chua
authors.affiliation: 1] Department of Medicine, Herbert Irving Comprehensive Cancer Center, Columbia University College of Physicians and Surgeons, New York, New York 10032, USA [2] Department of Genetics and Development, Herbert Irving Comprehensive Cancer Center, Columbia University College of Physicians and Surgeons, New York, New York 10032, USA [3] Department of Systems Biology, Herbert Irving Comprehensive Cancer Center, Columbia University College of Physicians and Surgeons, New York, New York 10032, USA [4] Department of Urology, Herbert Irving Comprehensive Cancer Center, Columbia University College of Physicians and Surgeons, New York, New York 10032, USA.
authors.forename: Maho
authors.initials: M
authors.lastname: Shibata
authors.affiliation: 1] Department of Medicine, Herbert Irving Comprehensive Cancer Center, Columbia University College of Physicians and Surgeons, New York, New York 10032, USA [2] Department of Genetics and Development, Herbert Irving Comprehensive Cancer Center, Columbia University College of Physicians and Surgeons, New York, New York 10032, USA [3] Department of Systems Biology, Herbert Irving Comprehensive Cancer Center, Columbia University College of Physicians and Surgeons, New York, New York 10032, USA [4] Department of Urology, Herbert Irving Comprehensive Cancer Center, Columbia University College of Physicians and Surgeons, New York, New York 10032, USA.
authors.forename: Ming
authors.initials: M
authors.lastname: Lei
authors.affiliation: 1] Department of Medicine, Herbert Irving Comprehensive Cancer Center, Columbia University College of Physicians and Surgeons, New York, New York 10032, USA [2] Department of Genetics and Development, Herbert Irving Comprehensive Cancer Center, Columbia University College of Physicians and Surgeons, New York, New York 10032, USA [3] Department of Systems Biology, Herbert Irving Comprehensive Cancer Center, Columbia University College of Physicians and Surgeons, New York, New York 10032, USA [4] Department of Urology, Herbert Irving Comprehensive Cancer Center, Columbia University College of Physicians and Surgeons, New York, New York 10032, USA.
authors.forename: Roxanne
authors.initials: R
authors.lastname: Toivanen
authors.affiliation: Department of Urology, Herbert Irving Comprehensive Cancer Center, Columbia University College of Physicians and Surgeons, New York, New York 10032, USA.
authors.forename: LaMont J
authors.initials: LJ
authors.lastname: Barlow
authors.affiliation: 1] Department of Medicine, Herbert Irving Comprehensive Cancer Center, Columbia University College of Physicians and Surgeons, New York, New York 10032, USA [2] Department of Genetics and Development, Herbert Irving Comprehensive Cancer Center, Columbia University College of Physicians and Surgeons, New York, New York 10032, USA [3] Department of Systems Biology, Herbert Irving Comprehensive Cancer Center, Columbia University College of Physicians and Surgeons, New York, New York 10032, USA [4] Department of Urology, Herbert Irving Comprehensive Cancer Center, Columbia University College of Physicians and Surgeons, New York, New York 10032, USA.
authors.forename: Sarah K
authors.initials: SK
authors.lastname: Bergren
authors.affiliation: Department of Urology, Herbert Irving Comprehensive Cancer Center, Columbia University College of Physicians and Surgeons, New York, New York 10032, USA.
authors.forename: Ketan K
authors.initials: KK
authors.lastname: Badani
authors.affiliation: Department of Urology, Herbert Irving Comprehensive Cancer Center, Columbia University College of Physicians and Surgeons, New York, New York 10032, USA.
authors.forename: James M
authors.initials: JM
authors.lastname: McKiernan
authors.affiliation: Department of Urology, Herbert Irving Comprehensive Cancer Center, Columbia University College of Physicians and Surgeons, New York, New York 10032, USA.
authors.forename: Mitchell C
authors.initials: MC
authors.lastname: Benson
authors.affiliation: Department of Pathology and Cell Biology, Herbert Irving Comprehensive Cancer Center, Columbia University College of Physicians and Surgeons, New York, New York 10032, USA.
authors.forename: Hanina
authors.initials: H
authors.lastname: Hibshoosh
authors.affiliation: 1] Department of Medicine, Herbert Irving Comprehensive Cancer Center, Columbia University College of Physicians and Surgeons, New York, New York 10032, USA [2] Department of Genetics and Development, Herbert Irving Comprehensive Cancer Center, Columbia University College of Physicians and Surgeons, New York, New York 10032, USA [3] Department of Systems Biology, Herbert Irving Comprehensive Cancer Center, Columbia University College of Physicians and Surgeons, New York, New York 10032, USA [4] Department of Urology, Herbert Irving Comprehensive Cancer Center, Columbia University College of Physicians and Surgeons, New York, New York 10032, USA.
authors.forename: Michael M
authors.initials: MM
authors.lastname: Shen
mesh_terms: D000818:Animals; D018929:Cell Culture Techniques; D045744:Cell Line, Tumor; D019070:Cell Lineage; D002478:Cells, Cultured; D004847:Epithelial Cells / Q000166:cytology* / Q000378:metabolism; D005434:Flow Cytometry; D018398:Homeodomain Proteins / Q000378:metabolism; D006801:Humans; D008164:Luminescent Proteins / Q000235:genetics / Q000378:metabolism; D008297:Male; D057507:Mice, 129 Strain; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D008856:Microscopy, Fluorescence; D009940:Organoids / Q000166:cytology* / Q000378:metabolism; D010641:Phenotype; D011467:Prostate / Q000166:cytology* / Q000378:metabolism; D064129:Prostatic Neoplasms, Castration-Resistant / Q000378:metabolism / Q000473:pathology; D059010:Single-Cell Analysis / Q000379:methods; D013234:Stem Cells / Q000166:cytology* / Q000378:metabolism; D013997:Time Factors; D014157:Transcription Factors / Q000378:metabolism
chemical_list: D018398:Homeodomain Proteins; D008164:Luminescent Proteins; C491178:NKX3-1 protein, human; D014157:Transcription Factors