title: Identification of multipotent luminal progenitor cells in human prostate organoid cultures.
abstract: The prostate gland consists of basal and luminal cells arranged as pseudostratified epithelium. In tissue recombination models, only basal cells reconstitute a complete prostate gland, yet murine lineage-tracing experiments show that luminal cells generate basal cells. It has remained challenging to address the molecular details of these transitions and whether they apply to humans, due to the lack of culture conditions that recapitulate prostate gland architecture. Here, we describe a 3D culture system that supports long-term expansion of primary mouse and human prostate organoids, composed of fully differentiated CK5+ basal and CK8+ luminal cells. Organoids are genetically stable, reconstitute prostate glands in recombination assays, and can be experimentally manipulated. Single human luminal and basal cells give rise to organoids, yet luminal-cell-derived organoids more closely resemble prostate glands. These data support a luminal multilineage progenitor cell model for prostate tissue and establish a robust, scalable system for mechanistic studies.
authors.affiliation: Hubrecht Institute, Royal Netherlands Academy of Arts and Sciences and University Medical Center Utrecht, 3584 CT, Utrecht, Netherlands.
authors.forename: Wouter R
authors.initials: WR
authors.lastname: Karthaus
authors.affiliation: Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
authors.forename: Phillip J
authors.initials: PJ
authors.lastname: Iaquinta
authors.affiliation: Hubrecht Institute, Royal Netherlands Academy of Arts and Sciences and University Medical Center Utrecht, 3584 CT, Utrecht, Netherlands.
authors.forename: Jarno
authors.initials: J
authors.lastname: Drost
authors.affiliation: Hubrecht Institute, Royal Netherlands Academy of Arts and Sciences and University Medical Center Utrecht, 3584 CT, Utrecht, Netherlands.
authors.forename: Ana
authors.initials: A
authors.lastname: Gracanin
authors.affiliation: Hubrecht Institute, Royal Netherlands Academy of Arts and Sciences and University Medical Center Utrecht, 3584 CT, Utrecht, Netherlands.
authors.forename: Ruben
authors.initials: R
authors.lastname: van Boxtel
authors.affiliation: Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
authors.forename: John
authors.initials: J
authors.lastname: Wongvipat
authors.affiliation: Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
authors.forename: Catherine M
authors.initials: CM
authors.lastname: Dowling
authors.affiliation: Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
authors.forename: Dong
authors.initials: D
authors.lastname: Gao
authors.affiliation: Hubrecht Institute, Royal Netherlands Academy of Arts and Sciences and University Medical Center Utrecht, 3584 CT, Utrecht, Netherlands.
authors.forename: Harry
authors.initials: H
authors.lastname: Begthel
authors.affiliation: Hubrecht Institute, Royal Netherlands Academy of Arts and Sciences and University Medical Center Utrecht, 3584 CT, Utrecht, Netherlands.
authors.forename: Norman
authors.initials: N
authors.lastname: Sachs
authors.affiliation: Hubrecht Institute, Royal Netherlands Academy of Arts and Sciences and University Medical Center Utrecht, 3584 CT, Utrecht, Netherlands.
authors.forename: Robert G J
authors.initials: RGJ
authors.lastname: Vries
authors.affiliation: Hubrecht Institute, Royal Netherlands Academy of Arts and Sciences and University Medical Center Utrecht, 3584 CT, Utrecht, Netherlands.
authors.forename: Edwin
authors.initials: E
authors.lastname: Cuppen
authors.affiliation: Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
authors.forename: Yu
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA; Howard Hughes Medical Institute.
authors.forename: Charles L
authors.initials: CL
authors.lastname: Sawyers
authors.affiliation: Hubrecht Institute, Royal Netherlands Academy of Arts and Sciences and University Medical Center Utrecht, 3584 CT, Utrecht, Netherlands. Electronic address: h.clevers@hubrecht.eu.
authors.forename: Hans C
authors.initials: HC
authors.lastname: Clevers
mesh_terms: D000728:Androgens / Q000378:metabolism; D006801:Humans; D008297:Male; D009924:Organ Culture Techniques; D009940:Organoids; D011467:Prostate / Q000166:cytology*; D013234:Stem Cells / Q000166:cytology / Q000378:metabolism
chemical_list: D000728:Androgens