Identification of multipotent luminal progenitor cells in human prostate organoid cultures

Wouter R Karthaus; Phillip J Iaquinta; Jarno Drost; Ana Gracanin; Ruben van Boxtel; John Wongvipat; Catherine M Dowling; Dong Gao; Harry Begthel; Norman Sachs; Robert G J Vries; Edwin Cuppen; Yu Chen; Charles L Sawyers; Hans C Clevers

doi:10.1016/j.cell.2014.08.017

Identification of multipotent luminal progenitor cells in human prostate organoid cultures

Wouter R Karthaus, Phillip J Iaquinta, Jarno Drost, Ana Gracanin, Ruben van Boxtel, John Wongvipat, Catherine M Dowling, Dong Gao, Harry Begthel, Norman Sachs, Robert G J Vries, Edwin Cuppen, Yu Chen, Charles L Sawyers, Hans C Clevers

Hubrecht Institute

Research output: Contribution to journal/periodical › Article › Scientific › peer-review

563 Citations (Scopus)

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.

Original language	English
Pages (from-to)	163-75
Number of pages	13
Journal	Cell
Volume	159
Issue number	1
DOIs	https://doi.org/10.1016/j.cell.2014.08.017
Publication status	Published - 25 Sept 2014

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Karthaus, W. R., Iaquinta, P. J., Drost, J., Gracanin, A., van Boxtel, R., Wongvipat, J., Dowling, C. M., Gao, D., Begthel, H., Sachs, N., Vries, R. G. J., Cuppen, E., Chen, Y., Sawyers, C. L., & Clevers, H. C. (2014). Identification of multipotent luminal progenitor cells in human prostate organoid cultures. Cell, 159(1), 163-75. https://doi.org/10.1016/j.cell.2014.08.017

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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.",

author = "Karthaus, {Wouter R} and Iaquinta, {Phillip J} and Jarno Drost and Ana Gracanin and {van Boxtel}, Ruben and John Wongvipat and Dowling, {Catherine M} and Dong Gao and Harry Begthel and Norman Sachs and Vries, {Robert G J} and Edwin Cuppen and Yu Chen and Sawyers, {Charles L} and Clevers, {Hans C}",

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AU - Karthaus, Wouter R

AU - Iaquinta, Phillip J

AU - Drost, Jarno

AU - Gracanin, Ana

AU - van Boxtel, Ruben

AU - Wongvipat, John

AU - Dowling, Catherine M

AU - Gao, Dong

AU - Begthel, Harry

AU - Sachs, Norman

AU - Vries, Robert G J

AU - Cuppen, Edwin

AU - Chen, Yu

AU - Sawyers, Charles L

AU - Clevers, Hans C

PY - 2014/9/25

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N2 - 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.

AB - 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.

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VL - 159

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EP - 175

JO - Cell

JF - Cell

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Identification of multipotent luminal progenitor cells in human prostate organoid cultures

Abstract

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