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

Research output: Contribution to journal/periodicalArticleScientificpeer-review

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 languageEnglish
Pages (from-to)163-75
Number of pages13
JournalCell
Volume159
Issue number1
DOIs
Publication statusPublished - 25 Sep 2014

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