Identification of Multipotent Luminal Progenitor Cells in Human Prostate Organoid Cultures
| Autor: | Charles L. Sawyers, Norman Sachs, Ruben van Boxtel, Jarno Drost, Catherine Dowling, Harry Begthel, Phillip J. Iaquinta, Ana Gracanin, Robert G.J. Vries, Edwin Cuppen, Hans Clevers, Yu Chen, Dong Gao, Wouter R. Karthaus, John Wongvipat |
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| Přispěvatelé: | Hubrecht Institute for Developmental Biology and Stem Cell Research |
| Rok vydání: | 2014 |
| Předmět: |
Male
Biochemistry Genetics and Molecular Biology(all) Stem Cells Tissue Recombination Prostate Biology General Biochemistry Genetics and Molecular Biology Epithelium Human prostate Article Cell biology Organoids Basal (phylogenetics) medicine.anatomical_structure Organ Culture Techniques Immunology medicine Organoid Androgens Humans Stem cell Progenitor cell |
| Zdroj: | Cell, 159(1), 163-75. Elsevier B.V. |
| ISSN: | 0092-8674 |
| DOI: | 10.1016/j.cell.2014.08.017 |
| Popis: | SummaryThe 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. |
| Databáze: | OpenAIRE |
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