Karthaus Wouter R, Iaquinta Phillip J, Drost Jarno, Gracanin Ana, van Boxtel Ruben, Wongvipat John, Dowling Catherine M, Gao Dong, Begthel Harry, Sachs Norman, Vries Robert G J, Cuppen Edwin, Chen Yu, Sawyers Charles L, Clevers Hans C
Hubrecht Institute, Royal Netherlands Academy of Arts and Sciences and University Medical Center Utrecht, 3584 CT, Utrecht, Netherlands.
Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
Cell. 2014 Sep 25;159(1):163-175. doi: 10.1016/j.cell.2014.08.017. Epub 2014 Sep 4.
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.
前列腺由排列成假复层上皮的基底细胞和管腔细胞组成。在组织重组模型中，只有基底细胞能重建完整的前列腺，但小鼠谱系追踪实验表明，管腔细胞能产生基底细胞。由于缺乏能够重现前列腺结构的培养条件，要阐明这些转变的分子细节以及它们是否适用于人类仍然具有挑战性。在此，我们描述了一种三维培养系统，该系统支持原代小鼠和人类前列腺类器官的长期扩增，这些类器官由完全分化的CK5+基底细胞和CK8+管腔细胞组成。类器官基因稳定，在重组试验中能重建前列腺，并且可以进行实验操作。单个的人类管腔细胞和基底细胞能产生类器官，但管腔细胞来源的类器官更类似于前列腺。这些数据支持前列腺组织的管腔多谱系祖细胞模型，并建立了一个强大的、可扩展的用于机制研究的系统。
