Identification of multipotent luminal progenitor cells in human prostate organoid cultures.
Identification of multipotent luminal progenitor cells in human prostate organoid cultures.
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DOI：
10.1016/j.cell.2014.08.017
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发表时间：
2014-09-25
期刊：
影响因子：
64.5
通讯作者：
Clevers HC
中科院分区：
文献类型：
--
作者：
Karthaus WR;Iaquinta PJ;Drost J;Gracanin A;van Boxtel R;Wongvipat J;Dowling CM;Gao D;Begthel H;Sachs N;Vries RGJ;Cuppen E;Chen Y;Sawyers CL;Clevers HC
前列腺由基细胞和腔细胞组成，排列成假复层上皮。在组织重组模型中，只有基底细胞才能重建完整的前列腺，但小鼠的谱系追踪实验表明，腔细胞产生基底细胞。由于缺乏概括前列腺结构的培养条件，解决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。在这里，我们描述了一种3D培养系统，它支持小鼠和人前列腺器官的长期扩增，由完全分化的CK5+基底细胞和CK8+腔细胞组成。有机化合物在基因上是稳定的，可以在重组试验中重建前列腺体，并且可以进行实验操作。单个人的腔细胞和基底细胞产生有机类化合物，而腔细胞衍生的有机类化合物更类似于前列腺癌。这些数据支持前列腺组织的腔多谱系祖细胞模型，并为机械研究建立了一个强大的、可扩展的系统。
The prostate gland consists of basal and luminal cells arranged as pseudo-stratified 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.