Self-renewal and multilineage differentiation in vitro from murine prostate stem cells
Self-renewal and multilineage differentiation in vitro from murine prostate stem cells
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DOI：
10.1634/stemcells.2007-0355
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发表时间：
2007-11-01
期刊：
影响因子：
5.2
通讯作者：
Witte, Owen N.
中科院分区：
文献类型：
--
作者：
Xin, Li;Lukacs, Rita U.;Witte, Owen N.
鼠前列腺干细胞表达整合素α 6，其通过与细胞外蛋白层粘连蛋白的相互作用调节存活、增殖和分化信号传导。当在含有层粘连蛋白的Matrigel培养基中体外铺板时，500- 1，000个鼠前列腺细胞中的1个可以生长并形成我们称为前列腺球的克隆形成球状体结构。前列腺球可以单独或批量连续传代，以产生具有相似组成的子代球，表明球形成细胞能够自我更新。球体自发地经历基础和过渡放大细胞类型的谱系特化。位于前列腺球体外层的P63表达细胞具有更高的自我更新能力，而朝向中心的细胞显示出更分化的transit-amplifying表型，如前列腺干细胞抗原的表达所示。当双氢睾酮被添加到培养基中时，雄激素受体被稳定，被输入到细胞核，并驱动分化为管腔细胞样表型。返回到体内环境的一部分球形细胞可以经历分化和形态发生以形成具有伴随前列腺分泌物的限定的基底层和管腔层的前列腺管状结构。本研究证明了在特定的体外微环境中单个成年前列腺干/祖细胞的自我更新和多谱系分化。
Murine prostate stem cells express integrin alpha 6, which modulates survival, proliferation, and differentiation signaling through its interaction with the extracellular protein laminin. When plated in vitro in laminin containing Matrigel medium, 1 of 500-1,000 murine prostate cells can grow and form clonogenic spheroid structures that we term prostate spheres. Prostate spheres can be serially passaged individually or in bulk to generate daughter spheres with similar composition, demonstrating that sphere-forming cells are capable of self-renewal. Spheres spontaneously undergo lineage specification for basal and transit-amplifying cell types. P63-expressing cells localized to the outer layers of prostate spheres possess higher self-renewal capacity, whereas cells toward the center display a more differentiated transit-amplifying phenotype, as demonstrated by the expression of the prostate stem cell antigen. When dihydrotestosterone is added to the medium, the androgen receptor is stabilized, is imported to the nucleus, and drives differentiation to a luminal cell-like phenotype. A fraction of sphere cells returned to an in vivo environment can undergo differentiation and morphogenesis to form prostate tubular structures with defined basal and luminal layers accompanied by prostatic secretions. This study demonstrates self-renewal and multilineage differentiation from single adult prostate stem/progenitor cells in a specific in vitro microenvironment.