The adult pituitary contains a cell population displaying stem/progenitor cell and early embryonic characteristics
The adult pituitary contains a cell population displaying stem/progenitor cell and early embryonic characteristics
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DOI：
10.1210/en.2005-0185
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发表时间：
2005-09-01
期刊：
影响因子：
4.8
通讯作者：
Vankelecom, H
中科院分区：
文献类型：
--
作者：
Chen, JH;Hersmus, N;Vankelecom, H
在许多组织中已经发现了一个侧群(SP)，在这些组织中，它通常代表一个富含干细胞/祖细胞的小种群。在本研究中，我们发现成年小鼠的脑垂体前叶(AP)也含有显示维拉帕米敏感的Hoechst染料外排能力的特征SP。大多数SP细胞高水平表达干细胞抗原1(Sca1(High))。使用(半)定量RT-PCR和免疫荧光技术，我们将Sca1High SP鉴定为富含表达干/祖细胞相关因子和Notch、Wnt和Sonic Hedgehog信号通路组件的细胞群，这些信号通路在干细胞动态平衡和早期垂体胚胎发生中发挥作用。Lhx4是AP早期胚胎发育的关键转录因子，仅在Sca1(高)SP中表达，而Lhx3仅在主要群体中表达，而Lhx4在AP发育后没有下调。Sca1(高)SP从表达分化的AP细胞(激素)表型标志物的细胞中消失，但含有一小部分滤泡星状细胞。在培养过程中，许多组织的干细胞可以克隆性地扩增成非贴壁球体。在AP细胞培养中也可形成克隆球体。球体表现出与Sca1高SP细胞相似的表达模式。此外，垂体球的起始细胞与SP分离，而不与主要群体分离。综上所述，我们发现成年垂体腺含有迄今未描述的具有SP表型和克隆性扩增能力的细胞群。这些细胞表达(信号)分子，通常在干细胞/祖细胞和/或在脑垂体早期胚胎发育过程中起作用。这些特征支持干/祖细胞表型。
A side population (SP) has been identified in a number of tissues, where it typically represents a small population enriched in stem/progenitor cells. In this study we show that the adult mouse anterior pituitary (AP) also contains a characteristic SP displaying verapamil-sensitive Hoechst dye efflux capacity. A majority of the SP cells express stem cell antigen 1 at a high level (Sca1(high)). Using (semi)quantitative RT-PCR and immunofluorescence, we characterized the Sca1high SP as a population enriched in cells expressing stem/progenitor cell-associated factors and components of the Notch, Wnt, and sonic hedgehog signaling pathways, functional in stem cell homeostasis as well as in early pituitary embryogenesis. Lhx4, a transcription factor pivotal for early embryonic development of the AP, was only detected in the Sca1(high) SP, whereas Lhx3, in contrast to Lhx4 not down-regulated after AP development, was only found in the main population. The Sca1(high) SP was depleted from cells expressing phenotypic markers of differentiated AP cells ( hormones), but contained a small proportion of folliculo-stellate cells. Stem cells of many tissues can clonally expand to nonadherent spheres in culture. Clonal spheres also developed in AP cell cultures. Spheres showed an expression pattern resembling that of Sca1high SP cells. Moreover, the sphere-initiating cells of the pituitary segregated to the SP and not to the main population. In conclusion, we show that the adult pituitary contains a hitherto undescribed population of cells with SP phenotype and clonal expansion capacity. These cells express ( signaling) molecules generally found in stem/progenitor cells and/or operative during pituitary early embryonic development. These characteristics are supportive of a stem/progenitor cell phenotype.