Pituitary Progenitor Cells Tracked Down by Side Population Dissection

Pituitary Progenitor Cells Tracked Down by Side Population Dissection
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DOI:
10.1002/stem.51
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发表时间:
2009-01-01
期刊:
影响因子:
5.2
通讯作者:
Vankelecom, Hugo
Vankelecom, Hugo
中科院分区:
医学2区
文献类型:
--
作者:
Chen, Jianghai;Gremeaux, Lies;Vankelecom, Hugo

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SP内的Sca1(高)亚群,即诱导SP扩增的干细胞生长因子,影响胚胎因子的转录,表明对SP室内展开的发育程序有影响。Sox2表达显示,非sca1(高)SP细胞存在于假定的腔周围干/祖细胞壁龛中,但也存在于分散在腺体中的小群体中,从而支持存在多个壁龛。在经历垂体生长波的早期产后小鼠中,Sox2 - 1细胞比成年小鼠更丰富,与较大的SP和较高的非sca1(高)比例一致。总之,我们通过SP表型追踪垂体祖细胞,从而提供了一种简单的方法来分离和检查这些细胞从体外的塑性垂体,以及一个培养系统来深入探索其调控网络。干细胞2009;[07:11 . 82]脑下垂体是内分泌的核心,通过调整其细胞组成来适应不断变化的需求,从而控制身体的荷尔蒙状况。据推测,干细胞/祖细胞参与了这种重塑。最近,我们在垂体前叶发现了一个候选干细胞/祖细胞群。在这里,我们仔细检查了这个“侧群”(SP),并显示,出乎意料的是,不是表达高水平“干细胞抗原-1”的亚群(Sca1(高)),而是其余的非Sca1(高)部分聚集垂体祖细胞。转录组调查显示,在非鳞状细胞1(高)SP中,垂体干/祖细胞标记物Sox2和Sox9的表达上调,以及垂体胚胎发生的多个关键因素的表达上调。非sca1(高)SP包围了产生球体并显示多能激素分化能力的细胞。在培养条件下选择非
Sca1(high) subset within the SP, stem cell growth factors that induce SP expansion, affect transcription of embryonic factors, suggesting impact on a developmental program that unfolds within this SP compartment. Non-Sca1(high) SP cells, revealed by Sox2 expression, are observed in the postulated periluminal stem/progenitor cell niche, but also in small groups scattered over the gland, thereby advocating the existence of multiple niches. In early postnatal mice undergoing a pituitary growth wave, Sox2 1 cells are more abundant than in adults, concordant with a larger SP and higher non-Sca1(high) proportion. Together, we tracked down pituitary progenitor cells by SP phenotype, and thus provide a straightforward method to isolate and scrutinize these cells from the plastic pituitary ex vivo, as well as a culture system for in-depth exploration of their regulatory network. STEM CELLS 2009;27:1182-1195The pituitary gland represents the endocrine core, governing the body's hormonal landscape by adapting its cellular composition to changing demands. It is assumed that stem/progenitor cells are involved in this remodeling. Recently, we uncovered a candidate stem/progenitor cell population in the anterior pituitary. Here, we scrutinized this "side population'' ( SP) and show that, unexpectedly, not the subset expressing high levels of "stem cell antigen-1'' ( Sca1(high)) but the remainder non-Sca1(high) fraction clusters the pituitary progenitor cells. Transcriptomal interrogation revealed in the non-Sca1(high) SP upregulated expression of the pituitary stem/progenitor cell markers Sox2 and Sox9, and of multiple factors critically involved in pituitary embryogenesis. The non-Sca1(high) SP encloses the cells that generate spheres and display multipotent hormone differentiation capacity. In culture conditions selecting for the non-