Chen Jianghai, Gremeaux Lies, Fu Qiuli, Liekens Daisy, Van Laere Steven, Vankelecom Hugo
Department of Molecular Cell Biology, Laboratory of Tissue Plasticity, University of Leuven (KU Leuven), Leuven, Belgium.
Stem Cells. 2009 May;27(5):1182-95. doi: 10.1002/stem.51.
The 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-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(+) 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.
垂体是内分泌核心，通过调整细胞组成以适应不断变化的需求来调控人体的激素环境。一般认为，干/祖细胞参与了这一重塑过程。最近，我们在前叶垂体中发现了一个候选干/祖细胞群体。在此，我们仔细研究了这个“侧群”（SP），结果意外地发现，并非表达高水平“干细胞抗原-1”（Sca1(高)）的亚群，而是其余非Sca1(高)部分聚集了垂体祖细胞。转录组分析显示，在非Sca1(高)的SP中，垂体干/祖细胞标志物Sox2和Sox9以及多个在垂体胚胎发生中起关键作用的因子表达上调。非Sca1(高)的SP包含能够形成球体并具有多能激素分化能力的细胞。在选择SP中非Sca1(高)亚群的培养条件下，诱导SP扩增的干细胞生长因子会影响胚胎因子的转录，这表明其对在该SP区室中展开的发育程序有影响。通过Sox2表达揭示的非Sca1(高)SP细胞，不仅在假定的管周干/祖细胞龛中被观察到，也在腺体中散在分布的小群体中被观察到，这表明存在多个龛。在经历垂体生长高峰期的新生小鼠早期，Sox2(+)细胞比成年小鼠中更为丰富，这与更大的SP和更高的非Sca1(高)比例相一致。总之，我们通过SP表型追踪到了垂体祖细胞，从而提供了一种直接的方法来从可塑性垂体中离体分离和研究这些细胞，以及一个用于深入探索其调控网络的培养系统。
