Wnt Proteins Are Self-Renewal Factors for Mammary Stem Cells and Promote Their Long-Term Expansion in Culture
Wnt Proteins Are Self-Renewal Factors for Mammary Stem Cells and Promote Their Long-Term Expansion in Culture
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DOI：
10.1016/j.stem.2010.03.020
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发表时间：
2010-06-04
期刊：
影响因子：
23.9
通讯作者：
Nusse, Roel
中科院分区：
文献类型：
--
作者：
Zeng, Yi Arial;Nusse, Roel
成体干细胞具有自我更新和产生特化细胞的能力。自我更新依赖于外部的利基因素，但这些信号中很少有人被识别出来。此外，干细胞往往在缺乏适当信号的情况下分化，因此很难在细胞培养中保持。乳腺为研究自我更新信号提供了一个极好的系统，因为该器官在出生后发育，由干细胞产生，并很容易从移植细胞产生。我们在这里显示，成人乳腺包含一个Wnt反应细胞群，该细胞群富含干细胞。此外，突变为负反馈调节器Axin2的干细胞因此对Wnt信号敏感，在乳腺重建试验中具有竞争优势。在细胞培养实验中，接触纯化的Wnt蛋白可克隆扩增多代乳腺干细胞，并在移植试验中保持其生成功能性腺体的能力。我们得出结论，Wnt蛋白是直接作用于乳腺干细胞的限速自我更新信号。
Adult stem cells have the ability to self-renew and to generate specialized cells. Self-renewal is dependent on extrinsic niche factors but few of those signals have been identified. In addition, stem cells tend to differentiate in the absence of the proper signals and are therefore difficult to maintain in cell culture. The mammary gland provides an excellent system to study self-renewal signals, because the organ develops postnatally, arises from stem cells, and is readily generated from transplanted cells. We show here that adult mammary glands contain a Wnt-responsive cell population that is enriched for stem cells. In addition, stem cells mutant for the negative-feedback regulator Axin2 and therefore sensitized to Wnt signals have a competitive advantage in mammary gland reconstitution assays. In cell culture experiments, exposure to purified Wnt protein clonally expands mammary stem cells for many generations and maintains their ability to generate functional glands in transplantation assays. We conclude that Wnt proteins serve as rate-limiting self-renewal signals acting directly on mammary stem cells.