Howard Hughes Medical Institute, Department of Developmental Biology, Stanford University, School of Medicine, Stanford, CA 94305-5323, USA.
Cell Stem Cell. 2010 Jun 4;6(6):568-77. doi: 10.1016/j.stem.2010.03.020.
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.
成体干细胞具有自我更新和产生特化细胞的能力。自我更新依赖于外在的生态位因素，但目前只鉴定到少数几种信号。此外，干细胞在缺乏适当信号时往往会分化，因此在细胞培养中很难维持。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，起源于干细胞，并且很容易从移植细胞中产生。我们在此表明，成年乳腺中含有对 Wnt 反应的细胞群体，该群体富含干细胞。此外，对负反馈调节剂 Axin2 突变的干细胞（因此对 Wnt 信号敏感）在乳腺重建测定中具有竞争优势。在细胞培养实验中，纯化的 Wnt 蛋白可使乳腺干细胞克隆性扩增多代，并保持其在移植测定中生成功能性腺体的能力。我们得出结论，Wnt 蛋白作为限速的自我更新信号，直接作用于乳腺干细胞。
