Reynolds Susan D, Zemke Anna C, Giangreco Adam, Brockway Brian L, Teisanu Roxana M, Drake Jeffrey A, Mariani Thomas, Di Peter Y P, Taketo Mark M, Stripp Barry R
Center for Lung Regeneration, Department of Environmental and Occupational Health, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
Stem Cells. 2008 May;26(5):1337-46. doi: 10.1634/stemcells.2008-0053. Epub 2008 Mar 20.
Maintenance of classic stem cell hierarchies is dependent upon stem cell self-renewal mediated in part by Wnt/beta-catenin regulation of the cell cycle. This function is critical in rapidly renewing tissues due to the obligate role played by the tissue stem cell. However, the stem cell hierarchy responsible for maintenance of the conducting airway epithelium is distinct from classic stem cell hierarchies. The epithelium of conducting airways is maintained by transit-amplifying cells in the steady state; rare bronchiolar stem cells are activated to participate in epithelial repair only following depletion of transit-amplifying cells. Here, we investigate how signaling through beta-catenin affects establishment and maintenance of the stem cell hierarchy within the slowly renewing epithelium of the lung. Conditional potentiation of beta-catenin signaling in the embryonic lung results in amplification of airway stem cells through attenuated differentiation rather than augmented proliferation. Our data demonstrate that the differentiation-modulating activities of stabilized beta-catenin account for expansion of tissue stem cells.
经典干细胞层级结构的维持依赖于干细胞自我更新，而这部分是由细胞周期的Wnt/β-连环蛋白调控介导的。由于组织干细胞所起的关键作用，该功能在快速更新的组织中至关重要。然而，负责维持传导气道上皮的干细胞层级结构与经典干细胞层级结构不同。在稳态下，传导气道的上皮由过渡扩增细胞维持；只有在过渡扩增细胞耗竭后，罕见的细支气管干细胞才会被激活以参与上皮修复。在此，我们研究通过β-连环蛋白的信号传导如何影响肺缓慢更新上皮内干细胞层级结构的建立和维持。胚胎肺中β-连环蛋白信号的条件性增强通过减弱分化而非增加增殖导致气道干细胞扩增。我们的数据表明，稳定的β-连环蛋白的分化调节活性导致组织干细胞的扩增。
