Cinquin Olivier
Howard Hughes Medical Institute and Department of Biochemistry, University of Wisconsin-Madison, WI 53706, USA.
J Pathol. 2009 Jan;217(2):186-98. doi: 10.1002/path.2481.
Stem cells are expected to play a key role in the development and maintenance of organisms, and hold great therapeutic promises. However, a number of questions must be answered to achieve an understanding of stem cells and put them to use. Here I review some of these questions, and how they relate to the model system provided by the Caenorhabditis elegans germ line, which is exceptional in its thorough genetic characterization and experimental accessibility under in vivo conditions. A fundamental question is how to define a stem cell; different definitions can be adopted that capture different features of interest. In the C. elegans germ line, stem cells can be defined by cell lineage or by cell commitment ('commitment' must itself be carefully defined). These definitions are associated with two other important questions about stem cells: their functions (which must be addressed following a systems approach, based on an evolutionary perspective) and their regulation. I review possible functions and their evolutionary groundings, including genome maintenance and powerful regulation of cell proliferation and differentiation, and possible regulatory mechanisms, including asymmetrical division and control of transit amplification by a developmental timer. I draw parallels between Drosophila and C. elegans germline stem cells; such parallels raise intriguing questions about Drosophila stem cells. I conclude by showing that the C. elegans germ line bears similarities with a number of other stem cell systems, which underscores its relevance to the understanding of stem cells.
干细胞有望在生物体的发育和维持中发挥关键作用，并具有巨大的治疗前景。然而，要了解干细胞并加以利用，还必须回答一些问题。在此，我将回顾其中一些问题，以及它们与秀丽隐杆线虫生殖系所提供的模型系统之间的关系，该模型系统在其全面的遗传特征和体内条件下的实验可及性方面具有独特之处。一个基本问题是如何定义干细胞；可以采用不同的定义来捕捉不同的感兴趣特征。在秀丽隐杆线虫生殖系中，干细胞可以通过细胞谱系或细胞命运决定（“命运决定”本身必须仔细定义）来定义。这些定义与关于干细胞的另外两个重要问题相关：它们的功能（必须基于进化视角，采用系统方法来探讨）以及它们的调控。我将回顾可能的功能及其进化基础，包括基因组维持以及对细胞增殖和分化的有力调控，以及可能的调控机制，包括不对称分裂和由发育定时器对过渡扩增的控制。我将比较果蝇和秀丽隐杆线虫生殖系干细胞；这种比较对果蝇干细胞提出了有趣的问题。最后我指出，秀丽隐杆线虫生殖系与许多其他干细胞系统具有相似之处，这凸显了它对于理解干细胞的相关性。
