Faubert Amélie, Lessard Julie, Sauvageau Guy
Laboratory of Molecular Genetics of Hematopoietic Stem Cells, Institute of Research in Immunology and Cancer, University of Montreal, Quebec, Canada.
Oncogene. 2004 Sep 20;23(43):7247-55. doi: 10.1038/sj.onc.1207944.
Stem cells have acquired a golden glow in the past few years as they represent possible tools for reversing the damage wreak on organs. These cells are found not only in major regenerative tissues, such as the epithelia, blood and testes, but also in 'static tissues', such as the nervous system and liver, where they play a central role in tissue growth and maintenance. The mechanism by which stem cells maintain populations of highly differentiated, short-lived cells seems to involve a critical balance between alternate fates: daughter cells either maintain stem cell identity or initiate differentiation. Recent studies in lower organisms have unveiled the regulatory mechanisms of asymmetric stem cell divisions. In these models, the surrounding environment likely provides key instructive signals for the cells to choose one fate over another. Our understanding now extends to the intrinsic mechanisms of cell polarity that influence asymmetrical stem cell divisions. This article focuses on the genetic determinants of asymmetric stem cell divisions in lower organisms as a model for studying the process of self-renewal of mammalian hematopoietic stem cells.
在过去几年里,干细胞已获得了耀眼的光环,因为它们代表了逆转器官损伤的可能工具。这些细胞不仅存在于主要的再生组织中,如上皮、血液和睾丸,还存在于“静态组织”中,如神经系统和肝脏,它们在组织生长和维持中发挥着核心作用。干细胞维持高度分化、寿命短暂的细胞群体的机制似乎涉及两种不同命运之间的关键平衡:子细胞要么维持干细胞身份,要么开始分化。最近对低等生物的研究揭示了不对称干细胞分裂的调控机制。在这些模型中,周围环境可能为细胞选择一种命运而非另一种提供关键的指导信号。我们现在对影响不对称干细胞分裂的细胞极性内在机制也有了更深入的了解。本文聚焦于低等生物中不对称干细胞分裂的遗传决定因素,以此作为研究哺乳动物造血干细胞自我更新过程的模型。