Zhang Ying V, Cheong Janice, Ciapurin Nichita, McDermitt David J, Tumbar Tudorita
Department of Molecular Biology and Genetics, Cornell University, Ithaca, NY 14853, USA.
Cell Stem Cell. 2009 Sep 4;5(3):267-78. doi: 10.1016/j.stem.2009.06.004. Epub 2009 Aug 6.
In homeostasis of adult vertebrate tissues, stem cells are thought to self-renew by infrequent and asymmetric divisions that generate another stem cell daughter and a progenitor daughter cell committed to differentiate. This model is based largely on in vivo invertebrate or in vitro mammal studies. Here, we examine the dynamic behavior of adult hair follicle stem cells in their normal setting by employing mice with repressible H2B-GFP expression to track cell divisions and Cre-inducible mice to perform long-term single-cell lineage tracing. We provide direct evidence for the infrequent stem cell division model in intact tissue. Moreover, we find that differentiation of progenitor cells occurs at different times and tissue locations than self-renewal of stem cells. Distinct fates of differentiation or self-renewal are assigned to individual cells in a temporal-spatial manner. We propose that large clusters of tissue stem cells behave as populations whose maintenance involves unidirectional daughter-cell-fate decisions.
在成年脊椎动物组织的稳态中，干细胞被认为通过不频繁且不对称的分裂进行自我更新，这种分裂产生另一个干细胞子代和一个致力于分化的祖细胞子代。该模型主要基于体内无脊椎动物或体外哺乳动物研究。在此，我们通过使用具有可抑制的H2B - GFP表达的小鼠来追踪细胞分裂，并利用Cre诱导型小鼠进行长期单细胞谱系追踪，来研究成年毛囊干细胞在其正常环境中的动态行为。我们为完整组织中不频繁的干细胞分裂模型提供了直接证据。此外，我们发现祖细胞的分化发生在与干细胞自我更新不同的时间和组织位置。分化或自我更新的不同命运以时空方式分配给单个细胞。我们提出，大量的组织干细胞群表现为一个群体，其维持涉及单向的子细胞命运决定。
