Department of Genetics, Washington University Medical School, St Louis, MO 63130, USA.
Development. 2013 Mar;140(5):996-1002. doi: 10.1242/dev.088112. Epub 2013 Jan 30.
Adult stem cells are crucial for growth, homeostasis and repair of adult animals. The melanocyte stem cell (MSC) and melanocyte regeneration is an attractive model for studying regulation of adult stem cells. The process of melanocyte regeneration can be divided into establishment of the MSC, recruitment of the MSC to produce committed daughter cells, and the proliferation, differentiation and survival of these daughter cells. Reduction of Kit signaling results in dose-dependent reduction of melanocytes during larval regeneration. Here, we use clonal analysis techniques to develop assays to distinguish roles for these processes during zebrafish larval melanocyte regeneration. We use these clonal assays to investigate which processes are affected by the reduction in Kit signaling. We show that the regeneration defect in kita mutants is not due to defects in MSC recruitment or in the proliferation, differentiation or survival of the daughter cells, but is instead due to a defect in stem cell establishment. Our analysis suggests that the kit MSC establishment defect results from inappropriate differentiation of the MSC lineage.
成体干细胞对于成年动物的生长、内稳态和修复至关重要。黑素细胞干细胞(MSC)和黑素细胞再生是研究成体干细胞调控的理想模型。黑素细胞再生过程可分为 MSC 的建立、MSC 的募集以产生定向子细胞,以及这些子细胞的增殖、分化和存活。Kit 信号的减少导致幼虫再生过程中黑素细胞的剂量依赖性减少。在这里,我们使用克隆分析技术开发了用于区分斑马鱼幼虫黑素细胞再生过程中这些过程作用的测定方法。我们使用这些克隆测定方法来研究 Kit 信号减少会影响哪些过程。我们表明,kita 突变体的再生缺陷不是由于 MSC 募集或子细胞的增殖、分化或存活缺陷引起的,而是由于干细胞建立缺陷引起的。我们的分析表明,kit MSC 建立缺陷是由于 MSC 谱系的不当分化所致。