Stem cell proliferation and differentiation in planaria

人类多潜能干细胞系的建立重新引起了人们对 干细胞生物学。这种兴趣很大程度上归功于干细胞修复的治疗潜力。 退行性疾病和损伤。在人类干细胞研究取得最新突破之前 将干细胞生物学的许多基本问题有效、安全地应用于临床 需要解决的问题。这些包括：干细胞增殖是如何在体内受到调节的，以产生 适当数量的子代干细胞和分化的后代而不会形成肿瘤？多么 干细胞的发展潜力是否受到特定命运的限制？多潜能是怎样的？ 维持和采取哪些步骤会导致丧失多潜能？这里提出的工作将解决 这些基本问题是以淡水浮游生物Schmic/Tea Medterranea为模型的 研究干细胞调节的有机体。行星动物-再生实验的经典模型- 可以从动物身体的小碎片中再生出完整的动物。这种非凡的可塑性是 基于成虫体内的干细胞群。这些干细胞被用来 替换在细胞周转过程中丢失的细胞，并在 动物被横切。最近的进展使这一经典系统能够在 细胞和分子水平。因此，将研究环境对干细胞增殖的影响。 通过分析完整和再生的浮游生物的细胞周期动力学。这些实验将阻止- 我的如果受伤了，就会调节脊椎动物干细胞的细胞周期。如果是这样的话，这些实验将 还定义了细胞周期中受调控的阶段，这是理解- 激活从损伤到增殖的信号通路。自动化技术的发展 原位杂交技术和4000多种独特的浮游生物cDNA的可用性提供了 定义干细胞特异性基因和提高单抗鉴定的起始材料 研究干细胞。最后，利用双链RNA介导的遗传交互作用进行功能分析。 费伦斯将被用于识别在严格的细胞调控中发挥关键作用的基因。

The establishment of human pluripotential stem cell cell lines has led to a resurgence of interest in stem cell biology. This interest is largely due to the therapeutic potential of stem cells for repairing degenerative diseases and injuries. Before recent breakthroughs in studies of human stem cells can be effectively and safely applied in the clinic, many basic questions about the biology of stem cells need to be addressed. These include: how is stem cell proliferation regulated in vivo to generate the appropriate number of daughter stem cells and differentiating progeny without forming tumors? How is the developmental potential of a stem cell restricted to a particular fate? How is pluripotentiality maintained and what steps lead to loss of pluripotentiality? The work proposed here will address these fundamental questions using the freshwater planarian, Schmic/tea mediterranea, as a model organism for studying stem cell regulation. Planarians- classic models of regeneration experiments- can regenerate entire animals from small fragments of their bodies. This remarkable plasticity is based upon a stem cell population present in the adult worm. These stem cells are used both to replace cells lost during the course of cell turnover and to regenerate missing structures when the animal is transected. Recent advances permit this classic system to be re-examined in detail at both cellular and molecular levels. Thus, environmental influences on stem cell proliferation will be studied by analysing cell cycle kinetics in intact and regeneratiing planarians. These experiments will deter- mine if wounding regulates the cell cycle of planarian stem cells. If it does, these experiments will also define the phases of the cell cycle that are regulated, an important consideration for understand- ing the signaling pathways that lead from wounding to proliferation. The development of automated in situ hybridization techniques and the availablility of over 4000 unique planarian cDNAs provide starting material for defining stem cell-specific genes and raising monoclonal antibodies to identify and study stem cells. Finally, functional analysis using double-stranded RNA-mediated genetic inter- ference will be used to identify genes that play critical roles in stern cell regulation.