Stem cell proliferation and differentiation in planaria

涡虫干细胞增殖和分化

• 批准号: 7160539
• 负责人: Phillip A Newmark
• 金额: $ 25.43万
• 依托单位: UNIVERSITY OF ILLINOIS AT URBANA-CHAMPAIGN
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-01-09 至 2009-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7160539
• 关键词: Address; Adult; Amputation; Animal Model; Animals; Antibodies; Behavior; Biology; Cell Cycle; Cell Cycle Kinetics; Cell Line; Cell Proliferation; Cells; Cellular biology; Clinic; Daughter; Degenerative Disorder; Development; Double-Stranded RNA; Epithelium; Equilibrium; Expressed Sequence Tags; Failure; Fresh Water; Generations; Genes; Genetic; Goals; Human; In Situ Hybridization; Individual; Injury; Knowledge; Lead; Mediating; Mining; Mitotic; Modeling; Molecular; Monoclonal Antibodies; Natural regeneration; Numbers; Pathway interactions; Phase; Physiological; Planarians; Platyhelminths; Play; Population; Process; Proteins; Regulation; Role; Screening procedure; Signal Pathway; Signal Transduction; Stem cells; Structure; System; Tea; Techniques; Therapeutic; Tissues; Whole Organism; Work; base; blastema; cell type; human stem cells; in vivo; injured; insight; interest; migration; repaired; research study; response; stem; tumor; wound

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.

人类多能干细胞系的建立重新引起了人们的兴趣 干细胞生物学。这种兴趣很大程度上是由于干细胞修复的治疗潜力 退行性疾病和损伤。在最近人类干细胞研究取得突破之前 为了有效、安全地应用于临床，有关干细胞生物学的许多基本问题 需要解决。其中包括：干细胞增殖如何在体内调节以产生 适当数量的子代干细胞并分化后代而不形成肿瘤？如何 干细胞的发育潜力是否受限于特定的命运？多能性如何 维持以及哪些步骤会导致多能性丧失？这里提出的工作将解决 使用淡水涡虫 Schmic/tea mediterranea 作为模型来解决这些基本问题 用于研究干细胞调节的生物体。涡虫-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 基于成虫中存在的干细胞群。这些干细胞用于 替换细胞更替过程中丢失的细胞，并在细胞死亡时再生丢失的结构 动物被横断。最近的进展使得这个经典系统可以在两个方面进行详细的重新检查 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涡虫的细胞周期动力学。这些实验将阻止—— 如果受伤能调节涡虫干细胞的细胞周期，我的观点是这样的。如果确实如此，这些实验将 还定义了受调节的细胞周期阶段，这是理解的重要考虑因素- 导致从受伤到增殖的信号通路。自动化的发展 原位杂交技术和 4000 多种独特的涡虫 cDNA 提供了 用于定义干细胞特异性基因并产生单克隆抗体以识别的起始材料 并研究干细胞。最后，使用双链RNA介导的遗传间功能分析 参考将用于识别在干细胞调节中发挥关键作用的基因。