Stem cell proliferation and differentiation in planaria

涡虫干细胞增殖和分化

• 批准号: 6570356
• 负责人: Phillip A Newmark
• 金额: $ 26.9万
• 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 2007-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6570356
• 关键词: Platyhelminthes; blastema; cell cycle; cell differentiation; cell growth regulation; cell population study; cell proliferation; cell type; complementary DNA; developmental genetics; double stranded RNA; genetic screening; in situ hybridization; monoclonal antibody; pluripotent stem cells; regeneration; stem cells

DESCRIPTION (provided by applicant): The establishment of human pluripotential stem 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, Schmidt Mediterranean, 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 analyzing cell cycle kinetics in intact and regenerating planarians. These experiments will determine 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 understanding the signaling pathways that lead from wounding to proliferation. The development of automated in situ hybridization techniques and the availability 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 interference will be used to identify genes that play critical roles in stern cell regulation.

描述（由申请人提供）：人类多能干细胞系的建立导致了对干细胞生物学的兴趣的复苏。这种兴趣主要是由于干细胞修复退行性疾病和损伤的治疗潜力。在人类干细胞研究的最新突破可以有效和安全地应用于临床之前，需要解决有关干细胞生物学的许多基本问题。其中包括：如何在体内调节干细胞增殖以产生适当数量的子代干细胞和分化后代而不形成肿瘤？干细胞的发育潜能是如何被限制在特定的命运中的？如何维持多能性，哪些步骤会导致多能性丧失？这里提出的工作将解决这些基本问题，使用淡水涡虫，施密特地中海，作为研究干细胞调节的模式生物。Planarians-再生实验的经典模型可以从身体的小碎片再生整个动物。这种显著的可塑性是基于成虫中存在的干细胞群。这些干细胞既用于替换细胞更替过程中丢失的细胞，又用于在动物被横切时再生缺失的结构。最近的进展允许这个经典的系统在细胞和分子水平上进行详细的重新检查。因此，环境对干细胞增殖的影响将通过分析完整和再生的涡虫细胞周期动力学来研究。这些实验将确定创伤是否调节了涡虫干细胞的细胞周期。如果是这样，这些实验还将确定受调节的细胞周期阶段，这是理解从创伤到增殖的信号通路的重要考虑因素。自动化原位杂交技术的发展和超过4000个独特的真涡虫cDNA的可用性为定义干细胞特异性基因和产生单克隆抗体以识别和研究干细胞提供了起始材料。最后，使用双链RNA介导的遗传干扰的功能分析将用于识别在干细胞调控中发挥关键作用的基因。