Mechanisms of Organ Regeneration in the planarian Schmidtea mediterranea

涡虫 Schmidtea mediterranea 的器官再生机制

• 批准号: 7485945
• 负责人: Carolyn Elizabeth Adler
• 金额: $ 4.68万
• 依托单位: UNIVERSITY OF UTAH
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-04-01 至 2009-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7485945
• 关键词: Amputation; Animal Feed; Animals; Antibodies; Biological Assay; Bromodeoxyuridine; Candidate Disease Gene; Cell Cycle; Cell Cycle Kinetics; Cell division; Cells; Cellular biology; Development; Disease; Excision; Flow Cytometry; Gene Library; Genes; Genome; Goals; Human; In Situ; Injury; Label; Life; Microarray Analysis; Molecular; Natural regeneration; Organ; Pathway interactions; Pattern; Pharyngeal structure; Phenotype; Planarians; Population; Process; RNA Interference; Regenerative Medicine; Research; Role; Signal Pathway; Signal Transduction; Staining method; Stains; Stem cells; Techniques; Tissues; Toxin; Trauma; Wound Healing; cell behavior; day; experience; knock-down; mature animal; member; notch protein; organ regeneration; pathogen; repaired; research study; response

DESCRIPTION (provided by applicant): All animals experience tissue injury from toxins, pathogens and bodily trauma throughout their lives. Repair and renewal of damaged tissues is essential, but we know little about this process at the molecular level, and understanding it is critical for the development of regenerative medicine. One common mechanism of tissue repair relies upon activation of stem cells to produce new tissue lost during injury. I will investigate the mechanisms controlling stem-cell-driven organ regeneration in the planarian Schmidtea mediterranea, an animal with a remarkable capacity for regrowth and a highly accessible stem cell population. I will focus on the pharynx, which can be selectively amputated and completely regenerates within ten days. My first goal is to define the cellular response to amputation and regeneration using BrdU incorporation and cell cycle analysis. Microarray analysis of animals undergoing pharynx regeneration will identify genes that are differentially regulated during this process. To uncover additional genes required for pharynx regeneration, I will couple a large-scale RNA interference (RNAi) screen of planarian cDNAs with pharynx amputation. Morphological, functional and anatomical phenotypes of RNAi-fed animals will identify putative candidate genes. For candidate regeneration genes, I will determine expression patterns during regeneration and characterize the anatomical and cellular phenotypes caused by gene knockdown. I will also determine whether candidate genes act specifically to recognize the absence of a pharynx. Together, these experiments will identify the molecular pathways involved in the assembly of new organs in adult animals. Relevance The research in this proposal explores how stem cells in adult animals are able to regenerate an entire organ after its removal. The experiments focus on planarians, animals that can regenerate every organ and have extremely accessible stem cells. Because stem cells are often activated during human injuries, these studies will contribute to our understanding of regenerative medicine and stem cell biology.

描述（由申请人提供）：所有动物一生都会经历毒素、病原体和身体创伤造成的组织损伤。受损组织的修复和更新至关重要，但我们在分子水平上对这一过程知之甚少，了解它对于再生医学的发展至关重要。组织修复的一种常见机制依赖于干细胞的激活以产生损伤期间丢失的新组织。我将研究地中海真涡虫中干细胞驱动的器官再生的控制机制，这种动物具有非凡的再生能力和易于获取的干细胞群。我将重点关注咽部，它可以选择性截肢并在十天内完全再生。我的第一个目标是使用 BrdU 掺入和细胞周期分析来定义细胞对截肢和再生的反应。对经历咽再生的动物进行微阵列分析将识别在此过程中受到差异调节的基因。为了发现咽部再生所需的其他基因，我将把涡虫 cDNA 的大规模 RNA 干扰 (RNAi) 筛选与咽部截肢结合起来。 RNAi 喂养动物的形态、功能和解剖表型将鉴定假定的候选基因。对于候选再生基因，我将确定再生过程中的表达模式，并表征由基因敲低引起的解剖和细胞表型。我还将确定候选基因是否专门用于识别咽部的缺失。这些实验将共同确定成年动物新器官组装所涉及的分子途径。相关性 本提案中的研究探讨了成年动物的干细胞如何能够在切除后再生整个器官。实验的重点是涡虫，这种动物可以再生每个器官，并且拥有极其容易获得的干细胞。由于干细胞经常在人体受伤时被激活，这些研究将有助于我们对再生医学和干细胞生物学的理解。