Stem cell and regeneration regulatory genes in planarians

涡虫的干细胞和再生调控基因

• 批准号: 9311346
• 负责人: PETER REDDIEN
• 金额: $ 37.79万
• 依托单位: WHITEHEAD INSTITUTE FOR BIOMEDICAL RES
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-03-20 至 2021-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9311346
• 关键词: Address; Adult; Animals; Area; Biological Models; Biology; Body Regions; Body part; Cell Count; Cell Differentiation process; Cell Proliferation; Cells; Complex; Cues; Data; Databases; Decapitation; Destinations; Eye; Fresh Water; Generic Drugs; Genes; Genetic Transcription; Genetic study; Genome; Goals; Grant; Growth; Head; Health; Heart; Home environment; Human; Human Biology; Human Genome; Injury; Instruction; Lead; Location; Longevity; Maintenance; Malignant Neoplasms; Mesenchymal; Modeling; Molecular; Molecular Genetics; Muscle; Natural regeneration; Nature; Nervous system structure; Organism; Outcome; Pattern; Planarians; Platyhelminths; Population; Process; Production; Property; Public Health; RNA Interference; Regenerative Medicine; Regenerative response; Regulation; Regulator Genes; Signal Transduction; Site; Sorting - Cell Movement; Stem cells; Structure; System; Testing; Tissues; Work; Wound Healing; adult stem cell; aged; blind; cancer type; cell type; eye regeneration; fascinate; human disease; in vivo; insight; interest; mature animal; progenitor; programs; regenerative; response; self-renewal; stem cell biology; stem cell fate specification; tissue repair; tool; transcriptome; transcriptome sequencing; wound

Project Summary Planarian flatworms are famous for their ability to rapidly regenerate new heads or even entire organisms from a tiny fragment of the animal. Planarian regeneration involves a population of proliferative cells (neoblasts) that include pluripotent adult stem cells (cNeoblasts) and that can produce every cell of the adult animal. Despite centuries of fascination with regeneration, mechanistic explanations await elucidation. The broad, long-term objectives of this proposal are to use planarians as a model system to identify and understand the molecular mechanisms that regulate stem cells to promote regeneration. The specific aims are: 1) To determine the mechanism of tissue-specific regeneration, 2) To determine how progenitors organize into a regenerated structure, and 3) To identify in vivo regulatory mechanisms of stem cell fate specification. Stem cells and regenerative biology are the subjects of recent and intense interest for regenerative medicince. In addition, the misregulation of stem cells may be central to many types of cancer. A newly developed arsenal of tools for molecular genetic study of stem cell biology in planarians now exists. For example, systematic gene perturbation with RNA interference (RNAi) is possible and the planarian genome has been sequenced. Greater than half of planarian genes have counterparts in the human genome; therefore, planarian studies should identify conserved stem cell regulatory mechanisms. Aim #1 will determine the mechanisms by which a stem cell response can bring about the specific regeneration of exactly those tissues that were missing. This is a fundamental problem of wound repair and regeneration in most organisms, including humans. Aim #2 will determine the mechanisms that lead regenerative progenitors to incorporate into the correct tissues at the correct locations. We will utilize the study of planarian eye progenitors for this work. These eye progenitors "home" to the exact location where eyes should form, and are incorporated into existing eyes. Aim #3 will study the mechanisms of stem cell fate specification. Some processes must exist to regulate stem cell number in planarians, and their choice to make more stem cells or to make differentiated cells. We will study how contextual cues regulate this process by investigating candidate neoblast regulatory cells and by study of the specialization of planarian stem cells into regenerative progenitors of the nervous system. Successful completion of proposed aims will greatly advance our understanding of the mechanistic basis for regeneration and advance planarians as a model system for the study of genes conserved in humans in stem cell and regenerative biology, areas of great importance in human health.

项目摘要 Planarian扁形虫以其快速再生新头部甚至整个生物体的能力而闻名。 动物的一小部分Planarian再生涉及增殖细胞（neoblasts）群体， 包括多能成体干细胞（cNeoblasts），其可以产生成年动物的每一个细胞。尽管 几个世纪以来人们对再生的迷恋，机械的解释等待着阐明。广泛、长期 这个建议的目的是使用真涡虫作为一个模型系统，以确定和理解分子 调节干细胞以促进再生的机制。具体目标是：1）确定 组织特异性再生的机制，2）为了确定祖细胞如何组织成再生的细胞， 结构，以及3）鉴定干细胞命运特化的体内调节机制。干细胞和 再生生物学是再生医学最近和强烈兴趣的主题。此外该 干细胞的失调可能是许多类型癌症的核心。新开发的工具库， 现在存在对真涡虫干细胞生物学的分子遗传学研究。例如，系统基因 RNA干扰（RNAi）干扰是可能的，并且真涡虫基因组已经测序。更大 超过一半的涡虫基因在人类基因组中有对应物;因此，涡虫研究应该 鉴定保守的干细胞调节机制。目标1将确定股骨柄 细胞反应可以使那些缺失的组织再生。这是一 创伤修复和再生的基本问题在大多数生物体中，包括人类。目标#2将 确定机制，导致再生祖细胞纳入正确的组织在 正确的位置。我们将利用这项工作的研究，涡虫眼祖细胞。这些眼睛祖细胞 “家”的确切位置，眼睛应该形成，并纳入现有的眼睛。目标#3将 研究干细胞命运特化的机制。必须存在一些过程来调节干细胞数量 以及它们选择制造更多的干细胞还是制造分化的细胞。我们将研究如何 背景线索通过研究候选的成新细胞调节细胞和通过研究 这一过程可以使真涡虫干细胞特化为神经系统的再生祖细胞。成功 所提出的目标的完成将极大地促进我们对再生机制基础的理解 和先进的涡虫作为一个模型系统的研究基因保守的人类干细胞和 再生生物学，对人类健康非常重要的领域。