Cell signaling in regeneration and tissue scaling

再生和组织缩放中的细胞信号传导

• 批准号: 9893004
• 负责人: Christian Petersen
• 金额: $ 29.35万
• 依托单位: NORTHWESTERN UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-04-01 至 2023-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9893004
• 关键词: Address; Adult; Amputation; Animals; Anterior; Biological; Biological Assay; Competence; Complex; Cues; Data; Detection; Development; Developmental Process; Disease; Dorsal; Expression Profiling; Failure; Foundations; Goals; Grant; Growth; Head; Histologic; Homeostasis; Injury; Length; Link; Location; Maintenance; Medial; Methods; Molecular; Muscle Cells; Natural regeneration; Nature; Operative Surgical Procedures; Organ; Organism; Pathway interactions; Pattern; Planarians; Positioning Attribute; Process; Publishing; RNA Interference; Regulatory Pathway; Role; Signal Pathway; Signal Transduction; Signaling Molecule; System; Testing; Tissue Differentiation; Tissues; base; experience; experimental study; information model; injury and repair; insight; intercellular communication; novel; novel strategies; organ regeneration; progenitor; regenerative; repaired; restoration; stem cells; tissue regeneration; tissue repair; tissue stem cells; transcriptome sequencing

Project Summary/Abstract Organisms with regenerative abilities have been informative models for uncovering natural mechanisms by which tissue damage activates stem or progenitor cells for injury repair. The timing, location, and extent of injuries are not predetermined, requiring the existence of mechanisms that instruct tissue restoration activities that perfectly counter the effects of damage. A key question to understand this process is how regenerative tissue redefines territories removed by injury, and it is hypothesized this is related to as-yet undiscovered systems that robustly regulate tissue proportionality across large length scales. To begin to address this question, it is essential to define the cell signaling systems that underlie regional identity and proportional growth. While regenerative tissues have been extensively probed for the roles of injury-induced signals and the involvement of stem or progenitor cells, much less is known about the molecular and developmental processes that enable the restoration of form after injury and its maintenance through adult growth. In the aims of this grant, this deficit is addressed by leveraging expertise in the planarian system, which uniquely allows for the study of signaling that regulates re-scaling of tissues through regeneration, to elucidate the regulatory and developmental mechanism that generates and restores tissue proportionality after injury. Uncovering fundamental mechanisms used by organisms to control tissue proportionality will provide foundational insights into understanding diseases of growth misregulation, the nature of proportional growth, and the control of stem cells for tissue regeneration.

项目概要/摘要 具有再生能力的生物体已成为揭示自然机制的信息模型 哪些组织损伤会激活干细胞或祖细胞进行损伤修复。时间、地点和范围 损伤不是预先确定的，需要存在指导组织恢复活动的机制 完美抵消损坏的影响。理解这个过程的一个关键问题是如何再生 组织重新定义了因损伤而移除的区域，并且推测这与尚未发现的有关 能够在大长度尺度上强有力地调节组织比例的系统。开始解决这个问题 问题，有必要定义作为区域特征和比例基础的细胞信号系统 生长。虽然再生组织已被广泛研究损伤诱导信号的作用和 干细胞或祖细胞的参与，但对分子和发育过程知之甚少 能够在受伤后恢复形态并在成年生长过程中维持形态。为了达到这个目的 授予，这一缺陷可以通过利用涡虫系统的专业知识来解决，该系统独特地允许 研究通过再生调节组织重新缩放的信号传导，以阐明调节和 损伤后产生和恢复组织比例的发育机制。揭秘 生物体用于控制组织比例的基本机制将提供基础见解 了解生长失调疾病、比例生长的本质以及茎的控制 用于组织再生的细胞。