Regulation of whole-body regeneration

全身再生的调节

• 批准号: 10623992
• 负责人: Christian Petersen
• 金额: $ 54.1万
• 依托单位: NORTHWESTERN UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-04-01 至 2028-03-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10623992
• 关键词: Adult; Biological Models; Cell Count; Cell Differentiation process; Developmental Process; Distant; Event; Expression Profiling; Grant; Growth; Homeostasis; Information Systems; Injury; Maintenance; Modeling; Molecular; Natural regeneration; Organism; Outcome; Pathway interactions; Planarians; Platyhelminths; Process; RNA interference screen; Regulation; Research; Role; Signal Induction; Signal Transduction; Source; System; Tissues; Work; adult stem cell; injury and repair; programs; regenerative; regenerative growth; regenerative tissue; response; restoration; stem cells; tissue repair; transcriptomics; wound

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. Such systems require not only sources for newly forming differentiated cells and initial responses to wounding, but also critically, spatial information systems that signal tissue presence/absence in order to control appropriate regeneration outcomes and restore tissue to its original scale and cell number. 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. This grant seeks to understand the factors involved in the early symmetry- breaking events after injury, the process of establishing and using signaling centers for control of regenerative growth, the mechanism by which whole-body regeneration can robustly restore tissue proportionality and restore homeostasis, and identify the control mechanisms used by progenitor cells in whole body regeneration. The work will compare regeneration mechanisms in two distantly evolved model systems, the planarian Schmidtea mediterranea and the acoel Hofstenia miamia, each capable of whole-body regeneration using Piwi-expressing pluripotent adult stem cells termed neoblasts. Using expression profiling, RNAi screening and spatial transcriptomics, these studies will reveal what factors and strategies of whole-body regeneration are ancient and conserved. These approaches will reveal foundational mechanisms used by organisms to control adult tissue repair, growth, and homeostasis.

项目概要/摘要 具有再生能力的生物体已成为揭示自然现象的信息丰富的模型 组织损伤激活干细胞或祖细胞进行损伤修复的机制。这样的 系统不仅需要新形成的分化细胞的来源和对细胞的初始反应 伤害，但也至关重要的是，空间信息系统发出组织存在/不存在的信号 为了控制适当的再生结果并将组织恢复到其原始规模和细胞 数字。虽然再生组织已被广泛研究损伤诱导的作用 信号以及干细胞或祖细胞的参与，人们对分子的了解知之甚少。 以及能够在受伤后恢复形态并维持其状态的发育过程 通过成人的成长。这笔赠款旨在了解早期对称性所涉及的因素 - 受伤后突发事件，建立和使用信号中心来控制的过程 再生生长，全身再生可以稳健恢复的机制 组织比例并恢复稳态，并确定所使用的控制机制 全身再生中的祖细胞。这项工作将比较再生机制 两个遥远进化的模型系统，涡虫 Schmidtea mediterranea 和 acoel Hofstenia miamia，每个都能够利用表达 Piwi 的多能性进行全身再生 成体干细胞称为新生细胞。使用表达谱、RNAi 筛选和空间分析 转录组学，这些研究将揭示全身再生的因素和策略 古老且保存完好。这些方法将揭示所使用的基本机制 控制成人组织修复、生长和体内平衡的生物体。