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.

项目总结/摘要 具有再生能力的生物体一直是揭示自然生态系统的信息模型。 组织损伤激活干细胞或祖细胞进行损伤修复的机制。等 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， 创伤，但也至关重要的是，空间信息系统，信号组织存在/不存在， 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， number.虽然再生组织已被广泛探索损伤诱导的作用， 信号和干细胞或祖细胞的参与，更少的是知道的分子 和发育过程，使受伤后的形式恢复和维护 通过成人成长。这项资助旨在了解早期对称性所涉及的因素- 受伤后的突发事件，建立和使用信号中心控制的过程， 再生性生长，全身再生的机制可以强劲地恢复 组织比例和恢复稳态，并确定控制机制所使用的 祖细胞在全身再生。这项工作将比较再生机制， 两个远距离进化的模式系统，涡虫Schmidtea mediterranea和acoel Hofstenia miamia，每一个都能够使用表达Piwi的多能干细胞进行全身再生。 成体干细胞称为neoblast。使用表达谱分析、RNAi筛选和空间分析， 转录组学，这些研究将揭示什么因素和策略的全身再生 是古老而保守的。这些方法将揭示 生物体控制成人组织修复，生长和体内平衡。