Cell Lineage Analysis in Vertebrate Limb Regeneration

脊椎动物肢体再生中的细胞谱系分析

• 批准号: 7157993
• 负责人: JESSICA L. WHITED
• 金额: $ 4.4万
• 依托单位: HARVARD MEDICAL SCHOOL
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-09-01 至 2009-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7157993
• 关键词: Retroviridae; Urodela; aging; amputation; blastema; cell differentiation; cell growth regulation; cell population study; cell transplantation; developmental genetics; embryogenesis; gene expression; homeobox genes; laboratory mouse; limb regeneration; postdoctoral investigator; species difference; stem cell transplantation; stem cells; transfection /expression vector

DESCRIPTION (provided by applicant): Regenerative processes are poorly understood. This proposal aims to expand scientific understanding of how regeneration occurs in vertebrate limbs. In urodele amphibians, regeneration of a lost limb is thought to occur by dedifferentiation of remaining tissues to create a blastema, followed by cell proliferation and patterning events that direct the redifferentiation of cells to create components of the new limb. In Aim 1 of this proposal, individual cell lineages within a regenerating axolotl limb will be traced to determine the source of cells used for dedifferentiation and the fate of these cells within the new limb. The potential contribution of stem cells to limb regeneration in mammals will be explored in Aim 2. In mammals, limb regeneration is restricted to digit tips and becomes increasingly restricted distally with age. Aim 2 will test the hypothesis that a specific set of stem cells, msxl-expressing cells, found at the digit tips confers regenerative ability. Testing this hypothesis will involve transplanting msxl cells to more proximal locations and determining if they can induce regeneration there. If so, can the cells be manipulated to allow regeneration of proximal elements?

描述（由申请人提供）：人们对再生过程知之甚少。该提案旨在扩大对脊椎动物肢体再生如何发生的科学理解。在有尾目两栖动物中，失去的肢体的再生被认为是通过剩余组织的去分化产生胚基，然后进行细胞增殖和模式化事件来指导细胞的再分化以产生新肢体的组成部分。在该提案的目标 1 中，将追踪再生蝾螈肢体内的单个细胞谱系，以确定用于去分化的细胞来源以及这些细胞在新肢体内的命运。干细胞对哺乳动物肢体再生的潜在贡献将在目标 2 中探讨。在哺乳动物中，肢体再生仅限于指尖，并且随着年龄的增长，远端的再生受到越来越多的限制。目标 2 将检验以下假设：指尖发现的一组特定干细胞（表达 msxl 的细胞）具有再生能力。测试这一假设将涉及将 msxl 细胞移植到更近的位置，并确定它们是否可以诱导那里的再生。如果是这样，是否可以操纵细胞以允许近端元件再生？