Cell Lineage Analysis in Vertebrate Limb Regeneration

描述（由申请人提供）：再生过程了解甚少。这项提议旨在扩大对脊椎动物四肢再生如何发生的科学理解。在尾纲两栖动物中，残肢的再生被认为是通过残肢组织去分化产生胚基，然后是细胞增殖和模式事件，指导细胞再分化产生新肢的组成部分。在本提案的目标1中，将追踪再生蝾螈肢体内的单个细胞系，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Aim 2中进行探讨。在哺乳动物中，肢体再生仅限于指尖，随着年龄的增长，远端也越来越受限制。目标2将验证一种假设，即在手指尖端发现的一组特定的干细胞，即表达msxml的细胞，具有再生能力。为了验证这一假设，需要将msxl细胞移植到更近的位置，并确定它们是否能在那里诱导再生。如果是这样，是否可以对细胞进行操作以使近端元素再生？

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?