Stem Cell Lineage Selectionin Protochordate

所有多细胞生物都起源于一小部分全能胚胎干细胞，这些干细胞可以扩张并 分化成成熟个体的组织和器官。然而，个人并不是静态的实体，而且 在正常生长和衰老过程中，或在受伤后，分化的细胞、组织和器官必须得到补充。 然后重生。在成人中，这种再生过程被认为是由茎或祖细胞执行的。 在个体的整个生命周期中保持扩张和分化能力的细胞。然而， 这些细胞的性质以及控制它们的扩张和 辨证分型认识不深，但具有重要的临床意义。使用模型系统 提供实验上可获得和可靠的再生潜力可以帮助我们理解 再生的生物学基础。这项提案的总体目标旨在隔离和 鉴定原始脊索虫Botryllus schlosseri的干细胞。B.schlosseri提供了一种独特的 研究干细胞生物学的模型有两个原因。首先，再生是人类生命史的重要组成部分 Botryllus：在高度协调的发育过程中，Botryllus成虫自我再生，包括 所有的体细胞组织和生殖系，每周。其次，在自然条件下，负责 这种再生可以在两个个体之间动员和移植。一旦被移植，这些细胞就可以 繁殖和竞争宿主干细胞，并在水平上独立接管另一个个体 在称为生殖系细胞的过程中，在宿主的剩余生命周期中的生殖系和胞体中 寄生(GCP)或体细胞寄生(SCP)，我们已经证明了有一个遗传 这是这一进程的基础。干细胞生物学的基本、保守和重要方面，如自我 干细胞的更新能力、归巢或扩增和分化动力学必须是 一种基因可以与另一种基因的干细胞竞争。这项提案的总体目标是使用 本系统前瞻性分离负责GCP和SCP的细胞(S)，测定细胞和 这些细胞的分子生物学表型(S)，并将这些表型与寄生能力相关联。

All multicellular organisms originate from a small set of totipotent embryonic stem cells which expand and differentiate into tissues and organs of a mature individual. However, individuals are not static entities, and during normal growth and aging, or after injury, differentiated cells, tissues and organs must be replenished and regenerated. In adults, this process of regeneration is thought to be carried out by stem or progenitor cells which retain the capacity to expand and differentiate throughout the lifespan of the individual. However, the nature of these cells and the cellular and molecular mechanisms which control their expansion and differentiation are not well-understood, but have important clinical significance. Using model systemsthat provide experimentally accessible and reliable regenerative potential can facilitate our understanding of the biology underlying regeneration. The overall objectives of this proposal are designed to isolate and characterize stem cells from the primitive chordate, Botryllus schlosseri. B. schlosseri provides a unique model to study stem cell biology for two reasons. First, regeneration is a major part of the life history of Botryllus: in a highly coordinated developmental process, Botryllus adults regenerate themselves, including all somatic tissues and the germline, every week. Secondly, under natural conditions the cells responsible for this regeneration can mobilize and transplant between two individuals. Once transplanted, these cells can proliferate and out compete host stem cells and take over the other individual independently at the level of the germline and in the soma for the remaining lifetime of the host, in processes called germline cell parasitism (gcp) or somatic cell parasitism (scp), respectively, and we have shown that there is a genetic basis to this process. Fundamental, conserved and important aspects of stem cell biology, such as self- renewal capacity, homing or expansion and differentiation kinetics must underlie the ability of a stem cell of one genotype to out compete a stem cell of another genotype. The overall goals of this proposal are to use this system to prospectively isolate the cell(s) responsible for gcp and scp, determine the cellular and molecular biological phenotype of these cell(s), and correlate those phenotypes with parasitic capability.