Stem Cell Lineage Selectionin Protochordate

所有的多细胞生物都起源于一小部分全能的胚胎干细胞，这些细胞可以扩增并 分化成成熟个体的组织和器官。然而，个人不是静态的实体， 在正常生长和衰老期间，或在损伤之后，必须补充分化的细胞、组织和器官， 然后重生在成年人中，这一再生过程被认为是由茎或祖细胞进行的。 在个体的整个生命周期中保持扩增和分化能力的细胞。然而，在这方面， 这些细胞的性质以及控制其扩张的细胞和分子机制， 分化尚未得到充分理解，但具有重要的临床意义。使用模型系统， 提供实验上可获得的和可靠的再生潜力可以促进我们对 再生的生物学基础本提案的总体目标是隔离和 从原始脊索动物，Botryllus schlosseri中提取干细胞。B。施洛塞里提供了一个独特的 研究干细胞生物学有两个原因。首先，再生是生命史的一个重要组成部分， 在一个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细胞第二，在自然条件下， 这种再生可以在两个个体之间移动和移植。一旦移植，这些细胞可以 增殖和竞争宿主干细胞，并在细胞水平上独立地接管另一个个体。 在宿主的剩余寿命中，在生殖细胞和索马中， 寄生（gcp）或体细胞寄生（scp），我们已经表明，有一个遗传 这个过程的基础。干细胞生物学的基本、保守和重要方面，如自 更新能力，归巢或扩增和分化动力学必须是干细胞的能力的基础， 一种基因型胜过另一种基因型的干细胞。本提案的总体目标是利用 该系统用于前瞻性地分离负责GCP和SCP的细胞，确定细胞和 这些细胞的分子生物学表型，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.