Experimental Hematopoietic Stem Cell Growth

描述(申请人提供)：造血干细胞已被 这是多年来密集调查的主题。直到最近， 研究主要考察了含有极少数实际HSC的细胞群体。 这些细胞的稀有使得很难获得足够数量的 用于研究的细胞。使这个问题复杂化的是潜在的泛函 HSC群体的表型多样性。我们已经开发出一种HSC跟踪 允许我们在骨髓移植后恢复HSC的检测方法 小鼠宿主，这将使我们第一次能够研究 潜在同质群体的分子和细胞特征 从成人骨髓中提取的HSC。功能方面包括干细胞 体外和体内的增殖、分化、存活和归巢。这个 表型特征包括新奇的(以及从 人口研究)细胞表面标记以及分子调控 例如p27，一种细胞周期蛋白激酶抑制物，可能与 HSC静止。此外，辅助细胞群可能很好地发挥了 在HSC功能中的调节作用。我们的计划是能够区分 在HSC细胞分裂之间导致HSC的维持 舱室、舱室的扩张或舱室的耗尽。 最后，我们将继续研究发育不成熟的HSC 植入潜能基因的表达和可塑性。

DESCRIPTION (provided by applicant): Hematopoietic stem cells (HSC) have been the subject of intense investigation for many years. Until recently, the studies primarily examined populations of cells containing very few actual HSC. The rarity of these cells has made it difficult to obtain sufficient numbers of cells for study. Compounding this problem is the potential functional phenotypic diversity of the HSC populations. We have developed an HSC tracking assay which has allowed us to recover HSC following bone marrow transplantation into murine hosts which will allow us for the first time to study both the molecular and cellular characteristics of a potentially homogeneous population of HSC from adult bone marrow. The functional aspects include stem cell proliferation, differentiation, survival and homing in-vitro and in-vivo. The phenotypic characterization includes novel (as well as those suggested from population studies) cell surface markers as well as molecular regulatory molecules such as p27, a cyclin kinase inhibitor which could be responsible for HSC quiescence. In addition, accessory cell populations may very well play a regulatory role in HSC functions. It is our plan to be able to distinguish between HSC cellular divisions which result in maintenance of the HSC compartment, expansion of the compartment or depletion of the compartment. Finally, we will continue to examine developmentally immature HSC for engraftment potential gene expression and plasticity.