Stem Cell Plasticity after Blastocyst Implantation

描述(由申请人提供)： 最近的一些研究表明，组织来源的干细胞不仅可以 分化为获得它们的组织的细胞，但也 那些来自其他组织的。我们一直对以下范围感兴趣 中枢神经干细胞的分化能力(我们称之为可塑性) 并假设一种测试方法是将这些细胞植入 转化为胚泡细胞，并在稍后评估并入所产生的小鼠 发展。我们的结果表明，这些细胞可以很好地整合到 神经外组织，包括骨髓，在那里它们表达谱系标志 分化的造血细胞、骨肌和胃肠道。 我们相信这个模型为干细胞的可塑性提供了一个独特的视角。 因为表面上的植入和生产效率很高 正常的小狗。我们建议通过处理以下问题来跟进我们的研究 具体目标：1)我们将确定将干细胞掺入 胚泡随着干细胞亚群或类型的不同而不同，我们将 创建神经干细胞的逆转录病毒文库，以评估特定的 亚群的存在以及神经干细胞与骨髓的比较 基质细胞结合到囊胚中的能力；2)我们将 确定是否将神经干细胞掺入其他组织 通过进行细胞的骨髓移植使其具有功能 从嵌合体幼鼠获得的致死照射小鼠和评估 神经干细胞能否修复胚胎致死的遗传缺陷 骨；以及3)我们将评估神经干细胞是否保持其功能 胚泡发育为嗅觉间神经元的能力 移植，并确定它们在囊胚处的植入 STAGE可以修复髓鞘缺失的小鼠。

DESCRIPTION (provided by applicant): Several recent studies indicate that tissue-derived stem cells can not only differentiate into cells of the tissue from which they are obtained, but also those from other tissues. We have been interested in the range of differentiative capacity (which we term plasticity) of CNS derived stem cells and hypothesized that one way to assay this would be to implant these cells into blastocyts and assess incorporation into the resulting mice later in development. Our results indicate a robust incorporation of these cells into extraneural tissues including bone marrow, where they express lineage markers of differentiated hematopoietic cells, bone muscle and GI tract. We believe this model provides a unique insight into stem cell plasticity because of the high efficiency of implantation and production of apparently normal pups. We propose to follow-up our studies by addressing the following specific aims: 1) We will determine whether incorporation of stem cells into blastocysts varies as a function of stem cell subpopulation or type, we will create a retorviral library of neural stem cells to assess whether specific subpopulations exist as well as comparing neural stem cells with marrow stromal cells in their ability to incorporate into blastocysts; 2) We will determine whether incorporation of neural stem cells into other tissues renders them functional by performing bone marrow transplantation of cells obtained from chimeric pups into lethally irradiated mice and assessing whether neural stem cells can repair a embryonically lethal genetic defect in bone; and 3) We will assess whether neural stem cells retain their functional capacity to develop into olfactory interneurons after blastocyst transplantation and determine whether their implantation at the blastocyst stage can repair mice with an absence of myelin.