Stem Cell Plasticity after Blastocyst Implantation

描述（由申请人提供）： 最近的几项研究表明，组织来源的干细胞不仅可以 分化成获得它们的组织的细胞，而且 来自其他组织的。 我们一直对 CNS来源的干细胞的分化能力（我们称之为可塑性） 并假设一种检测方法是将这些细胞植入 并在随后评估对所得小鼠的掺入。 发展 我们的研究结果表明，这些细胞的稳健掺入， 神经组织，包括骨髓，在那里它们表达谱系标记 分化的造血细胞，骨骼肌肉和胃肠道。 我们相信这个模型提供了一个独特的洞察干细胞可塑性 由于植入和生产的效率很高， 正常的幼崽 我们建议通过以下方式跟进我们的研究 具体目标：1）我们将确定是否将干细胞纳入 胚泡作为干细胞亚群或类型的函数而变化，我们将 建立一个神经干细胞的病毒库， 亚群存在，以及比较神经干细胞与骨髓 基质细胞的能力纳入囊胚; 2）我们将 确定是否将神经干细胞掺入其他组织 通过骨髓细胞移植使它们发挥功能 从嵌合体幼崽中获得致死辐射小鼠，并评估 神经干细胞是否可以修复胚胎致命的遗传缺陷， 3）我们将评估神经干细胞是否保留其功能 胚泡后发育成嗅觉中间神经元的能力 移植，并确定是否在胚泡植入 阶段可以修复缺乏髓鞘的小鼠。

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.