Epidermal Stem Cells Can Reverse Their Fate in Developm*

描述(申请人提供)：持续更新的成人的动态平衡 组织，如表皮和造血系统，是由 体细胞干细胞。这些是未分化的S精灵更新细胞，它 也产生子代瞬时放大(TA)细胞。TA细胞经历一种 在分化和离开细胞之前的有限数量的细胞分裂 增殖室，而干细胞持续存在于整个 生物体的寿命[1]。我们首先直接展示了异质性 1981年，我们发现了一种小的表皮增殖细胞 Cells[2]。最近，我们开发了一种排序方法，它可以产生一个可行的 小鼠表皮中的体细胞群体[3]。我们展示了这些 干细胞具有再生表皮和永久修复的能力。 在再生组织中表达重组基因。几年前是这样的 证明了体细胞干细胞具有显著的能力 分化为其他组织类型[4]，并具有预期的可塑性 胚胎干细胞。我们的初步数据表明，这也可能是 对于表皮干细胞来说是正确的，它们具有分化的能力 外胚层和间质来源的组织，这表明 体细胞表皮干细胞可以穿越外胚层-中胚层发育 障碍。因此，我们的假设是：1)体表干细胞可以 在发育过程中以类似于胚胎干细胞的方式发挥作用，以及2) 环境(外在)因素影响儿童的发育途径 体细胞干细胞。为了检验这些假设，我们建议1)确定 胚泡内注射表皮干细胞是否会改变其表型 在发育期间，以及2)确定注射的表皮干细胞 细胞永久地作为它们所在的组织或器官的一部分发挥作用。

DESCRIPTION (provided by applicant): Homeostasis of continuously renewing adult tissues, such as the epidermis and the hematopoietic system, is maintained by somatic stem cells. These are undifferentiated, s elf-renewing cells, which also produce daughter transient amplifying (TA) cells. TA cells undergo a finite number of cell divisions before differentiating and leaving the proliferative compartment, whereas the stem cells persist throughout the lifetime of the organism [1]. We first directly demonstrated heterogeneity in the proliferative cells of the epidermis in 1981 when we identified a small cells [2]. Recently, we developed a sorting method that yields a viable population of somatic stem cells from mouse epidermis [3]. We showed that these stem cells have the capacity to regenerate the epidermis and to permanently express a recombinant gene in the regenerated tissue. A few years ago it was demonstrated that somatic stem cells have the remarkable capacity to differentiate into other tissue types [4], and have a plasticity only expected of embryonic stem cells. Our preliminary data suggest that this may also be true for epidermal stem cells, and that they have the ability to differentiate into both ectodermally- and mesenchymally-derived tissues, suggesting that somatic epidermal stem cells can cross the ectoderm-mesoderm developmental barrier. Therefore, our hypotheses are 1) that somatic epidermal stem cells can function in a similar manner to embryonic stem cells during development, and 2) that environmental (extrinsic) factors influence the developmental pathway for somatic stem cells. To test these hypotheses, we propose 1) To determine whether epidermal stem cells injected into blastocysts alter their phenotype during development, and 2) to determine whether the injected epidermal stem cells permanently function as part of the tissue or organ in which they reside.