Epidermal Stem Cells Can Reverse Their Fate in Developm*

描述（由申请人提供）：不断更新的成人体内平衡 表皮和造血系统等组织是由 成体干细胞。这些是未分化的、自我更新的细胞， 还产生子代瞬时放大 (TA) 细胞。 TA 细胞经历 在分化和离开细胞之前进行有限次数的细胞分裂 增殖室，而干细胞在整个增殖室中持续存在 生物体的寿命[1]。我们首先直接证明了异质性 1981 年，我们发现了表皮的增殖细胞 细胞[2]。最近，我们开发了一种排序方法，可以产生可行的结果 来自小鼠表皮的成体干细胞群[3]。我们证明了这些 干细胞具有再生表皮并永久修复的能力 在再生组织中表达重组基因。几年前它是 研究表明，成体干细胞具有非凡的能力 分化成其他组织类型[4]，并且具有预期的可塑性 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，并且它们具有分化的能力 进入外胚层和间充质来源的组织，表明 体细胞表皮干细胞可跨越外胚层-中胚层发育 障碍。因此，我们的假设是1）体细胞表皮干细胞可以 在发育过程中以与胚胎干细胞类似的方式发挥作用，并且2) 环境（外在）因素影响发育途径 成体干细胞。为了检验这些假设，我们建议 1) 确定 注入囊胚的表皮干细胞是否会改变其表型 在发育过程中，2) 确定注射的表皮干是否 细胞作为其所在组织或器官的一部分永久发挥作用。

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.