Epidermal Stem Cells Can Reverse Their Fate in Developm*

表皮干细胞可以逆转其发育命运*

• 批准号: 6533043
• 负责人: JACKIE R BICKENBACH
• 金额: $ 7.35万
• 依托单位: UNIVERSITY OF IOWA
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-09-28 至 2003-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6533043
• 关键词: cell differentiation; cell population study; cell proliferation; cell sorting; developmental genetics; embryogenesis; embryonic stem cell; gene expression; genetically modified animals; histogenesis; homeostasis; immunocytochemistry; laboratory mouse; microinjections; newborn animals; phenotype; skin; transfection

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.

描述（由申请人提供）：持续更新成人的稳态 组织，如表皮和造血系统，是由 体细胞这些是未分化的自我更新细胞， 也产生子瞬时扩增（TA）细胞。TA细胞经历一个 在分化和离开细胞之前，细胞分裂次数有限 增殖区室，而干细胞持续整个 生物体的寿命[1]。我们首先直接证明了 1981年，当我们发现一个小的表皮细胞时， 细胞[2]。最近，我们开发了一种排序方法， 来自小鼠表皮的体干细胞群体[3]。我们发现这些 干细胞有能力再生表皮， 在再生组织中表达重组基因。几年前是 证明了体干细胞具有非凡的能力， 分化成其他组织类型[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 表皮干细胞也是如此， 外胚层和间充质来源的组织，这表明， 体细胞表皮干细胞可跨越外胚层-中胚层发育 屏障因此，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）因素影响发展途径， 体细胞为了验证这些假设，我们建议：1）确定 表皮干细胞注射到胚泡中是否会改变其表型 在发育过程中，和2）以确定是否注射表皮干 细胞永久地作为它们所驻留的组织或器官的一部分发挥功能。