Urothelial Stem Cells

总结 该项目建立在主要研究者在研究尿路上皮细胞方面的丰富经验的基础上。 分化和角质形成细胞干细胞，旨在提供更好的了解膀胱 尿路上皮干细胞尽管尿路上皮干细胞在体内平衡中至关重要， 膀胱的再生和肿瘤发生，它们的精确位置和性质仍然是未知的。 不完全理解。有几个问题阻碍了这一领域的进展。比如说， 由于术语“尿路上皮”用于描述覆盖膀胱的表达尿斑蛋白的上皮， 包括肾盂、输尿管、膀胱和近端尿道在内的整个泌尿道， 所有这些部位的尿路上皮都是一样的此外，对膀胱尿路上皮干细胞的研究 仅限于膀胱本身，没有注意到膀胱外的尿路上皮干细胞。 膀胱本身然而，我们最近发现，输尿管膀胱连接部（UVJ） 含有大量强标记（标记保留）干细胞。主要集群的存在 膀胱外的干细胞，位于膀胱输尿管口附近，让人想起 角膜上皮，其干细胞位于角膜缘区中的角膜本身之外，以及 毛囊隆突干细胞，虽然在表皮外，但参与表皮修复。 本项目的目标是更好地了解UVJ股骨柄的特性和体内功能 细胞，以及它们与膀胱和输尿管尿路上皮干细胞的关系。这些研究可以 提高我们对尿路上皮稳态，再生和疾病的理解，包括 化生和尿路感染。为了实现这些目标，我们将追求三个具体目标， 将研究：（i）尿路上皮谱系和干细胞的分子标记物，（ii） 尿路上皮干细胞，和（iii）Wnt途径在调节尿路上皮干细胞中的可能作用 细胞

Summary This project builds upon the Principal Investigator’s extensive experience in studying urothelial differentiation and keratinocyte stem cells, and aims at providing a better understanding of bladder urothelial stem cells. Despite the central importance of urothelial stem cells in the homeostasis, regeneration and tumorigenesis of the bladder, their precise location and properties are still incompletely understood. There are several issues that hinder the progress in this field. For example, since the term “urothelium” is used to describe the uroplakin-expressing epithelium that covers the entire urinary tract including the renal pelvis, ureter, bladder and proximal urethra, it is often assumed that urothelia of all these sites are the same. In addition, studies on bladder urothelial stem cells have been limited to the bladder per se and no attention has been paid to urothelial stem cells outside of the bladder proper. However, we have recently discovered that ureterovesicular junction (UVJ) harbors a large cluster of strongly labeled (label-retaining) stem cells. The presence of a major cluster of stem cells outside of the bladder proper, located near the bladder-ureter orifice, is reminiscent of the corneal epithelium whose stem cells reside outside of the corneal proper in the limbal zone, and the follicular bulge stem cells that, although outside of the epidermis, are involved in epidermal repair. The goals of this project are to better understand the properties and in vivo functions of the UVJ stem cells, and their relationships with the bladder and ureteral urothelial stem cells. These studies can improve our understanding of urothelial homeostasis, regeneration, and diseases including metaplasia and urinary tract infection. To reach these goals, we will pursue three Specific Aims that will study: (i) molecular markers of urothelial lineages and stem cells, (ii) biological functions of the urothelial stem cells, and (iii) the possible roles of the Wnt pathway in regulating the urothelial stem cells.