Urothelial Stem Cells

尿路上皮干细胞

• 批准号: 9383628
• 负责人: Tung-Tien Sun
• 金额: $ 68.92万
• 依托单位: NEW YORK UNIVERSITY SCHOOL OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-09-01 至 2021-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9383628
• 关键词: Adult; Attention; Biological Process; Bladder; Bladder Diseases; Bladder Urothelium; Cell Lineage; Cell Separation; Cells; Cornea; Diagnosis; Disease; Engineered Gene; Epidermis; Epithelium; Goals; Growth; Harvest; Homeostasis; In Vitro; Infection; Injury; Interstitial Cystitis; Label; Lead; Ligands; Location; Mesenchyme; Metaplasia; Molecular; Natural regeneration; Organ; Pathway interactions; Pattern; Play; Principal Investigator; Property; Regulation; Renal pelvis; Rest; Role; Site; Stem cells; Stratum Basale; Tissue Engineering; Tissues; Ureter; Urethra; Urinary tract; Urinary tract infection; Urothelial Cell; Urothelium; Work; Wound Healing; base; beta catenin; corneal epithelium; experience; gene therapy; improved; in vivo; keratinocyte; limbal; migration; molecular marker; novel; progenitor; repaired; tissue repair; tumorigenesis; ureteric orifice

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.

概括 该项目基于主要研究者在研究尿路上皮方面的丰富经验 分化和角质形成细胞细胞，旨在更好地了解膀胱 尿路上皮干细胞。尽管尿路上皮干细胞在体内平衡中的重要性，但 膀胱的再生和肿瘤发生，它们的精确位置和特性仍然是 不完全理解。有几个问题阻碍了该领域的进展。例如， 由于“尿液尿液”一词用于描述覆盖尿道粉的表达上皮 整个尿道，包括肾脏骨盆，输尿管，膀胱和近端尿道，通常假定 所有这些地点的尿尿都相同。此外，关于膀胱尿路干细胞的研究具有 我们仅限于膀胱本身，没有注意 膀胱合适。但是，我们最近发现输尿管孔连接（UVJ） 拥有一大批被强标记的（保留标签）干细胞。主要集群的存在 位于膀胱孔附近的膀胱外部的干细胞被提醒 角膜上皮的干细胞驻留在缘地区的角膜外，而 卵泡隆起的干细胞虽然在表皮之外，但仍参与表皮修复。 该项目的目标是更好地了解UVJ STEM的属性和体内功能 细胞及其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体内骨稳态，再生和疾病的理解 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，（ii） 尿路上皮干细胞，（iii）Wnt途径在调节尿路上皮茎中的可能作用 细胞。