Expression Programs of Intestinal Cell Differentiation

肠细胞分化的表达程序

• 批准号: 6966493
• 负责人: Xin Chen
• 金额: $ 15.15万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-09-15 至 2007-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6966493
• 关键词: biotechnology; cell differentiation; clinical research; cytogenetics; gastrointestinal epithelium; gene expression profiling; genetic markers; histogenesis; human tissue; immunocytochemistry; in situ hybridization; intestinal villi; laser capture microdissection; microarray technology; nucleic acid amplification techniques; polymerase chain reaction; stem cells

DESCRIPTION (provided by applicant): Intestinal epithelial cells undergo rapid and continuous cell renewal through out life. This self-renewal is maintained by a group of multipotent stem cells located at intestinal crypts. These stem cells give rise to progenitor cells, which then differentiate into different cell lineages and migrate up along the intestinal villi. Molecular genetics of this differentiation process is still poorly defined. Intestinal stem cells provide promising treatment strategy for some GI diseases, for example, inflammatory bowel disease and gut failure. However, little is known of specific markers for these stem cells, which make the isolation and culture of the stem cells difficult in vitro. We hypothesize that there are distinct gene expression programs that are associated with the developmental program of the intestine, i.e., different regions of the intestinal villi have different expression profiles. We further hypothesize that the stem cells located in the crypt side of the intestine share similar "sternness" genes with human embryonic stem cells. In this application, we propose the following aims: Aim 1: To obtain a gene expression profile of different regions of intestinal villi; Aim 2: To identify genes that are associated with different regions of intestinal epithelium, as well as genes that may be related to the intestinal stem cells; and Aim 3: To validate the expression and study the cellular localization of candidate genes. In summary, the proposed exploratory study of gene expression patterns associated with intestinal epithelial cells will provide a comprehensive picture of the differentiation program of these cells. Moreover, the genes that may be associated with intestinal stem cells will provide markers for identification, purification and characterization of these cells.

描述（由申请人提供）：肠上皮细胞在一生中经历快速和连续的细胞更新。这种自我更新是由位于肠隐窝的一组多能干细胞维持的。这些干细胞产生祖细胞，然后分化成不同的细胞系，并沿着肠绒毛向上迁移。这种分化过程的分子遗传学仍不清楚。肠道干细胞为炎症性肠病和肠道衰竭等胃肠道疾病的治疗提供了有希望的治疗策略。然而，对这些干细胞的特异性标记知之甚少，这使得干细胞的体外分离和培养变得困难。我们假设存在与肠道发育程序相关的不同基因表达程序，即肠绒毛的不同区域具有不同的表达谱。我们进一步假设，位于肠隐窝侧的干细胞与人类胚胎干细胞具有相似的“严厉性”基因。在这项应用中，我们提出以下目的：目的1：获得肠绒毛不同区域的基因表达谱；目的2：鉴定与肠上皮不同区域相关的基因，以及可能与肠干细胞相关的基因；目的3：验证候选基因的表达并研究候选基因的细胞定位。总之，对肠上皮细胞相关基因表达模式的探索性研究将为这些细胞的分化过程提供一个全面的图景。此外，可能与肠道干细胞相关的基因将为这些细胞的鉴定、纯化和表征提供标记。