Regulation of Active and Quiescent Intestinal Stem Cells

活性和静态肠干细胞的调节

• 批准号: 9412209
• 负责人: Kelley Yan
• 金额: $ 14.34万
• 依托单位: COLUMBIA UNIVERSITY HEALTH SCIENCES
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-09-01 至 2018-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9412209
• 关键词: Regulation; Active; Quiescent; Intestinal; Stem

DESCRIPTION (provided by applicant): There is emerging evidence that distinct populations of actively cycling and quiescent intestinal stem cells (ISCs) co-exist within the small intestine epithelium and function cooperatively in tissue renewal. This proposal explores the hypothesis that these ISC populations are regulated by distinct sets of extracellular signals involved in organ size control and oxygen-sensing. This hypothesis is evaluated by three Specific Aims: (1) to explore the Hippo signaling pathway, implicated in controlling organ size, in regulating the regenerative responses of active and quiescent ISC populations, (2) to examine metabolic regulation of active and quiescent ISCs by the oxygen-sensing pathway, and (3) to determine the molecular signatures of active versus quiescent ISCs by comparative gene expression profiling. These Specific Aims will be achieved by employing rigorous mouse genetics to examine ISCs in vivo within their stem cell niches and validated ex vivo clonogenic culture techniques that allow for sustained proliferation and multi-lineage differentiation of single isolated ISCs. Achievement of these Aims should provide insight into the molecular differences between active and quiescent ISCs at the transcriptional level and their differential regulation by diverse pathways governing organ size and metabolism.

描述（由申请人提供）：新出现的证据表明，活跃循环和静止肠干细胞（ISC）的不同群体共存于小肠上皮内，并在组织更新中协同发挥作用。该提案探讨了这样的假设：这些 ISC 群体受到参与器官大小控制和氧感应的不同细胞外信号的调节。该假设通过三个具体目标进行评估：(1) 探索 Hippo 信号通路，涉及控制器官大小、调节活跃和静止 ISC 群体的再生反应，(2) 通过氧传感通路检查活跃和静止 ISC 的代谢调节，以及 (3) 通过比较基因表达来确定活跃与静止 ISC 的分子特征 分析。这些具体目标将通过采用严格的小鼠遗传学来检查体内 ISC 的干细胞生态位，并验证离体克隆培养技术，以实现单个分离的 ISC 的持续增殖和多谱系分化。这些目标的实现应该能够深入了解活性 ISC 和静态 ISC 在转录水平上的分子差异以及它们的差异调节 控制器官大小和新陈代谢的多种途径。

项目成果

Ascl2 reinforces intestinal stem cell identity.

Ascl2 增强肠道干细胞的身份。

• DOI: 10.1016/j.stem.2015.01.014
• 发表时间: 2015
• 期刊: Cell stem cell
• 影响因子: 23.9
• 作者: Yan,KelleyS;Kuo,CalvinJ
• 通讯作者: Kuo,CalvinJ

Intestinal Crypts Assume the Fetal Position in Response to Injury.

肠隐窝因受伤而采取胎儿位置。

• DOI: 10.1016/j.stem.2018.07.013
• 发表时间: 2018
• 期刊: Cell stem cell
• 影响因子: 23.9
• 作者: Pont,AdamR;Yan,KelleyS
• 通讯作者: Yan,KelleyS