REGULATION OF ABCG2 IN RETINAL STEM CELLS/PROGENITORS

ABCG2 在视网膜干细胞/祖细胞中的调节

• 批准号: 8168362
• 负责人: Sumitra Bhattacharya
• 金额: $ 19.84万
• 依托单位: UNIVERSITY OF NEBRASKA MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-07-01 至 2011-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8168362
• 关键词: ABCG2 gene; Binding; Cell Differentiation process; Cells; Characteristics; Computer Retrieval of Information on Scientific Projects Database; DNA; Dyes; Fluorescence-Activated Cell Sorting; Funding; Grant; Indium; Institution; Integral Membrane Protein; Maintenance; Mediating; Molecular; Phenotype; Population; Regulation; Repression; Research; Research Personnel; Resources; Retinal; Side; Signal Transduction; Small Interfering RNA; Source; Stem cells; United States National Institutes of Health; base; in vivo; notch protein; progenitor; promoter; relating to nervous system; research study; retinal progenitor cell

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. One of the emerging universal characteristics of stem cells/progenitors, including neural and retinal stem cells, is the preferential expression of ABCG2, a half transporter belonging to ATP-binding cassette (ABC) superfamily of transmembrane proteins. These transporters mediate efflux of a broad spectrum of substrates and their ability to preferentially exclude DNA intercalating dye, Hoechst 33342, is regarded to be the molecular basis for the enrichment of stem cells as side population (SP) of cells by fluorescence activated cell sorting. The decline of expression of ABCG2 with retinal differentiation suggests that ABCG2 expression is involved in the maintenance of stem cells, and this has been supported by perturbation of expression by transduction and by siRNA repression, which showed that the magnitude of the SP corresponded to the level of ABCG2 expression and maintenance of stem cell phenotype. We have hypothesized that ABCG2 is regulated through Notch signaling. Our preliminary studies have shown that Notch1 and ABCG2 colocalize, and that inhibition of Notch results in decreased expression of ABCG2 and cell differentiation. We also have evidence that activation of ABCG2 by Notch is mediated through CSL elements in the ABCG2 promotor. These results will be verified by in vivo experiments.

该子项目是利用该技术的众多研究子项目之一 资源由 NIH/NCRR 资助的中心拨款提供。子项目及 研究者 (PI) 可能已从 NIH 的另一个来源获得主要资金， 因此可以在其他 CRISP 条目中表示。列出的机构是 对于中心来说，它不一定是研究者的机构。 干细胞/祖细胞（包括神经干细胞和视网膜干细胞）的新兴普遍特征之一是 ABCG2 的优先表达，ABCG2 是属于跨膜蛋白 ATP 结合盒 (ABC) 超家族的半转运蛋白。 这些转运蛋白介导广谱底物的流出，并且它们优先排除 DNA 嵌入染料 Hoechst 33342 的能力被认为是通过荧光激活细胞分选将干细胞富集为细胞侧群 (SP) 的分子基础。 ABCG2 表达随着视网膜分化而下降，表明 ABCG2 表达参与干细胞的维持，并且这一点得到了转导扰动和 siRNA 抑制的支持，这表明 SP 的大小与干细胞的水平相对应。 ABCG2 表达和干细胞表型的维持。 我们假设 ABCG2 通过 Notch 信号传导进行调节。 我们的初步研究表明Notch1和ABCG2共定位，抑制Notch会导致ABCG2表达和细胞分化降低。 我们还有证据表明，Notch 对 ABCG2 的激活是通过 ABCG2 启动子中的 CSL 元件介导的。 这些结果将通过体内实验得到验证。