Regulation of Human Embryonic Stem Cells by Wnts

Wnts 对人胚胎干细胞的调控

• 批准号: 7356488
• 负责人: Randall Todd Moon
• 金额: $ 30.86万
• 依托单位: UNIVERSITY OF WASHINGTON
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-08-01 至 2012-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7356488
• 关键词: Affect; Antibodies; Arts; Behavior; Biological Assay; Biology; Butyrates; Cardiac Myocytes; Cell Proliferation; Cells; Collaborations; Colorectal; Complex; Data; Data Set; Disease; Embryonic Development; Gene Expression; Gene Expression Profile; Genome; Goals; Growth Factor; Human Development; In Situ Hybridization; In Vitro; Link; Malignant Neoplasms; MicroRNAs; Microfluidics; Molecular Profiling; Monitor; Pathway interactions; Pilot Projects; Play; Population; Positioning Attribute; Protocols documentation; Reading; Regulation; Reporter; Reporting; Research; Research Personnel; Role; Signal Pathway; Signal Transduction; Staining method; Stains; Stem cells; Technology; Testing; Therapeutic; Vertebrates; adult stem cell; butyrate; cell motility; cell type; experience; human disease; human embryonic stem cell; insight; new technology; novel; programs; response; self-renewal

Wnt signaling pathways regulate cell proliferation, differentiation, polarity, and behavior in embryonic development, in adult stem cells, and in cancers and other disease states. Wnts are therefore reasonable candidates for playing essential roles in the normal biology of human embryonic stem cells (hESCs) and for altering the proliferation and differentiation of hESCs cultured in vitro. At least two Wnt signaling pathways exist in vertebrates, the Wnt/li-catenin pathway that controls gene expression through a well-defined pathway, and one or more "non-canonical" pathways that can antagonize the Wnt/B-catenin pathway. In various stem cells the Wnt/li-catenin pathway has been implicated in controlling self-renewal, proliferation, and differentiation. In contrast, the existence or functions of the non-canonical pathways in hESCs have not been reported. The overall goal of this project is to test the hypothesis that distinct Wnt signaling pathways are functionally involved in the in vitro proliferation and differentiation of hESCs, to elucidate the different mechanisms of signaling, and to leverage these insights to direct hESC differentiation in vitro. The specific aimsare: Aim 1. Interrogating distinct Wnt signaling pathways in hESC Aim 2. Regulation of Wnt pathways in hESCs by miRNAs Aim 3. Responses of hESCs to gradients of Wnt-3a and Wnt-5a ^ Collectively, the proposed studies will lend further insight into the mechanisms underlying the regulation of hESCs by Wnt signaling, particularly with regards to the role of Wnts in hESC proliferation, differentiation and motility. These findings can be exploited to manipulate hESCs in vitro with the eventual goal of generating protocols for hESC differentiation that can have therapeutic impact on human disease.

Wnt 信号通路调节胚胎细胞增殖、分化、极性和行为 成体干细胞以及癌症和其他疾病状态的发育。因此 Wnt 是合理的 在人类胚胎干细胞（hESC）的正常生物学中发挥重要作用的候选者 改变体外培养的 hESC 的增殖和分化。至少两条Wnt信号通路 存在于脊椎动物中的 Wnt/li-catenin 通路通过明确定义的控制基因表达 途径，以及可以拮抗Wnt/B-连环蛋白途径的一种或多种“非经典”途径。在 Wnt/li-catenin 通路与多种干细胞的自我更新、增殖、 和差异化。相比之下，hESC 中非经典途径的存在或功能尚未被证实。 被举报。该项目的总体目标是检验以下假设：不同的 Wnt 信号通路 在功能上参与 hESC 的体外增殖和分化，以阐明不同的 信号传导机制，并利用这些见解来指导 hESC 体外分化。具体的 目标是： 目标 1. 探究 hESC 中不同的 Wnt 信号通路 目标 2. miRNA 对 hESC 中 Wnt 通路的调节 目标 3. hESC 对 Wnt-3a 和 Wnt-5a 梯度的响应 ^ 总的来说，拟议的研究将进一步深入了解监管的机制 通过 Wnt 信号转导研究 hESC，特别是 Wnt 在 hESC 增殖、分化中的作用 和动力。这些发现可用于体外操纵 hESC，最终目标是 生成可对人类疾病产生治疗影响的 hESC 分化方案。