Regulation of Human Embryonic Stem Cells by Wnts

Wnts 对人胚胎干细胞的调控

• 批准号: 7664938
• 负责人: Randall Todd Moon
• 金额: $ 33.56万
• 依托单位: UNIVERSITY OF WASHINGTON
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/7664938
• 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信号通路调节胚胎的细胞增殖，分化，极性和行为 发育，成年干细胞以及癌症和其他疾病状态。因此，Wnt是合理的 候选人在人类胚胎干细胞（HESC）的正常生物学中扮演重要角色和 改变体外培养的hESC的增殖和分化。至少两个Wnt信号通路 存在于脊椎动物中，Wnt/li-catenin途径通过明确的定义控制基因表达 途径，以及一个或多个可以拮抗Wnt/b-catenin途径的“非经典”途径。在 各种干细胞Wnt/li-catenin途径与控制自我更新，增殖有关 和分化。相反，hESC中非规范途径的存在或功能没有 报道了。该项目的总体目标是检验以下假设：不同的Wnt信号通路 在功能上参与了hESC的体外增殖和分化，以阐明不同的 信号传导机制，并利用这些见解在体外引导hESC分化。具体 Aimsare： 目标1。询问hESC中不同的Wnt信号通路 目标2。miRNA对hESC中Wnt途径的调节 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了解调节的机制 hESC通过Wnt信号传导，尤其是关于Wnt在HESC增殖中的作用的hESC 和运动。这些发现可以被利用以在体外操纵hESC，最终的目标 生成可以对人类疾病产生治疗影响的hESC分化方案。