TR&D1: Stem Cell and Induced Pluripotent Stem Cell Resources (Pages 116-134)

TR

• 批准号: 8529766
• 负责人: J. Michael Pierce
• 金额: $ 285.93万
• 依托单位: UNIVERSITY OF GEORGIA
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-08-01 至 2018-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8529766
• 关键词: Area; Beds; Biochemical; Biological Markers; Biological Models; Cardiac; Cardiovascular system; Cell Differentiation process; Cell Line; Cell Lineage; Cell model; Cells; Collaborations; Communities; Congenital Disorders; Development; Disease; Disease model; Embryonic Development; Enzymes; Funding; Glycobiology; Glycolipids; Glycoproteins; Human; Human Resources; Lead; Liver; Mediating; Methods; Modeling; Molecular; Neural Crest; Pancreas; Pathway interactions; Patients; Pluripotent Stem Cells; Polysaccharides; Process; Production; Quality Control; Regulation; Research Personnel; Resources; Sampling; Stem cells; Structure; Subfamily lentivirinae; Technology; Testing; Tetracyclines; Transcript; Validation; Work; base; cell type; congenital muscular dystrophy; embryonic stem cell; glycosylation; human disease; human embryonic stem cell; induced pluripotent stem cell; insight; knock-down; loss of function; overexpression; relating to nervous system; research study; small hairpin RNA; stem cell technology; success; technology development; tool; tool development; Area; Beds; Biochemical; Biological Markers; Biological Models; Cardiac; Cardiovascular system; Cell Differentiation process; Cell Line; Cell Lineage; Cell model; Cells; Collaborations; Communities; Congenital Disorders; Development; Disease; Disease model; Embryonic Development; Enzymes; Funding; Glycobiology; Glycolipids; Glycoproteins; Human; Human Resources; Lead; Liver; Mediating; Methods; Modeling; Molecular; Neural Crest; Pancreas; Pathway interactions; Patients; Pluripotent Stem Cells; Polysaccharides; Process; Production; Quality Control; Regulation; Research Personnel; Resources; Sampling; Stem cells; Structure; Subfamily lentivirinae; Technology; Testing; Tetracyclines; Transcript; Validation; Work; base; cell type; congenital muscular dystrophy; embryonic stem cell; glycosylation; human disease; human embryonic stem cell; induced pluripotent stem cell; insight; knock-down; loss of function; overexpression; relating to nervous system; research study; small hairpin RNA; stem cell technology; success; technology development; tool; tool development

This Center is dedicated to the development of technologies and tools for the identification and characterization of glycan structures and transcripts associated with cellular glycoproteins and glycolipids. As a test-bed for the further development of glycomic technologies and tools, studies will again focus on the characterization of human pluripotent stem cells, including embryonic stem cells (hESCs) and induced pluripotent stem cells (iPSCs). A range of differentiated cell lineages derived from stem cells will be incorporated into this analysis. This biological model is ideal as a test-bed for glycomics technologies and tool development because it offers a diverse range of glycan structures and challenges due to the diversity in cell types that can be generated. These studies will offer new insights into human embryonic development and will lead to the identification of new biomarkers for stem cell characterization. A major strength of this TR&D has been its success in generating pure, well-characterized cell types from hESC and hiPSCs. For example, we routinely produce neural, liver, pancreatic and cardiac lineages that are suitable for downstream analysis. The first method for direct differentiation of neural crest stem cells from pluripotent cells [1] was developed as part of the Center's previous round of funding. Additional cardiovascular lineages are also being developed to increase the diversity of cells to be analyzed by other TR&Ds'and to enhance glycan complexity that will be encountered. In this competitive renewal, we propose to extend our previous work and also include a new emphasis on human iPSC models for glycosylation-related disease. Understanding the basis of these diseases represents a major challenge and an area that is largely underexplored and poorly understood. Using iPSC-reprogramming technology, we propose to generate panels of fully validated cell lines that can serve as models for human congenital disorders of glycosylation (CDG) and congenital muscular dystrophy (CMD). This will serve to provide valuable resources for a large number of investigators and to create a truly challenging test-bed for glycomics technology development. Another major new component of this TR&D is the inclusion of Dr. Richard Steet as co-investigator. Dr. Steet will bring his broad expertise in the area of congenital glycosylation disorders to this effort and will be primarily responsible for the biochemical validation of the resulting cell lines. Dr. Steet will also coordinate the interactions between many DBP collaborators and personnel within this TR&D.

该中心致力于开发技术和工具，用于鉴定和表征与细胞糖蛋白和糖脂相关的聚糖结构和转录本。作为用于进一步开发糖技术和工具的测试床，研究将再次集中在人类多能干细胞（包括胚胎干细胞（HESC）和诱导多能干细胞（IPSC））的表征上。从干细胞中得出的一系列分化细胞谱系将纳入该分析中。该生物学模型是糖基质技术和工具开发的测试床，因为它由于可以生成的细胞类型的多样性而提供了各种各样的聚糖结构和挑战。这些研究将为人类胚胎发育提供新的见解，并将导致对干细胞表征的新生物标志物的鉴定。该TR＆D的主要优势是它成功地从HESC和HIPSC生成纯净，良好的细胞类型。例如，我们通常会产生适合下游分析的神经，肝，胰腺和心脏谱系。作为中心上一轮资助的一部分，开发了从多能细胞直接分化神经rest干细胞[1]的第一种方法。还开发了其他心血管谱系，以增加其他TR＆DS'要分析的细胞多样性，并增强将遇到的聚糖复杂性。 在这种竞争性更新中，我们建议扩展我们以前的工作，还包括对与糖基化相关疾病的人IPSC模型的新重点。理解这些疾病的基础是一个主要挑战，并且在很大程度上没有被忽视且理解不足的领域。使用IPSC编程技术，我们建议生成完全验证的细胞系的面板，这些细胞系可以用作人类糖基化（CDG）和先天性肌肉营养不良（CMD）的模型。这将为大量调查人员提供宝贵的资源，并为糖胶质技术开发创建真正具有挑战性的测试床。该TR＆D的另一个主要新组成部分是Richard Steet博士作为共同研究员。 Steet博士将把他在先天性糖基化障碍领域的广泛专业知识带入这项工作，并将主要负责对所得细胞系的生化验证。 Steet博士还将协调此TR＆D中许多DBP合作者与人员之间的互动。