Generation of trisomy 21 induced pluripotent stem cells

21 三体诱导多能干细胞的产生

基本信息

批准号：
7739054
负责人：
ANITA BHATTACHARYYA
金额：
$ 21.21万
依托单位：
UNIVERSITY OF WISCONSIN-MADISON
依托单位国家：
美国
项目类别：
财政年份：
2009
资助国家：
美国
起止时间：
2009-09-30 至 2011-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7739054
关键词：
Affect Alzheimer&apos s Disease Biomanufacturing Brain Cell Line Cell model Cells Characteristics Chromosomes Chromosomes, Human, Pair 21 Clinical Communities Congenital Heart Defects Coupled Craniofacial Abnormalities Data Defect Development Developmental Process Down Syndrome Embryo Environment Equipment Evaluation Fibroblasts Generations Genetic Goals Housing Human Immune system Impairment Individual Knowledge Lead Life Mental Retardation Mental Retardation and Developmental Disabilities Research Centers Mission Modeling Molecular Nerve Degeneration Nervous system structure Neurologic Neuronal Differentiation Neurons Neurosciences Non-Viral Vector Organ Pluripotent Stem Cells Predisposition Process Prosencephalon Psyche structure Public Health Reagent Reporting Research Research Personnel Research Priority Resources Services Source Stem Cell Research Stem cells Synapses System Testing Tissues Trisomy Universities Validation Viral Wisconsin Work base cell type developmental disease embryonic stem cell experience human disease induced pluripotent stem cell innovation interest leukemia mouse model neurodevelopment neurogenesis programs public health relevance relating to nervous system research study success

项目摘要

DESCRIPTION (provided by applicant): Down Syndrome (DS), or trisomy 21, is the most common genetic developmental disorder that leads to mental retardation. Mouse models have implicated reduced neurogenesis and faulty synaptic development as important contributors to the mental impairment characteristic of DS. While mouse models are crucial, they cannot explain all the complexities of human brain development making it important to examine the effects of trisomy 21 in the context of human cells. Human neural development in DS has not been well studied. An innovative way to study the development of particular cell types is through the use of human pluripotent stem cells. This exploratory proposal aims to take advantage of recent reports of induced pluripotent stem cells (iPS cells) to create Down syndrome-specific pluripotent stem cells to facilitate analysis of human neural development. The first aim of this proposal is to induce pluripotent stem cells from human fibroblasts that carry the trisomy 21. The second aim will exploit this new resource by testing the feasibility of differentiating these trisomy 21 iPS cells into functional forebrain neurons. The establishment of this human trisomy 21 neuronal culture paradigm will enable studies dissecting the molecular mechanisms of at least three important research priorities in Down syndrome: neurogenesis, synapse development and function, and neurodegeneration. PUBLIC HEALTH RELEVANCE: As the most common genetic cause of mental retardation, Down syndrome is a public health concern. The proposed research will create a new model of Down syndrome to advance the study of Down syndrome neuropathophysiology. The aims of this proposal include making Down syndrome-specific human pluripotent stem cells from non-embryonic sources.

描述（由申请人提供）：唐氏综合症（DS）或第21三体综合征，是导致智力低下的最常见遗传发育障碍。小鼠模型暗示着神经发生和突触发育故障，是DS心理障碍特征的重要因素。尽管小鼠模型至关重要，但它们无法解释人脑发育的所有复杂性，因此在人类细胞的背景下检查三体性21的影响很重要。 DS中的人类神经发育尚未得到很好的研究。研究特定细胞类型的开发的一种创新方法是使用人多能干细胞。该探索性建议旨在利用诱导多能干细胞（IPS细胞）的最新报道，以创建唐氏综合征特异性多能干细胞，以促进人类神经发育的分析。该建议的第一个目的是诱导携带三体性21的人类成纤维细胞的多能干细胞。第二个目标将通过测试将这些三体三体21 IPS细胞分化为功能性前脑神经元的可行性来利用这一新资源。建立这种人类三体性21神经元培养范式将使研究能够研究唐氏综合症至少三个重要研究优先级的分子机制：神经发生，突触发育和功能以及神经变性。公共卫生相关性：作为智力低下的最常见遗传原因，唐氏综合症是公共卫生的关注。拟议的研究将创建一种新的唐氏综合症模型，以推动唐氏综合症神经病生理学的研究。该提案的目的包括从非胚胎来源制成唐氏综合症特异性人多能干细胞。