Using induced pluripotent stem cells to identify cellular phenotypes of autism

使用诱导多能干细胞识别自闭症的细胞表型

• 批准号: 8314027
• 负责人: Ricardo E. Dolmetsch
• 金额: $ 79.2万
• 依托单位: STANFORD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-09-30 至 2013-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8314027
• 关键词: Autistic Disorder; Biological; Biological Assay; Cell Line; Cells; Defect; Development; Disease; Etiology; Fibroblasts; Fingerprint; Genes; Genetic; Genotype; Goals; Harvest; Lead; Link; Measures; Mental disorders; Microscope; Morphology; Mutation; Neurons; Patients; Phenotype; Skin; base; human stem cells; in vitro Assay; induced pluripotent stem cell; migration; patch clamp; stem cell technology

Psychiatric diseases are devastating and poorly understood. The goal of this project is to identify the cell biological phenotypes that underlie autism and other psychiatric disorders, taking advantage of new developments in human stem cell technology. I propose to harvest skin fibroblasts from patients with autism, to reprogram these cells to generate induced pluripotent stem (iPS) cells, and to differentiate the iPS cells into neurons. I will then use a set of semi-automated in vitro assays to develop a phenotypic fingerprint for each cell line focusing on the developmental and functional phenotypes that are likely to lead to autism. We will use automated microscopes, cell sorters and semi-automated patch clamps to measure the differentiation, migration, survival, morphology, and excitability of neurons derived from patients. Finally, we will take advantage of the genetic information available for some autistic patients to determine whether deletion, duplication, or mutation of specific genes leads the phenotypes observed in the neurons from that patient. This approach has the potential to revolutionize our study of autism and other psychiatric disorders. It will allow us to link the phenotype and genotype of patients with the cell biological defects that give rise to disease. In addition, it will allow us to develop cell-based assays to both investigate the etiology of the disease and to find new treatments for these untreatable disorders.

精神疾病是毁灭性的，人们对其知之甚少。这个项目的目标是