Otic Guidance

耳部指导

• 批准号: 10519111
• 负责人: Stefan Heller
• 金额: $ 15.74万
• 依托单位: STANFORD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-12-01 至 2024-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10519111
• 关键词: Affect; Appearance; Applications Grants; Awareness; Biopsy; Cell Differentiation process; Cell Lineage; Cell Separation; Cells; Computer Analysis; Computer Models; Data; Data Analyses; Dissociation; Drug Evaluation; Drug Screening; Ectoderm; Epithelial Cells; Epithelium; Failure; Gene Expression; Generations; Goals; Hair Cells; Individual; Laboratories; Labyrinth; Location; Methanol; Methods; Modification; Mus; Pathway interactions; Patients; Phenotype; Pluripotent Stem Cells; Population; Protocols documentation; Research; Research Proposals; Sensory; Sensory Hair; Signal Pathway; Signal Transduction; Supporting Cell; Technology; Validation; Variant; Vesicle; cell type; comparative; embryonic stem cell; experimental study; improved; inhibitor; inner ear development; inner ear diseases; placodal ectoderm; preservation; sample fixation; single-cell RNA sequencing; stem cells; three dimensional cell culture; transcriptomics

Project Summary / Abstract The first aim of this research proposal is to use single-cell transcriptomics to describe the changes in gene expression that happen during otic guidance from pluripotent stem cells. It builds on known principles of inner ear development and utilizes single-cell RNA-Seq and computational modeling for extracting the differentiation pathway of cells towards non-neural ectoderm, pre-placodal ectoderm, and ultimately otic induction and the sensory hair cell lineage. In a second aim, it is proposed to comparatively investigate the distinct steps when otic guidance from embryonic stem cells fails, which is a common problem. The generation of inner ear cells from embryonic stem cells is an unreliable enterprise and has hampered research for more than a decade. Computational comparisons of gene expression changes in successfully guided inner ear lineage cells with lineages that stray from otic differentiation will result in the identification of specific signaling pathways that contribute to cell differentiation failures. Based on computational modeling, testable hypotheses will be generated and experimentally validated. The ultimate goal of the proposed research is the elimination of experimental variations of otic guidance from stem cells towards establishing a reliable otic guidance protocol that can be widely utilized by many laboratories.

项目摘要/摘要