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Fine-scale Spatiotemporal Mapping of Cellular Regulatory Networks Directing Heart Development

指导心脏发育的细胞调节网络的精细时空绘图

基本信息

批准号：
10437807
负责人：
Neil C Chi
金额：
$ 62.62万
依托单位：
UNIVERSITY OF CALIFORNIA, SAN DIEGO
依托单位国家：
美国
项目类别：
财政年份：
2020
资助国家：
美国
起止时间：
2020-08-01 至 2025-07-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10437807
关键词：
Accounting Adult Animals Behavior Biological Assay Cardiac Cardiovascular system Cells Chromatin Communities Computer Analysis Data Set Development Embryonic Development Event Family Fluorescent in Situ Hybridization Gene Expression Profile Genes Genetic Transcription Genetic study Goals Heart Human In Situ In Vitro Label Lead Maps Mediating Mesoderm Modeling Molecular Monitor Morphogenesis Mus Mutation Newborn Infant Patient-Focused Outcomes Patients Phenotype Physicians Population Population Heterogeneity Process Regulator Genes Regulatory Pathway Research Role Societies Source Specific qualifier value Structure Systems Biology Transgenic Organisms Validation base cardiogenesis cell type congenital anomaly congenital heart disorder gene network gene regulatory network human pluripotent stem cell improved insight multidisciplinary patient population progenitor reconstruction single cell analysis spatiotemporal stem cell model stem cells transcriptome sequencing translational framework

项目摘要

Project Summary Congenital Heart Disease is the most common congenital anomaly in newborn babies, accounting for one third of all major congenital anomalies. Despite recent congenital heart disease genetic studies highlighting the critical role of cardiac transcriptional and chromatin regulators during heart development, our understanding of how these developmental regulators interact to create the dynamic gene regulatory networks that mediate heart development remains to be fully elucidated. Thus, we propose to define and assay the cardiovascular developmental regulators and their gene regulatory networks that direct the development of the vast array of cardiovascular cell types creating the mammalian heart. To achieve this goal, a multi-disciplinary experimental and computational systems biology approach will be implemented to: (1) elucidate gene regulatory networks that establish the cardiogenic cellular hierarchy of the developing mammalian heart, (2) investigate the spatiotemporal organization of the cardiogenic cellular hierarchy during mouse embryogenesis and heart morphogenesis and (3) functionally examine how distinct cardiovascular developmental sources create specific cardiovascular lineages contributing to the developing heart.

项目摘要先天性心脏病是新生儿最常见的先天性异常，占三分之一所有重大先天性异常的原因尽管最近的先天性心脏病遗传研究强调，心脏转录和染色质调节因子在心脏发育过程中的关键作用，我们对这些发育调节因子如何相互作用，形成动态的基因调控网络，心脏发育仍有待充分阐明。因此，我们建议定义和测定心血管发育调节因子及其基因调控网络，指导了大量的心血管细胞类型创造哺乳动物心脏。为了实现这一目标，多学科实验和计算系统生物学的方法将实施：（1）阐明基因调控网络建立发育中哺乳动物心脏的心源性细胞等级，（2）研究小鼠胚胎发育和心脏中心源性细胞等级的时空组织形态发生和（3）功能检查不同的心血管发育来源如何产生特定的心血管谱系有助于心脏的发育。