Mechanisms of Posterior Heart Field Development

心后区发育机制

基本信息

批准号：
10669667
负责人：
Neil C Chi
金额：
$ 51.22万
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 2024-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10669667
关键词：
Adult Affect Anterior Arrhythmia Cardiac Cardiac Myocytes Cardiovascular system Cells Characteristics Chemicals Circulation Cues Data Development Diagnosis Drug Screening Embryo Endothelium Epicardium Fibroblasts Functional disorder Genetic Genetic Transcription Heart Heart Diseases Human Individual Lateral Maps Mesoderm Molecular Myocardial Myocardium Pacemakers Pathway interactions Reporting Role Signal Pathway Signal Transduction Smooth Muscle Myocytes Source Specific qualifier value Structure System Therapeutic Translating Vertebrates WNT Signaling Pathway Zebrafish cardiogenesis cell type combinatorial congenital heart disorder disease-in-a-dish heart function human model human pluripotent stem cell in vivo notch protein progenitor regenerative therapy response segregation stem cells

Adult Affect Anterior Arrhythmia Cardiac Cardiac Myocytes Cardiovascular system Cells Characteristics Chemicals Circulation Cues Data Development Diagnosis Drug Screening Embryo Endothelium Epicardium Fibroblasts Functional disorder Genetic Genetic Transcription Heart Heart Diseases Human Individual Lateral Maps Mesoderm Molecular Myocardial Myocardium Pacemakers Pathway interactions Reporting Role Signal Pathway Signal Transduction Smooth Muscle Myocytes Source Specific qualifier value Structure System Therapeutic Translating Vertebrates WNT Signaling Pathway Zebrafish cardiogenesis cell type combinatorial congenital heart disorder disease-in-a-dish heart function human model human pluripotent stem cell in vivo notch protein progenitor regenerative therapy response segregation stem cells

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项目摘要

Project Summary: The heart consists of a multitude of diverse cardiac cell types, including but not limited to (chambered and non- chambered) cardiomyocytes, cardiac fibroblasts, epicardial cells, endothelial/endocardial cells and smooth muscle cells, which organize into distinct cardiac structures that coordinately regulate proper cardiac function and circulation throughout the body. Because loss or dysfunction of these cell types individually or combinatorially can lead to either adult or congenital heart diseases, increasing efforts have been recently devoted toward understanding how these diverse cardiovascular cell-types are created and function in order to develop potential human cardiac therapies. Such endeavors have illuminated not only the origins of many cardiac lineages but also key signaling cues and transcriptional regulators which in turn have been recently employed to efficiently direct various non-cardiac sources including human pluripotent stem cells and human fibroblasts into specific cardiac cell types for regenerative therapies. However, how cardiac cell types forming the cardiac inflow tract and the developmentally-related epicardium develop remains less certain in part due to their unclear origins. To shed light on these issues, we propose to discover the origins of these unique cardiac cell-types, which we posit derive from a common cardiac progenitor source, and then identify underlying signaling mechanisms that regulate their development. Toward this end, we will examine whether outlying Nkx2.5+ cardiac mesoderm is fated to become cardiac inflow tract cardiomyocytes and epicardial cells, identify signaling pathways that specify cardiac mesoderm into cardiac progenitors which create the cardiac inflow tract myocardium and epicardium and investigate whether these developmental mechanisms are conserved across vertebrates.

项目摘要：心脏由多种不同的心脏细胞类型组成，包括但不限于（室内和非 - 腔室）心肌细胞，心脏成纤维细胞，心外膜细胞，内皮/心内膜细胞和光滑肌肉细胞，它们分为不同的心脏结构，可协调地调节适当的心脏功能和整个身体的循环。因为这些单元类型的损失或功能障碍单独或组合可以导致成人或先天性心脏病，最近的努力越来越多致力于理解这些多样化的心血管细胞类型的创建并起作用发展潜在的人类心脏疗法。这样的努力不仅阐明了许多人的起源心脏谱系以及关键信号提示和转录调节因子又是最近用于有效指导各种非心脏来源，包括人类多能干细胞和人类成纤维细胞进入用于再生疗法的特定心脏细胞类型。但是，如何形成心脏细胞类型心脏流入道和与发育相关的心外膜发育不确定的部分原因是他们的起源不清楚。为了阐明这些问题，我们建议发现这些独特心脏的起源我们认为来自普通心脏祖细胞来源的细胞类型，然后识别基础调节其发展的信号传导机制。为此，我们将研究是否偏远 NKX2.5+心脏中胚层被命中成为心脏流入的心肌细胞和心外膜细胞，鉴定信号通路将心脏中胚层指定为心脏祖细胞，从而产生心脏流入道心肌和心外膜，并研究这些发展机制是否在跨越脊椎动物。