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Dissecting single cell dynamics that coordinate neural crest migration and diversification

剖析协调神经嵴迁移和多样化的单细胞动力学

基本信息

批准号：
10590577
负责人：
Qing Nie
金额：
$ 55.24万
依托单位：
UNIVERSITY OF CALIFORNIA-IRVINE
依托单位国家：
美国
项目类别：
财政年份：
2021
资助国家：
美国
起止时间：
2021-04-01 至 2026-03-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10590577
关键词：
Actins Adhesions Adhesives Behavior Biography Cadherins Cell Adhesion Cell Communication Cell Differentiation process Cell Lineage Cell physiology Cell-Cell Adhesion Cells Cephalic Complex Computer Models Computing Methodologies Congenital Abnormality Cytoskeleton Data Data Set Defect Development Disease Dorsal Embryo Embryonic Development Emigrations Environment Epithelium Event First Pharyngeal Arch Focal Adhesions Gene Combinations Gene Expression Gene Expression Profiling Genes Genetic Models Heterogeneity Image Individual Label Location Malignant Neoplasms Mandible Maps Mesenchymal Methods Monitor Movement Mutation Neural Crest Neural Crest Cell Organ Pattern Peripheral Nervous System Pigmentation physiologic function Pigments Process Proteins Publishing Regenerative Medicine Regulation Reporter Research Role Skeleton Sorting Specific qualifier value System Testing Therapeutic Time Tissues WNT Signaling Pathway Zebrafish cell fate specification cell motility cell type craniofacial cranium gene function gene regulatory network imaging platform in vivo in vivo imaging insight intercellular communication interdisciplinary approach live cell imaging melanoma migration mutant novel novel strategies population migration programs regenerative therapy response single-cell RNA sequencing skeletal spatiotemporal tool trafficking transcriptome sequencing

项目摘要

RESEARCH SUMMARY Embryonic development involves the formation of functional organs comprised of many different cell types, which often originate from different locations. Thus cell migration and differentiation must be tightly coordinated, but are typically studied as independent processes. Here we use a combination of gene expression profiling in single cells, zebrafish genetics and computational models to test the hypothesis that migration and differentiation are coordinated. This coordination requires specific regulators of cell adhesion dynamics and cell-cell signaling. We focus on neural crest cells, a transient embryonic population that migrates throughout the body to give rise to a huge range of different fates. One barrier to studying this problem has been the limited number of tools available to detect transitional states in individual cells as they differentiate and tie this to their migratory behaviors in a precise and quantitative manner. Here we develop new approaches for profiling gene expression in single cells from known locations and tracking their movements in vivo. We will analyze how genes required for cell adhesion and cell-cell signaling influence these processes, and use computational models to predict key features of neural crest cell responses. We expect that such a multidisciplinary approach will reveal insights into the mechanisms that integrate cell migration and fate.

研究综述胚胎发育涉及到由许多器官组成的功能器官的形成。不同的细胞类型，它们通常来自不同的位置。因此，细胞迁移和分化必须紧密协调，但通常作为独立的研究流程.在这里，我们使用单细胞中基因表达谱的组合，斑马鱼遗传学和计算模型来测试迁移和差异是协调的。这种协调需要特定的细胞调节因子粘附动力学和细胞-细胞信号传导。我们专注于神经嵴细胞，一个短暂的胚胎人口迁移到整个身体，产生了巨大的范围，不同的命运研究这个问题的一个障碍是工具的数量有限可用于检测单个细胞分化时的过渡状态，并将其与它们的迁徙行为进行精确的定量分析。在这里，我们开发新的用于在来自已知位置的单细胞中分析基因表达的方法，追踪它们在体内的活动我们将分析细胞粘附所需的基因和细胞间信号传导影响这些过程，并使用计算模型，预测神经嵴细胞反应的关键特征。我们期待这样一个多学科的方法将揭示细胞整合机制的见解，迁徙与命运