Embryonic Stem Cells and Neural Crest Plasticity

胚胎干细胞和神经嵴可塑性

基本信息

批准号：
7436264
负责人：
YAN ZHOU
金额：
$ 8.06万
依托单位：
UNIVERSITY OF SOUTHERN CALIFORNIA
依托单位国家：
美国
项目类别：
财政年份：
2007
资助国家：
美国
起止时间：
2007-06-05 至 2010-11-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7436264
关键词：
Biological Models Biological Process Biomedical Research Cell Differentiation process Cell Lineage Cells Cellular biology Cephalic Code Data Defect Dental Cementum Dental Enamel Derivation procedure Development Disease ES Cell Line Embryo Embryonic Development Enamel Formation Event Exhibits Exons Family suidae Fibroblasts Gene Expression Genes Habits In Vitro Injury Jaw Laboratories Lead Maintenance Minerals Molecular Molecular Biology Molecular Profiling Multipotent Stem Cells Mus Muscle Neural Crest Neural Crest Cell Null Lymphocytes Organ Osteogenesis Pathway interactions Pattern Periodontal Ligament Periodontium Plastics Play Population Process Protein Family Proteins RNA Splicing Regenerative Medicine Regulation Reserve Cell Role Seminal Signal Pathway Signal Transduction Signaling Molecule Skeletal system Staging Stem cells Structural Protein System Testing Thinking Tissue Microarray Tissue Recombination Tissues Undifferentiated Work X Chromosome amelogenin bone cadherin-11 craniofacial embryonic stem cell gain of function homologous recombination human FZD3 protein improved in vivo loss of function member neuronal cell body novel progenitor receptor relating to nervous system repaired research study stem tissue regeneration tool

项目摘要

DESCRIPTION (provided by applicant): Stem cell biology will play a significant role in the repair and regeneration of tissues and organs damaged by disease or injury. Therefore a better understanding for the molecular events that serve to regulate maintenance of stem cell progenitor populations, as well as identifying the signaling pathways that determine stem cells into lineage specific differentiation will remain important issues in biomedical research. Neural crest cells are multipotent stem cells that contribute to a diverse array of tissues throughout the embryo. Determination of the fate of mammalian neural crest has been hindered by the lack of an in vitro culture system. Amelogenin besides being a structural protein indispensable for enamel formation appears to also function as a signaling molecule in cell specification. Amelogenin splicing products have been shown to exert specific signaling effects and to induce changes in cell differentiation both in vitro and in vivo. We propose that amelogenin is a signaling molecule capable of modulating embryonic stem cell differentiation to neural crest cell fate and subsequently along osteogenic lineage. Using embryonic stem cells, we will test this hypothesis by executing the following specific aims: I) Using loss-of-function and gain-of-function experiments to determine the biological function of amelogenin in directing embryonic stem (ES) cell differentiation to cranial neural crest (CNC)-like multipotent progenitor cells; II) Using a tissue recombination strategy to examine the potential of cranial neural crest like multipotent progenitor cells derived from ES cells to differentiate to odontogenic lineage. The successful derivation of cranial neural crestlike multipotent progenitor cells from embryonic stem cells will provide a new tool for cell lineage analysis of neural crest in vitro. The results from these specific aims will be used to optimize strategies for maintenance of stem cell populations while improving our ability to stimulate the development of cell specific lineages needed for the repair and regeneration of tissue and organ defects in craniofacial and skeletal tissues.

描述（由申请人提供）：干细胞生物学将在疾病或损伤受损的组织和器官的修复和再生中起重要作用。因此，对有助于调节干细胞祖细胞群体维持的分子事件的分子事件有更好的理解，以及确定确定干细胞谱系特定分化的信号传导途径将在生物医学研究中仍然是重要的问题。神经rest细胞是多能干细胞，在整个胚胎中有助于多种组织。缺乏体外培养系统阻碍了哺乳动物神经rest的命运的确定。除了是牙釉质形成必不可少的结构蛋白外，氨基蛋白素似乎也充当细胞规范中的信号分子。已显示氨基蛋白蛋白剪接产物可发挥特定的信号传导效应，并在体外和体内诱导细胞分化的变化。我们认为，氨基蛋白是一种信号分子，能够调节胚胎干细胞与神经rest细胞命运的分化，然后沿成骨谱系进行调节。使用胚胎干细胞，我们将通过执行以下特定目的来检验这一假设：i）使用功能丧失和功能获取实验来确定amelogoentin在指导胚胎茎（ES）细胞分化为颅神经crest（CNC）类似的多能祖细胞中的生物学功能； ii）使用组织重组策略来检查颅神经rest的潜力，例如衍生自ES细胞的多能祖细胞，以区分牙源性谱系。从胚胎干细胞中成功推导了颅神经风格的多能细胞，将为细胞谱系分析神经rest的体外分析提供新的工具。这些特定目标的结果将用于优化维持干细胞种群的策略，同时提高我们刺激颅面和骨骼组织中组织和器官缺陷所需的细胞特异性谱系发展的能力。