Embryonic Stem Cells and Neural Crest Plasticity

胚胎干细胞和神经嵴可塑性

• 批准号: 7211027
• 负责人: YAN ZHOU
• 金额: $ 8.15万
• 依托单位: UNIVERSITY OF SOUTHERN CALIFORNIA
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-06-05 至 2009-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7211027
• 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

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）：干细胞生物学将在因疾病或损伤而受损的组织和器官的修复和再生中发挥重要作用。因此，更好地理解用于调节干细胞祖细胞群维持的分子事件，以及识别决定干细胞进行谱系特异性分化的信号通路将仍然是生物医学研究中的重要问题。神经嵴细胞是多能干细胞，有助于形成整个胚胎的多种组织。由于缺乏体外培养系统，哺乳动物神经嵴命运的确定受到阻碍。釉原蛋白除了是牙釉质形成所必需的结构蛋白之外，似乎还充当细胞规范中的信号分子。釉原蛋白剪接产物已被证明可以发挥特定的信号传导作用，并在体外和体内诱导细胞分化的变化。我们认为牙釉蛋白是一种信号分子，能够调节胚胎干细胞向神经嵴细胞分化，并随后沿着成骨谱系分化。使用胚胎干细胞，我们将通过执行以下具体目标来检验这一假设： I) 使用功能丧失和功能获得实验来确定牙釉蛋白在指导胚胎干 (ES) 细胞分化为颅脑细胞方面的生物学功能神经嵴（CNC）样多能祖细胞； II) 使用组织重组策略来检查颅神经嵴（如 ES 细胞衍生的多能祖细胞）分化为牙源性谱系的潜力。胚胎干细胞成功衍生出颅神经嵴样多能祖细胞，将为体外神经嵴细胞谱系分析提供新工具。这些具体目标的结果将用于优化维持干细胞群的策略，同时提高我们刺激颅面和骨骼组织中组织和器官缺陷修复和再生所需的细胞特异性谱系发育的能力。