Mapping the Trajectory of Cell Fate Transitions

绘制细胞命运转变的轨迹

• 批准号: 8295281
• 负责人: Kenneth David Birnbaum
• 金额: $ 30.54万
• 依托单位: NEW YORK UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-06-19 至 2016-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8295281
• 关键词: Address; Adult; Animals; Behavior; Biological Models; Cell division; Cell model; Cell physiology; Cells; Clear Cell; Complex; Confocal Microscopy; Development; Developmental Biology; Disease; Epigenetic Process; Equipment and supply inventories; Exhibits; Gene Expression Profile; Genes; Germ Cells; Goals; Hour; Human; Image; Incidence; Learning; Libraries; Light; Limb structure; Maps; Mediating; Memory; Methods; Modeling; Modification; Molecular; Morphology; Natural regeneration; Optics; Organ; Organism; Pattern Formation; Plants; Plastics; Polycomb; Process; Property; Proteins; Recording of previous events; Regenerative Medicine; Research; Resolution; Role; Specific qualifier value; Staging; Stem cells; System; Techniques; Testing; Therapeutic; Tissues; Transcript; Work; cell dedifferentiation; cell injury; cell type; cellular imaging; flexibility; improved; in vivo; innovation; insight; novel; novel strategies; pluripotency; prevent; regenerative; regenerative therapy; response to injury; single cell analysis; tool; trait

DESCRIPTION (provided by applicant): Organisms capable of dramatic regeneration maintain adult cells that have the flexibility, or plasticity, to change their fate. This feature enables thm build replacement parts, like organs or limbs, to recover from damage or disease. Previous work on the project and other studies have revealed a broad propensity for specialized cells to display some properties of stem cells; they give rise to new cell types in response to injury. The dynamic changes that cells undergo during the transition from one fate to another could reveal the mechanisms that cells employ to enable them to switch their fates. Such insights will reveal basic features of cellular plasticity that could improve regeneration therapy in human cells. However, due to limitations in analyzing the global status of regenerating cells in vivo, little is known about how cells make the traversal from one state to another. The experimental plan proposes to provide a comprehensive view of cells as they transition to new fates during regeneration. The study utilizes plants because the model system provides a rare opportunity to model cellular plasticity. In addition, the mechanisms that regulate plasticity are well conserved across plants and animals and the plant's adept ability to regenerate will illustrate the full potential of cells to change their identity. The proposal takes advantage of a powerful model system that permits continual imaging of regenerating tissue and the analysis of the transcriptional contents of single cells as they traverse fates. This system includes an inventory of active genes for each cell fate, permitting quantitative analyses to track the complex identity of cells as they regenerate. Thus, the complete analysis will generate a model of the trajectory of regenerating cells in order to address basic questions about regeneration: What is the origin of the highly plastic cells that participate in regeneration? Do regenerating cells show proliferative behavior that resembles stem cells? Do fate transitions require losing all identity and reaching a "ground" state or younger developmental stage (dedifferentiation)? Or, do cells traverse directly to new fates? The results will point to processes that can be targeted to make regeneration more efficient. The innovation of profiling the complete transcriptional dynamics of cells and projecting them onto images of regenerating tissue is widely applicable to many developmental model systems. Thus, overall, the proposed work has broad impact on the field of regeneration. PUBLIC HEALTH RELEVANCE: One important goal in therapeutic regeneration is to enhance the ability of existing cells to replace damaged cells. Despite their differences, plants and animals share mechanisms that control a cell's ability to switch identities. The goal of the projec is to use a powerful system in the highly regenerative plant to understand how a cell can change its identity with the aim to provide insights for new approaches in regenerative medicine.

描述（由申请人提供）：能够戏剧性再生的生物维护具有柔韧性或可塑性的成年细胞，以改变其命运。此功能使该功能可以构建替换零件，例如器官或四肢，从损害或疾病中恢复。该项目和其他研究的先前工作表明，专门细胞表现出某些特性的干细胞倾向。它们会导致新的细胞类型，以应对伤害。细胞在从一个命运到另一种命运的过渡过程中发生的动态变化可能揭示了细胞使它们能够切换命运的机制。这种见解将揭示细胞可塑性的基本特征，这些特征可以改善人类细胞的再生疗法。但是，由于分析体内再生细胞的全局状态的局限性，几乎没有 知道细胞如何使遍历从一个状态到另一个状态。 实验计划建议在再生期间过渡到新命运时，为细胞提供全面的看法。该研究使用植物，因为模型系统提供了建模细胞可塑性的罕见机会。此外，调节可塑性的机制在动植物之间是良好的保守，并且该植物的再生能力将说明细胞改变其身份的全部潜力。该提案利用了强大的模型系统，该系统允许对再生组织的持续成像以及在遍历命运时的转录内容物的分析。该系统包括每个细胞命运的活性基因清单，允许定量分析以跟踪细胞再生时的复杂身份。因此，完整的分析将产生再生细胞轨迹的模型，以解决有关再生的基本问题：参与再生的高度塑料细胞的起源是什么？再生细胞是否显示出类似于干细胞的增殖行为？命运过渡是否需要失去所有身份并达到“地面”状态或以上的发展阶段（去分化）？还是，细胞会直接遍历新的命运吗？ 结果将指出可以针对的过程，以提高再生的效率。分析细胞的完整转录动力学并将它们投射到再生组织的图像上的创新广泛适用于许多发展模型系统。因此，总的来说，拟议的工作对再生领域产生了广泛的影响。 公共卫生相关性：治疗再生的一个重要目标是增强现有细胞替代受损细胞的能力。尽管它们的差异差异，但动植物具有控制细胞切换身份能力的机制。 ProJec的目的是在高度再生植物中使用强大的系统来了解细胞如何改变其身份，以提供有关再生医学新方法的见解。