Probing the flexibility of G0

探索G0的灵活性

• 批准号: 10622658
• 负责人: Laura A Buttitta
• 金额: $ 34.35万
• 依托单位: UNIVERSITY OF MICHIGAN AT ANN ARBOR
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-08-01 至 2028-06-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10622658
• 关键词: Aging; Biological; Cell Cycle; Cell Cycle Inhibition; Cell Cycle Regulation; Cells; Development; Event; G0 Phase; Goals; Malignant Neoplasms; Metabolic; Molecular; Nutrient availability; Organ; Organism; Pathway interactions; Physiological; Process; Production; Series; Signal Transduction; Tissues; Work; daughter cell; flexibility; mature animal; response; tissue regeneration; tool; zygote

Project Summary/Abstract The cell cycle is an ordered series of molecular events in a cell leading to division and production of two daughter cells. This process is fundamental to the development of all multicellular organisms, which begin from a single cell, the fertilized egg. Equally important for proper development though, is the slowing or stopping of the cell cycle at the right places and times as cells, tissues and organs mature. In fact, the majority of cells in multicellular organisms spend most of their existence in non-proliferating states, often referred to as cellular quiescence or the G0 phase. In their non-dividing state, quiescent cells are metabolically active and carry out critical physiological functions in tissues and organs. Despite the importance of G0, most studies of cell cycle regulation have focused on rapidly dividing cells. Thus, it remains unclear how cells choose to enter G0 during development, and why some cells can choose to leave G0 and later re-enter the cell cycle in response to developmental signals, tissue damage, or nutrient availability while others cannot. It has become clear that there are multiple states of G0, some that are readily reversible, and others that are permanent. Different states of states may be controlled in distinct ways, both in the manner of cell cycle inhibition and in the pathways used to initiate exit. The goal of the work described here is to understand how the cell cycle machinery is controlled during the decision to exit the cell cycle, and how G0 can be modulated to be more or less reversible in different contexts. This work impacts a wide range of biological questions, as the proper control of quiescence is critical in development and tissue regeneration, but becomes disrupted in aging and cancer.

项目总结/摘要 细胞周期是细胞中一系列有序的分子事件，导致细胞分裂和产生两个 子细胞这个过程是所有多细胞生物发育的基础，这些生物开始于 一个细胞，受精卵然而，对于适当的发展同样重要的是， 在细胞、组织和器官成熟的正确位置和时间进行细胞周期。事实上，体内的大多数细胞 多细胞生物体在其存在的大部分时间中处于非增殖状态，通常被称为细胞增殖状态。 静止期或G 0期。在非分裂状态下，静止细胞具有代谢活性， 重要的生理功能。尽管G 0的重要性，大多数细胞周期的研究 调控集中在快速分裂的细胞上。因此，目前尚不清楚细胞如何选择进入G 0期， 以及为什么一些细胞可以选择离开G 0，然后重新进入细胞周期，以响应 发育信号，组织损伤或营养可用性，而其他人不能。很明显 存在G 0的多种状态，一些是容易可逆的，而另一些是永久的。不同 状态的状态可以以不同的方式控制，既可以以细胞周期抑制的方式，也可以以细胞周期抑制的方式。 用于启动退出的路径。这里描述的工作的目标是了解细胞周期是如何 在决定退出细胞周期的过程中，机器受到控制，以及如何调节G 0， 或多或少是可逆的这项工作影响了广泛的生物学问题，因为 适当控制静止状态对发育和组织再生至关重要，但在衰老过程中会受到破坏 和癌症