Probing the flexibility of G0

项目摘要/摘要 细胞周期是细胞内一系列有序的分子事件，导致两个分子的分裂和产生 子代细胞。这一过程是所有多细胞生物体发展的基础，它始于 一个单一的细胞，受精卵。然而，对于适当的发展来说，同样重要的是减缓或停止 随着细胞、组织和器官的成熟，细胞周期处于正确的时间和地点。事实上，大多数细胞在 多细胞生物生存的大部分时间都处于非增殖状态，通常被称为细胞 静止或G0阶段。在它们不分裂的状态下，静止的细胞代谢活跃，并进行 组织和器官中的重要生理功能。尽管G0很重要，但大多数关于细胞周期的研究 监管的重点是细胞的快速分裂。因此，目前尚不清楚细胞如何选择在 发育，以及为什么一些细胞可以选择离开G0，然后重新进入细胞周期 发育信号、组织损伤或营养可获得性，而其他人则不能。很明显， G0有多种状态，其中一些很容易逆转，另一些则是永久性的。不同 状态可以以不同的方式控制，既有细胞周期抑制的方式，也有 用于启动出口的路径。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以及如何调节G0的过程中，机械受到控制 在不同的情况下或多或少是可逆的。这项工作影响了广泛的生物学问题，如 适当地控制静止对发育和组织再生至关重要，但在衰老过程中会被破坏。 和癌症。

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.