在PU.1和细胞循环之间的正反控制了髓状细胞分化
Hao Yuan Kueh1, Ameya Champhekar, Ameya Champhekhar
1Division of Biology, California Institute of Technology, Pasadena, CA, USA. kueh@caltech.edu
Science (New York, N.Y.)
|July 23, 2013
概括
细胞周期持续时间通过积极的反稳定干细胞分化. 由于细胞周期较长,转录因子PU.1在巨细胞中的积累控制了细胞命运.
科学领域:
- 细胞和分子生物学 细胞和分子生物学
- 发展生物学 发展生物学
- 免疫学 免疫学 免疫学
背景情况:
- 积极反循环对于干细胞分化至关重要.
- 多种机制可以在基因调节电路中产生积极的反.
- 转录因子PU.1在淋巴细胞和骨髓细胞系的结合中起着关键作用.
研究的目的:
- 研究转录因子PU.1调节B细胞和巨细胞分化的特定反机制.
- 阐明细胞循环动态在PU.1-介导的细胞命运决定中的作用.
- 了解正的自我调节如何促进稳定的细胞分化.
主要方法:
- 定量活细胞成像监测PU.1水平和分化细胞中的细胞周期进展.
- 在原生细胞中对外源PU.1表达的实验操纵.
- 数学建模分析反架构及其对细胞周期持续时间和分化稳定性的影响.
主要成果:
- 发育中的B细胞通过减少转录来降低PU.1的调节.
- 发育中的巨细胞通过延长细胞周期持续时间来积累PU.1 ,从而形成稳定,缓慢分裂的状态.
- 外源PU.1表达诱导细胞周期延长,证明PU.1和细胞周期持续时间之间的正反.
- 数学模型证实,细胞循环合的反稳定了差异化的细胞状态.
结论:
- 细胞周期持续时间是控制PU.1水平的积极自我调节电路的组成部分.
- 这种细胞循环合的反机制有效地稳定了分化的细胞命运,特别是巨细胞.
- 转录因子水平和细胞周期动力学之间的相互作用为干细胞分化中的细胞命运决定提供了强大的策略.
相关概念视频
01:15Differentiation of Common Myeloid Progenitor Cells
Common myeloid progenitors (CMPs) are oligopotent cells that can differentiate into granulocytes and macrophages. Granulocytes and macrophages are essential for protecting the body against bacterial, viral, or fungal infections. They migrate from the bone marrow into the circulating blood to reach specific tissue sites where they differentiate and help in immune surveillance. However, they survive only for a few days and must be continuously made available to the organism to maintain a robust...
02:23Abnormal Proliferation
Under normal conditions, most adult cells remain in a non-proliferative state unless stimulated by internal or external factors to replace lost cells. Abnormal cell proliferation is a condition in which the cell's growth exceeds and is uncoordinated with normal cells. In such situations, cell division persists in the same excessive manner even after cessation of the stimuli, leading to persistent tumors. The tumor arises from the damaged cells that replicate to pass the damage to the daughter...
01:21Lineage Commitment
Commitment is the process whereby stem cells:
02:38Mitogens and the Cell Cycle
Mitogens and their receptors play a crucial role in controlling the progression of the cell cycle. However, the loss of mitogenic control over cell division leads to tumor formation. Therefore, mitogens and mitogen receptors play an important role in cancer research. For instance, the epidermal growth factor (EGF) - a type of mitogen and its transmembrane receptor (EGFR), decides the fate of the cell's proliferation. When EGF binds to EGFR, a member of the ErbB family of tyrosine kinase...
02:36Cells Coordinate Growth and Proliferation
Cell size is a significant factor impacting cellular design, function, and fitness. There exists some internal coordination by which cells double their masses before division, thus, achieving homeostasis. Coordination between cell growth and proliferation depends on the checkpoints in between cell cycle phases. Loss of coordination or failure in the checkpoint mechanism can drive the cell to uncontrolled growth and loss of cellular function. Like dividing cells that coordinate cellular growth,...
01:23Negative Regulator Molecules
Positive regulators allow a cell to advance through cell cycle checkpoints. Negative regulators have an equally important role as they terminate a cell’s progression through the cell cycle—or pause it—until the cell meets specific criteria.