Department of Biological Sciences, Centre for Bioimaging Sciences, National University of Singapore, Singapore 117557, Singapore.
Department of Biological Sciences, Centre for Bioimaging Sciences, National University of Singapore, Singapore 117557, Singapore; Mechanobiology Institute, National University of Singapore, Singapore 117411, Singapore.
Cell Rep. 2017 Jul 11;20(2):397-410. doi: 10.1016/j.celrep.2017.06.057.
Cell size homeostasis can be achieved by size checkpoints that couple cell size to cell-cycle progression or by alternative mechanisms such as constant extension. In mammalian cells, the existence of strict size checkpoints remains controversial due to the technical limitations in determining cell size directly and accurately. We developed a microfabricated channel system that linearizes mammalian cell growth and facilitates cell size measurements. By tracking cell length, while directly visualizing cell-cycle progression in rat basophilic leukemia cells and RAW 264.7 macrophages, we examined the mechanisms of size homeostasis and the existence of a size checkpoint at the G1/S transition. Our analysis revealed a two-tier size homeostasis mechanism where a G1 "sizer" or "adder" could operate, depending on the birth size of the cells.
细胞大小的内稳态可以通过大小检测点来实现,这些检测点将细胞大小与细胞周期进程相耦合,或者通过诸如恒定延伸等替代机制来实现。在哺乳动物细胞中,由于直接准确地确定细胞大小的技术限制,严格的大小检测点的存在仍然存在争议。我们开发了一种微加工通道系统,该系统使哺乳动物细胞的生长线性化,并便于进行细胞大小测量。通过跟踪细胞长度,同时直接观察大鼠嗜碱性白血病细胞和 RAW 264.7 巨噬细胞中的细胞周期进程,我们研究了大小内稳态的机制以及在 G1/S 转换时大小检测点的存在。我们的分析揭示了一种两级大小内稳态机制,其中 G1“定标器”或“加法器”可以根据细胞的出生大小来操作。