Oligodendrocyte precursor cells count time but not cell divisions before differentiation
Oligodendrocyte precursor cells count time but not cell divisions before differentiation
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DOI：
10.1016/s0960-9822(06)00060-1
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发表时间：
1997-02-01
期刊：
影响因子：
9.2
通讯作者：
Raff, M
中科院分区：
文献类型：
--
作者：
Gao, FB;Durand, B;Raff, M
在脊椎动物的发育过程中，许多类型的前体细胞在停止并最终分化之前分裂有限的次数，目前尚不清楚是什么限制了细胞的增殖并导致细胞停止分裂。停止机制很重要，因为它们影响分化细胞的数量和分化的时间，我们一直在研究少突胶质细胞谱系中的“停止”问题[1,2]，它负责脊椎动物中枢神经系统的髓鞘形成，先前的研究表明，从发育中的大鼠视神经中分离的少突胶质前体细胞的增殖受到内在“时钟”机制的限制[3]。它由两部分组成：一是计算时间或细胞分裂的计数机制，二是当达到适当的时间时，阻滞细胞周期并启动细胞分化的效应机制[4,5]。在本研究中，我们解决了计数机制是否通过计数细胞分裂来运作的问题。我们发现，在33℃培养的前体细胞分裂更慢，但在细胞分裂更少后，停止分裂和分化更快，比在37℃培养的前体细胞分裂更慢，这表明计数机制不计算细胞分裂，而是以其他方式测量时间。我们发现周期蛋白依赖性激酶抑制剂p27(Kip1) （p27）的水平在33℃时比在37℃时上升得更快，这与先前的证据一致，即p27的积累可能是计数机制的一部分。
During vertebrate development, many types of precursor cell divide a limited number of times before they stop and terminally differentiate, It is unclear what limits cell proliferation and causes the cells to stop dividing when they do. The stopping mechanisms are important as they influence both the number of differentiated cells generated and the timing of differentiation, We have been studying the 'stopping' problem in the oligodendrocyte cell lineage [1,2], which is responsible for myelination in the vertebrate central nervous system, Previous studies demonstrated that the proliferation of oligodendrocyte precursor cells isolated from the developing rat optic nerve is limited by an intrinsic 'clock' mechanism [3], which consists of two components: a counting mechanism that counts time or cell divisions, and an effector mechanism that arrests the cell cycle and initiates cell differentiation when the appropriate time is reached [4,5]. In the present study, we address the question of whether the counting mechanism operates by counting cell divisions, We show that precursor cells cultured at 33 degrees C divide more slowly but stop dividing and differentiate sooner, after fewer cell divisions, than when they are cultured at 37 degrees C, indicating that the counting mechanism does not count cell divisions but measures time in some other way, In addition, we show that the levels of the cyclin-dependent kinase inhibitor p27(Kip1) (p27) rise faster at 33 degrees C than at 37 degrees C, consistent with previous evidence [6] that the accumulation of p27 may be part of the counting mechanism.