A crucial role for p57Kip2 in the intracellular timer that controls oligodendrocyte differentiation
A crucial role for p57Kip2 in the intracellular timer that controls oligodendrocyte differentiation
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DOI：
10.1523/jneurosci.0628-07.2007
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发表时间：
2007-06-06
影响因子：
5.3
通讯作者：
Barres, Ben A.
中科院分区：
文献类型：
--
作者：
Dugas, Jason C.;Ibrahim, Adiljan;Barres, Ben A.
控制少突胶质细胞分化时间的细胞内分子机制仍然未知。Temple和Raff（1986）先前表明，少突胶质细胞前体细胞（OPC）在其子细胞同时停止增殖并分化成少突胶质细胞之前最多可分裂约8次。他们推测，随着时间的推移，细胞内分子的水平可能在每个子细胞中同步变化，最终达到阻止额外增殖的水平。在这里，我们报告发现这样的分子，细胞周期蛋白依赖性激酶抑制剂p57（Kip2）（Cdkn1c）。我们在体外实验中发现，一个OPCs克隆的所有子代都表达相似水平的p57（Kip2），在增殖的OPCs中，p57（Kip2）水平随时间推移而增加，并且p57（Kip2）水平调节OPC在分化前可以分裂多少次。这些发现揭示了OPCs测量时间的机制的一个新部分，并且可能扩展到许多其他前体细胞类型中的类似计时器。
The intracellular molecular mechanism that controls the timing of oligodendrocyte differentiation remains unknown. Temple and Raff (1986) previously showed that an oligodendrocyte precursor cell (OPC) can divide a maximum of approximately eight times before its daughter cells simultaneously cease proliferating and differentiate into oligodendrocytes. They postulated that over time the level of an intracellular molecule might synchronously change in each daughter cell, ultimately reaching a level that prohibited additional proliferation. Here, we report the discovery of such a molecule, the cyclin-dependent kinase inhibitor p57(Kip2) (Cdkn1c). We show in vitro that all daughters of a clone of OPCs express similar levels of p57(Kip2), that p57(Kip2) levels increase over time in proliferating OPCs, and that p57(Kip2) levels regulate how many times an OPC can divide before differentiating. These findings reveal a novel part of the mechanism by which OPCs measure time and are likely to extend to similar timers in many other precursor cell types.