Oligodendrocyte precursor differentiation is perturbed in the absence of the cyclin-dependent kinase inhibitor p27(Kip1)
Oligodendrocyte precursor differentiation is perturbed in the absence of the cyclin-dependent kinase inhibitor p27(Kip1)
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DOI：
10.1101/gad.11.18.2335
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发表时间：
1997-09-15
影响因子：
10.5
通讯作者：
Koff, A
中科院分区：
文献类型：
--
作者：
CasacciaBonnefil, P;Tikoo, R;Koff, A
在中枢神经系统的发育过程中，少突胶质细胞祖细胞（O-2A）经历有序的细胞增殖和分化模式，最终达到少突胶质细胞髓鞘化轴突的能力。在这里，我们报告，p27（Kip 1），细胞周期蛋白依赖性激酶抑制剂，是一个重要组成部分的决定O-2A细胞退出细胞周期。在体外，p27的积累与少突胶质细胞的分化相关。此外，与对照组相比，只有一部分来自p27敲除小鼠的O-2A细胞成功分化。不能分化与持续增殖相关，表明p27是O-2A细胞G（1）/G（0）转换所需机制的重要组成部分。在体内，O-2A前体的扩张在一定程度上导致了更大数量的少突胶质细胞。总之，这些数据表明，在决定退出少突胶质细胞谱系的细胞周期过程中，p27的作用。
During development of the central nervous system, oligodendrocyte progenitor cells (O-2A) undergo an orderly pattern of cell proliferation and differentiation, culminating in the ability of oligodendrocytes to myelinate axons. Here we report that p27(Kip1), a cyclin-dependent kinase inhibitor, is an important component of the decision of O-2A cells to withdraw from the cell cycle. In vitro, accumulation of p27 correlates with differentiation of oligodendrocytes. Furthermore, only a fraction of O-2A cells derived from p27-knockout mice differentiate successfully compared to controls. Inability to differentiate correlates with continued proliferation, suggesting that p27 is an important component of the machinery required for the G(1)/G(0) transition in O-2A cells. In vivo, expansion of O-2A precursors before withdrawal, in part, leads to a greater number of oligodendrocytes. Together these data indicate a role for p27 during the decision to withdraw from the cell cycle in the oligodendrocyte lineage.