Telomere shortening and chromosomal instability abrogates proliferation of adult but not embryonic neural stem cells
Telomere shortening and chromosomal instability abrogates proliferation of adult but not embryonic neural stem cells
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DOI：
10.1242/dev.01215
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发表时间：
2004-08-01
期刊：
影响因子：
4.6
通讯作者：
Blasco, MA
中科院分区：
文献类型：
--
作者：
Ferrón, S;Mira, H;Blasco, MA
染色体完整性对于细胞活力是必不可少的，因此，高度增殖的细胞类型需要活性端粒延伸机制来无限生长。一致地，在基因修饰的小鼠品系中端粒酶活性的缺失导致到目前为止分析的所有高度增殖的细胞群体中的生长障碍。我们发现，端粒磨损显着损害成年神经干细胞（NSCs）的体外增殖分离从脑室下区（SVZ）的端粒酶缺陷的成年小鼠。在没有外源性促有丝分裂刺激的情况下，在体内也观察到出生后神经源性祖细胞的增殖减少。引人注目的是，严重的端粒侵蚀导致染色体异常和核积累的p53并没有影响胚胎神经干细胞的体外增殖潜力。这些结果表明，胚胎和成人神经祖细胞之间存在内在差异，在他们的端粒缩短的反应，和一些群体的组织特异性干细胞可以绕过DNA损伤检查点。
Chromosome integrity is essential for cell viability and, therefore, highly proliferative cell types require active telomere elongation mechanisms to grow indefinitely. Consistently, deletion of telomerase activity in a genetically modified mouse strain results in growth impairments in all highly proliferative cell populations analyzed so far. We show that telomere attrition dramatically impairs the in vitro proliferation of adult neural stem cells (NSCs) isolated from the subventricular zone (SVZ) of telomerase-deficient adult mice. Reduced proliferation of postnatal neurogenic progenitors was also observed in vivo, in the absence of exogenous mitogenic stimulation. Strikingly, severe telomere erosion resulting in chromosomal abnormalities and nuclear accumulation of p53 did not affect the in vitro proliferative potential of embryonic NSCs. These results suggest that intrinsic differences exist between embryonic and adult neural progenitor cells in their response to telomere shortening, and that some populations of tissue-specific stem cells can bypass DNA damage check points.