Righolt Christiaan H, van 't Hoff Merel L R, Vermolen Bart J, Young Ian T, Raz Vered
Department of Human Genetics, Leiden University Medical Center, The Netherlands.
Aging (Albany NY). 2011 Dec;3(12):1192-201. doi: 10.18632/aging.100414.
Changes in the shape of the nuclear lamina are exhibited in senescent cells, as well as in cells expressing mutations in lamina genes. To identify cells with defects in the nuclear lamina we developed an imaging method that quantifies the intensity and curvature of the nuclear lamina. We show that this method accurately describes changes in the nuclear lamina. Spatial changes in nuclear lamina coincide with redistribution of lamin A proteins and local reduction in protein mobility in senescent cell. We suggest that local accumulation of lamin A in the nuclear envelope leads to bending of the structure. A quantitative distinction of the nuclear lamina shape in cell populations was found between fresh and senescent cells, and between primary myoblasts from young and old donors. Moreover, with this method mutations in lamina genes were significantly distinct from cells with wild-type genes. We suggest that this method can be applied to identify abnormal cells during aging, in in vitro propagation, and in lamina disorders.
核纤层形状的变化在衰老细胞以及表达核纤层基因突变的细胞中均有表现。为了识别核纤层存在缺陷的细胞，我们开发了一种成像方法，用于量化核纤层的强度和曲率。我们证明该方法能够准确描述核纤层的变化。核纤层的空间变化与衰老细胞中核纤层蛋白A的重新分布以及蛋白质流动性的局部降低相吻合。我们认为核纤层蛋白A在核膜中的局部积累会导致结构弯曲。在新鲜细胞与衰老细胞之间，以及来自年轻和年老供体的原代成肌细胞之间，发现了细胞群体中核纤层形状的定量差异。此外，通过该方法，核纤层基因突变细胞与野生型基因细胞存在显著差异。我们认为该方法可用于识别衰老过程中、体外增殖过程中以及核纤层疾病中的异常细胞。
