Physical plasticity of the nucleus in stem cell differentiation
Physical plasticity of the nucleus in stem cell differentiation
复制标题
DOI：
10.1073/pnas.0702576104
复制
发表时间：
2007-10-02
影响因子：
11.1
通讯作者：
Discher, Dennis E.
中科院分区：
文献类型：
--
作者：
Pajerowski, J. David;Dahl, Kris Noel;Discher, Dennis E.
胚胎发生中的细胞分化涉及细胞核内基因表达结构重组的广泛变化，包括染色质浓缩和核蛋白固定。因此，我们假设幼稚干细胞的细胞核具有物理可塑性，并且比分化细胞的细胞核更柔韧。显微操作方法确实表明，人类胚胎干细胞的细胞核是高度可变形的，通过终末分化可变形106倍，而人类成体干细胞的细胞核具有中等硬度，并且不可逆地变形。由于核骨架组分核纤层蛋白A/C在两种类型的干细胞中都不表达，我们敲低了人上皮细胞中的核纤层蛋白A/C，并测量了与成人造血干细胞相似的变形性。在流变学上，层蛋白缺乏的状态被证明是最像流体的，特别是在变形的第一个近似10秒内。持续时间超过这个时间的核扭曲是不可逆的，荧光成像的光漂白微变形证实，染色质确实流动，膨胀，重组，而板拉伸。因此，核的流变特性主要由核质/染色质决定，而变形的程度则由纤层调节。
Cell differentiation in embryogenesis involves extensive changes in gene expression structural reorganization within the nucleus, including chromatin condensation and nucleoprotein immobilization. We hypothesized that nuclei in naive stem cells would therefore prove to be physically plastic and also more pliable than nuclei in differentiated cells. Micromanipulation methods indeed show that nuclei in human embryonic stem cells are highly deformable and stiffen 6-fold through terminal differentiation, and that nuclei in human adult stem cells possess an intermediate stiffness and deform irreversibly. Because the nucleo-skeletal component Lamin A/C is not expressed in either type of stem cell, we knocked down Lamin A/C in human epithelia] cells and measured a deformability similar to that of adult hematopoietic stem cells. Rheologically, lamin-deficient states prove to be the most fluid-like, especially within the first approximate to 10 sec of deformation. Nuclear distortions that persist longer than this are irreversible, and fluorescence-imaged microdeformation with photobleaching confirms that chromatin indeed flows, distends, and reorganizes while the lamina stretches. The rheological character of the nucleus is thus set largely by nucleoplasm/chromatin, whereas the extent of deformation is modulated by the lamina.