Department of Physics, University of Cambridge, Cambridge, CB3 0HE, UK.
Integr Biol (Camb). 2011 Aug;3(8):863-7. doi: 10.1039/c1ib00003a. Epub 2011 Jun 22.
We hypothesised that global structural changes in stem cells would manifest with differentiation, and that these changes would be observable with light scattering microscopy. Analysed with a fractal dimension formalism, we observed significant structural changes in differentiating human mesenchymal stem cells within one day after induction, earlier than could be detected by gene expression profiling. Moreover, light scattering microscopy is entirely non-perturbative, so the same sample could be monitored throughout the differentiation process. We explored one possible mechanism, chromatin remodelling, to account for the changes we observed. Correlating with the staining of HP1α, a heterochromatin protein, we applied novel microscopy methods and fractal analysis to monitor the plastic dynamics of chromatin within stem cell nuclei. We showed that the level of chromatin condensation changed during differentiation, and provide one possible explanation for the changes seen with the light scattering method. These results lend physical insight into stem cell differentiation while providing physics-based methods for non-invasive detection of the differentiation process.
我们假设干细胞的全局结构变化会随着分化而表现出来，并且这些变化可以用光散射显微镜观察到。通过分形维数形式主义进行分析，我们在诱导后一天内观察到人类间充质干细胞的显著结构变化，比基因表达谱分析更早。此外，光散射显微镜完全是非侵入性的，因此可以在整个分化过程中监测同一样本。我们探索了一个可能的机制，即染色质重塑，以解释我们观察到的变化。我们应用了新的显微镜方法和分形分析来监测干细胞核内染色质的可塑性动力学，与异染色质蛋白 HP1α 的染色相关。我们表明，在分化过程中染色质的凝聚水平发生了变化，并为光散射方法观察到的变化提供了一种可能的解释。这些结果为干细胞分化提供了物理洞察力，同时为分化过程的非侵入性检测提供了基于物理的方法。
