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Tracking the mechanical dynamics of human embryonic stem cell chromatin

机译:追踪人类胚胎干细胞染色质的机械动力学

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Background A plastic chromatin structure has emerged as fundamental to the self-renewal and pluripotent capacity of embryonic stem (ES) cells. Direct measurement of chromatin dynamics in vivo is, however, challenging as high spatiotemporal resolution is required. Here, we present a new tracking-based method which can detect high frequency chromatin movement and quantify the mechanical dynamics of chromatin in live cells. Results We use this method to study how the mechanical properties of chromatin movement in human embryonic stem cells (hESCs) are modulated spatiotemporally during differentiation into cardiomyocytes (CM). Notably, we find that pluripotency is associated with a highly discrete, energy-dependent frequency of chromatin movement that we refer to as a ‘breathing’ state. We find that this ‘breathing’ state is strictly dependent on the metabolic state of the cell and is progressively silenced during differentiation. Conclusions We thus propose that the measured chromatin high frequency movements in hESCs may represent a hallmark of pluripotency and serve as a mechanism to maintain the genome in a transcriptionally accessible state. This is a result that could not have been observed without the high spatial and temporal resolution provided by this novel tracking method.
机译:背景技术塑性染色质结构已成为胚胎干(ES)细胞自我更新和多能能力的基础。然而,由于需要高的时空分辨率,因此直接测量体内染色质动力学是一项挑战。在这里,我们提出了一种基于跟踪的新方法,该方法可以检测高频染色质运动并量化活细胞中染色质的机械动力学。结果我们使用这种方法来研究人类胚胎干细胞(hESCs)中染色质运动的机械特性如何在分化为心肌细胞(CM)的过程中进行时空调节。值得注意的是,我们发现多能性与染色质运动的高度离散的,与能量有关的频率相关,我们称之为“呼吸”状态。我们发现这种“呼吸”状态严格取决于细胞的代谢状态,并且在分化过程中逐渐沉默。结论因此,我们建议在hESCs中测得的染色质高频移动可能代表了多能性的标志,并作为将基因组维持在转录可访问状态的一种机制。如果没有这种新颖的跟踪方法提供的高时空分辨率,就无法观察到这一结果。

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