Cell reprogramming has wide applications in tissue regeneration, disease modelling and personalized medicine. In addition to biochemical cues, mechanical forces also contribute to the modulation of the epigenetic state and a variety of cell functions through distinct mechanisms that are not fully understood. Here we show that millisecond deformation of the cell nucleus caused by confinement into microfluidic channels results in wrinkling and transient disassembly of the nuclear lamina, local detachment of lamina-associated domains in chromatin and a decrease of histone methylation (histone H3 lysine 9 trimethylation) and DNA methylation. These global changes in chromatin at the early stage of cell reprogramming boost the conversion of fibroblasts into neurons and can be partially reproduced by inhibition of histone H3 lysine 9 and DNA methylation. This mechanopriming approach also triggers macrophage reprogramming into neurons and fibroblast conversion into induced pluripotent stem cells, being thus a promising mechanically based epigenetic state modulation method for cell engineering.

细胞重编程在组织再生、疾病建模和个性化医疗中具有广泛的应用。除了生化信号外，机械力还通过尚未完全了解的不同机制有助于表观遗传状态和各种细胞功能的调节。在这里，我们表明，由于微流体通道的限制而引起的细胞核的毫秒变形会导致核纤层起皱和短暂分解、染色质中核纤层相关结构域的局部脱离以及组蛋白甲基化（组蛋白 H3 赖氨酸 9 三甲基化）的减少和DNA甲基化。细胞重编程早期阶段染色质的这些全局变化促进了成纤维细胞向神经元的转化，并且可以通过抑制组蛋白 H3 赖氨酸 9 和 DNA 甲基化来部分再现。这种机械启动方法还触发巨噬细胞重编程为神经元，以及成纤维细胞转化为诱导多能干细胞，因此是一种有前景的基于机械的表观遗传状态调节细胞工程方法。