Chromatin reprogramming and bone regeneration in vitro and in vivo via the microtopography-induced constriction of cell nuclei-猫眼课题宝

DOI：

10.1038/s41551-023-01053-x

发表时间：

2023-06

期刊：

Nature Biomedical Engineering

影响因子：

28.1

通讯作者：

中科院分区：

工程技术1区

文献类型：

作者：

Xinlong Wang;Vasundhara Agrawal;Cody Dunton;Yugang Liu;R. Virk;Priyam Patel;Lucas Carter;Emily M. Pujadas;Yue Li;Surbhi Jain;Hao Wang;Na Ni;H. Tsai;N. Rivera‐Bolanos;J. Frederick;E. Roth;Reiner Bleher;C. Duan;P. Ntziachristos;Tongmei He;R. Reid;B. Jiang;H. Subramanian;V. Backman;G. Ameer

细胞上的地形线索可以通过接触引导改变细胞可塑性并加速培养组织的再生。在这里，我们展示了通过接触引导微柱模式诱导的人间充质基质细胞的核和细胞形态的变化如何影响细胞染色质的构象及其在体外和体内的成骨分化。微柱影响核结构，核纤层蛋白A/C多聚化和3D染色质构象，随后的转录重编程增强了细胞对成骨分化因子的反应性，并降低了它们的可塑性和脱靶分化。在具有临界尺寸颅骨缺损的小鼠中，具有诱导核收缩的微柱图案的植入物改变了细胞的染色质构象并增强了骨再生，而不需要外源性信号分子。我们的研究结果表明，医疗器械的拓扑结构可以通过染色质重编程来促进骨再生。

Topographical cues on cells can, through contact guidance, alter cellular plasticity and accelerate the regeneration of cultured tissue. Here we show how changes in the nuclear and cellular morphologies of human mesenchymal stromal cells induced by micropillar patterns via contact guidance influence the conformation of the cells’ chromatin and their osteogenic differentiation in vitro and in vivo. The micropillars impacted nuclear architecture, lamin A/C multimerization and 3D chromatin conformation, and the ensuing transcriptional reprogramming enhanced the cells’ responsiveness to osteogenic differentiation factors and decreased their plasticity and off-target differentiation. In mice with critical-size cranial defects, implants with micropillar patterns inducing nuclear constriction altered the cells’ chromatin conformation and enhanced bone regeneration without the need for exogenous signalling molecules. Our findings suggest that medical device topographies could be designed to facilitate bone regeneration via chromatin reprogramming.

Chromatin reprogramming and bone regeneration in vitro and in vivo via the microtopography-induced constriction of cell nuclei

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