Architectural control of mesenchymal stem cell phenotype through nuclear actin.

Architectural control of mesenchymal stem cell phenotype through nuclear actin.
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DOI:
10.1080/19491034.2022.2029297
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发表时间:
2022-12
期刊:
Nucleus (Austin, Tex.)
影响因子:
--
通讯作者:
Uzer G
Uzer G
中科院分区:
其他
文献类型:
--
作者:
Rubin J;van Wijnen AJ;Uzer G

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越来越多的人认识到,细胞核的结构成分通过改变染色质组织来调节基因的可及性。虽然核膜连接蛋白将机械敏感的肌动蛋白细胞骨架与核骨架连接起来,但肌动蛋白对细胞核内部结构的贡献仍然是一个谜。肌动蛋白转运进入细胞核的控制,加上细胞核内控制肌动蛋白结构的蛋白质(肌动蛋白工具箱)的存在,表明核肌动蛋白可能支持基因表达的生物力学调节。细胞肌动蛋白结构是机械反应性的:肌动蛋白索通过在质膜上所受的力而产生,并将力传递到细胞核。我们假设动态肌动蛋白重塑对这些生物力学线索的响应提供了对表观遗传景观的新水平的结构控制。在此,我们建议人们认识到机械力可以促进肌动蛋白转移到细胞核中,并控制间充质干细胞的结构安排,从而调节谱系承诺。
There is growing appreciation that architectural components of the nucleus regulate gene accessibility by altering chromatin organization. While nuclear membrane connector proteins link the mechanosensitive actin cytoskeleton to the nucleoskeleton, actin’s contribution to the inner architecture of the nucleus remains enigmatic. Control of actin transport into the nucleus, plus the presence of proteins that control actin structure (the actin tool-box) within the nucleus, suggests that nuclear actin may support biomechanical regulation of gene expression. Cellular actin structure is mechanoresponsive: actin cables generated through forces experienced at the plasma membrane transmit force into the nucleus. We posit that dynamic actin remodeling in response to such biomechanical cues provides a novel level of structural control over the epigenetic landscape. We here propose to bring awareness to the fact that mechanical forces can promote actin transfer into the nucleus and control structural arrangements as illustrated in mesenchymal stem cells, thereby modulating lineage commitment.
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