Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales (IQUIBICEN), CONICET-Universidad de Buenos Aires, Facultad de Ciencias Exactas y Naturales, C1428EGA, Buenos Aires, Argentina.
Departamento de Fisiología, Biología Molecular y Celular, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, C1428EGA, Buenos Aires, Argentina.
BMC Biol. 2022 Jan 7;20(1):6. doi: 10.1186/s12915-021-01207-w.
The cytoskeleton is a key component of the system responsible for transmitting mechanical cues from the cellular environment to the nucleus, where they trigger downstream responses. This communication is particularly relevant in embryonic stem (ES) cells since forces can regulate cell fate and guide developmental processes. However, little is known regarding cytoskeleton organization in ES cells, and thus, relevant aspects of nuclear-cytoskeletal interactions remain elusive.
We explored the three-dimensional distribution of the cytoskeleton in live ES cells and show that these filaments affect the shape of the nucleus. Next, we evaluated if cytoskeletal components indirectly modulate the binding of the pluripotency transcription factor OCT4 to chromatin targets. We show that actin depolymerization triggers OCT4 binding to chromatin sites whereas vimentin disruption produces the opposite effect. In contrast to actin, vimentin contributes to the preservation of OCT4-chromatin interactions and, consequently, may have a pro-stemness role.
Our results suggest roles of components of the cytoskeleton in shaping the nucleus of ES cells, influencing the interactions of the transcription factor OCT4 with the chromatin and potentially affecting pluripotency and cell fate.
细胞骨架是负责将细胞外环境的机械线索传递到细胞核的系统的关键组成部分,在细胞核中,它们引发下游反应。这种通讯在胚胎干细胞 (ES) 中尤为重要,因为力可以调节细胞命运并指导发育过程。然而,关于 ES 细胞中细胞骨架的组织知之甚少,因此,核-细胞骨架相互作用的相关方面仍然难以捉摸。
我们探索了活 ES 细胞中细胞骨架的三维分布,表明这些纤维会影响细胞核的形状。接下来,我们评估了细胞骨架成分是否间接调节多潜能转录因子 OCT4 与染色质靶标的结合。我们表明,肌动蛋白解聚会触发 OCT4 与染色质位点的结合,而中间丝的破坏则会产生相反的效果。与肌动蛋白相反,中间丝有助于 OCT4-染色质相互作用的维持,因此可能具有促进干性的作用。
我们的结果表明细胞骨架成分在塑造 ES 细胞的细胞核、影响转录因子 OCT4 与染色质的相互作用以及潜在影响多能性和细胞命运方面发挥作用。