Kim Mee-Hae, Thanuthanakhun Naruchit, Fujimoto Shun, Kino-Oka Masahiro
Department of Biotechnology, Graduate School of Engineering, Osaka University, 2-1 Yamadaoka, Suita, Osaka 565-0871, Japan.
Department of Biotechnology, Graduate School of Engineering, Osaka University, 2-1 Yamadaoka, Suita, Osaka 565-0871, Japan.
Stem Cell Res. 2021 Oct;56:102534. doi: 10.1016/j.scr.2021.102534. Epub 2021 Sep 7.
Understanding the cellular behavioral mechanisms underlying memory formation and maintenance in human induced pluripotent stem cell (hiPSC) culture provides key strategies for achieving stability and robustness of cell differentiation. Here, we show that changes in cell behavior-driven epigenetic memory of hiPSC cultures alter their pluripotent state and subsequent differentiation. Interestingly, pluripotency-associated genes were activated during the entire cell growth phases along with increased active modifications and decreased repressive modifications. This memory effect can last several days in the long-term stationary phase and was sustained in the aspect of cell behavioral changes after subculture. Further, changes in growth-related cell behavior were found to induce nucleoskeletal reorganization and active versus repressive modifications, thereby enabling hiPSCs to change their differentiation potential. Overall, we discuss the cell behavior-driven epigenetic memory induced by the culture environment, and the effect of previous memory on cell lineage specification in the process of hiPSC differentiation.
了解人类诱导多能干细胞（hiPSC）培养中记忆形成和维持的细胞行为机制，为实现细胞分化的稳定性和稳健性提供了关键策略。在此，我们表明，hiPSC培养中由细胞行为驱动的表观遗传记忆变化会改变其多能状态及后续分化。有趣的是，多能性相关基因在整个细胞生长阶段均被激活，同时活性修饰增加而抑制性修饰减少。这种记忆效应在长期静止期可持续数天，并在传代培养后的细胞行为变化方面得以维持。此外，发现与生长相关的细胞行为变化会诱导核骨架重组以及活性与抑制性修饰，从而使hiPSC能够改变其分化潜能。总体而言，我们讨论了由培养环境诱导的细胞行为驱动的表观遗传记忆，以及先前记忆对hiPSC分化过程中细胞谱系特化的影响。
