期刊
JOURNAL OF CELLULAR PHYSIOLOGY
卷 236, 期 7, 页码 4985-4996出版社
WILEY
DOI: 10.1002/jcp.30211
关键词
epigenetic modifications; human induced pluripotent stem cells; pluripotency; Rho– Rho kinase‐ phospho‐ myosin pathway; three‐ dimensional culture
资金
- Project Focused on Developing Key Evaluation Technology: Development of Platform Technology for Drug Discovery through Application of Regenerative Medicine from AMED [JP19be0604001]
This study investigated the epigenetic modifications and signaling pathways involved in maintaining pluripotency of hiPSCs under 3D culture conditions, showing alterations in the Rho-Rho kinase-phospho-myosin pathway and expression of pluripotency-associated factors. These findings suggest the potential for designing culture environments that support stable and high-quality hiPSCs.
Three-dimensional (3D) culture platforms have been explored to establish physiologically relevant cell culture environment and permit expansion scalability; however, little is known about the mechanisms underlying the regulation of pluripotency of human induced pluripotent stem cells (hiPSCs). This study elucidated epigenetic modifications contributing to pluripotency of hiPSCs in response to 3D culture. Unlike two-dimensional (2D) monolayer cultures, 3D cultured cells aggregated with each other to form ball-like aggregates. 2D cultured cells expressed elevated levels of Rac1 and RhoA; however, Rac1 level was significantly lower while RhoA level was persisted in 3D aggregates. Compared with 2D monolayers, the 3D aggregates also exhibited significantly lower myosin phosphorylation. Histone methylation analysis revealed remarkable H3K4me3 upregulation and H3K27me3 maintenance throughout the duration of 3D culture; in addition, we observed the existence of naive pluripotency signatures in cells grown in 3D culture. These results demonstrated that hiPSCs adapted to 3D culture through alteration of the Rho-Rho kinase-phospho-myosin pathway, influencing the epigenetic modifications and transcriptional expression of pluripotency-associated factors. These results may help design culture environments for stable and high-quality hiPSCs.
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