期刊
JOURNAL OF CELLULAR AND MOLECULAR MEDICINE
卷 21, 期 6, 页码 1073-1084出版社
WILEY
DOI: 10.1111/jcmm.12946
关键词
mesenchymal stem cell; 3D; actin cytoskeleton; Nanog
资金
- Natural Science Foundation of China [31371404, 31571429]
- Natural Science Foundation of Guangdong [2015A030311041]
- Shenzhen Science and Technology Innovation Committee [JCYJ20140417115840279, GJHZ20150316160614842, JCYJ20160301150838144]
Three-dimensional (3D) culture has been shown to improve pluripotent gene expression in mesenchymal stem cells (MSCs), but the underlining mechanisms were poorly understood. Here, we found that the relaxation of cytoskeleton tension of MSCs in 3D culture was critically associated with the expressional up-regulation of Nanog. Cultured in spheroids, MSCs showed decreased integrin-based cell-matrix adhesion but increased cadherin-based cell-cell interaction. Different from that in 2D culture, where MSCs exhibited branched and multiple-directed F-actin stress bundles at the cell edge and strengthened stress fibres transversing the cell body, MSCs cultured in spheroids showed compact cell body, relaxed cytoskeleton tension with very thin cortical actin filament outlining the cell, and increased expression of Nanog along with reduced levels of Suv39h1 (H3K9 methyltransferase) and H3K9me3. Notably, pharmaceutical inhibition of actin polymerization with cytochalasin D or silencing Suv39h1 expression with siRNA in 2D-cultured MSCs elevated the expression of Nanog via H3K9 demethylation. Thus, our data suggest that 3D culture increases the expression of Nanog through the relaxation of actin cytoskeleton, which mediates reduced Suv39h1 and H3K9me3 levels.
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