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3D culture increases pluripotent gene expression in mesenchymal stem cells through relaxation of cytoskeleton tension
Author(s) -
Zhou Ying,
Chen Haiyan,
Li Hong,
Wu Yaojiong
Publication year - 2017
Publication title -
journal of cellular and molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.44
H-Index - 130
eISSN - 1582-4934
pISSN - 1582-1838
DOI - 10.1111/jcmm.12946
Subject(s) - homeobox protein nanog , microbiology and biotechnology , mesenchymal stem cell , cytoskeleton , cytochalasin d , actin cytoskeleton , biology , rex1 , chemistry , cell , induced pluripotent stem cell , embryonic stem cell , genetics , gene
Three‐dimensional (3D) culture has been shown to improve pluripotent gene expression in mesenchymal stem cells ( MSC s), but the underlining mechanisms were poorly understood. Here, we found that the relaxation of cytoskeleton tension of MSC s in 3D culture was critically associated with the expressional up‐regulation of Nanog. Cultured in spheroids, MSC s showed decreased integrin‐based cell–matrix adhesion but increased cadherin‐based cell–cell interaction. Different from that in 2D culture, where MSC s exhibited branched and multiple‐directed F‐actin stress bundles at the cell edge and strengthened stress fibres transversing the cell body, MSC s 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 si RNA in 2D‐cultured MSC s 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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