期刊
BIOMATERIALS
卷 35, 期 8, 页码 2411-2419出版社
ELSEVIER SCI LTD
DOI: 10.1016/j.biomaterials.2013.12.010
关键词
Stem cells; Micro-patterns; Nuclear mechanics; Transcription factor compartmentalization; Global gene expression
资金
- Mechanobiology Institute (MBI) and Department of Biological Sciences (DBS), National University of Singapore (NUS), Singapore
Embryonic stem (ES) cells exhibit plasticity in nuclear organization as well as variability in gene expression. Although such physicochemical features are important in lineage commitment, mechanistic insights coupling nuclear plasticity and gene expression have not been elucidated. To probe this, we developed single cell micro-patterned assay to map nuclear deformation and its correlation with gene expression. We found an inherent heterogeneity in nuclear pliability of ES cells. Softer nuclei deformed to the underlying substrate geometry while the stiffer ones remained spherical. Stiffer nuclei were strongly correlated with decreased global histone (H3) acetylation and an increase in Lamin A/C expression. Interestingly, these cells also have higher nuclear accumulation of the transcription cofactor MRTF-A (myocardin-related transcription factor A) and an upregulation of its downstream target genes. Taken together, our results provide compelling evidence to show that the mechanical heterogeneity of stem cell nucleus can regulate transcriptional programs during onset of cellular differentiation. (C) 2013 Elsevier Ltd. All rights reserved.
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