標題: The effects of actin cytoskeleton perturbation on keratin intermediate filament formation in mesenChymal stem/stromal cells
作者: Chang, Tzu-Hao
Huang, Hsien-Da
Ong, Wei-Kee
Fu, Yun-Ju
Lee, Oscar K.
Chien, Shu
Ho, Jennifer H.
生物科技學系
生物資訊及系統生物研究所
Department of Biological Science and Technology
Institude of Bioinformatics and Systems Biology
關鍵字: Chromosome 17q21.2;F-actin depolymerization;Intermediate filaments;Keratin;Mesenchymal stem cells (MSCs);NK2 homeobox 5 (NK2.5)
公開日期: 1-四月-2014
摘要: F-actin plays a crucial role in composing the three-dimensional cytoskeleton and F-actin depolymerization alters fate choice of mesenchymal stem/stromal cells (MSCs). Here, we investigated differential gene expression and subsequent physiological changes in response to F-actin perturbation by latrunculin B in MSCs. Nineteen genes were down-regulated and 27 genes were up-regulated in the first 15 min after F-actin depolymerization. Functional enrichment analysis revealed that five genes involved in keratin (KRT) intermediate filaments clustering in the chromosome 17q21.2 region, i.e., KRT14, KRT19, KRT34, KRT-associated protein (KRTAP) 1-5, and KRTAP2-3, were strongly up-regulated. Transcription factor prediction identified NKX2.5 as the potential transcription factor to control KRT19, KRT34, KRTAP1-5, and KRTAP2-3; and indeed, the protein level of NKX2.5 was markedly increased in the nuclear fraction within 15 min of F-actin depolymerization. The peak of keratin intermediate filament formation was 1 h after actin perturbation, and the morphological changes showed by decrease in the ratio of long-axis to shortaxis diameter in MSCs was observed after 4 h. Together, F-actin depolymerization rapidly triggers keratin intermediate filament formation by turning on keratin-related genes on chromosome 17q21.2. Such findings offer new insight in lineage commitment of MSCs and further scaffold design in MSC-based tissue engineering. (C) 2014 Elsevier Ltd. All rights reserved.
URI: http://dx.doi.org/10.1016/j.biomaterials.2014.01.028
http://hdl.handle.net/11536/24253
ISSN: 0142-9612
DOI: 10.1016/j.biomaterials.2014.01.028
期刊: BIOMATERIALS
Volume: 35
Issue: 13
起始頁: 3934
結束頁: 3944
顯示於類別:期刊論文


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  1. 000334481000003.pdf