The effects of actin cytoskeleton perturbation on keratin intermediate filament formation in mesenchymal stem/stromal cells

Tzu Hao Chang, Hsien Da Huang, Wei Kee Ong, Yun Ju Fu, Oscar K. Lee, Shu Chien, Jennifer H. Ho

Research output: Contribution to journalArticle

16 Citations (Scopus)

Abstract

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 15min 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 15min of F-actin depolymerization. The peak of keratin intermediate filament formation was 1h after actin perturbation, and the morphological changes showed by decrease in the ratio of long-axis to short-axis diameter in MSCs was observed after 4h. 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.

Original languageEnglish
Pages (from-to)3934-3944
Number of pages11
JournalBiomaterials
Volume35
Issue number13
DOIs
Publication statusPublished - Apr 2014

Fingerprint

Keratin
Intermediate Filaments
Keratins
Stem cells
Mesenchymal Stromal Cells
Actin Cytoskeleton
Depolymerization
Actins
Genes
Transcription factors
Chromosomes
Proteins
Transcription Factors
Scaffolds (biology)
Tissue engineering
Gene expression
Tissue Engineering
Cytoskeleton
Cluster Analysis

Keywords

  • Chromosome 17q21.2
  • F-actin depolymerization
  • Intermediate filaments
  • Keratin
  • Mesenchymal stem cells (MSCs)
  • NK2 homeobox 5 (NKX2.5)

ASJC Scopus subject areas

  • Biomaterials
  • Bioengineering
  • Ceramics and Composites
  • Mechanics of Materials
  • Biophysics
  • Medicine(all)

Cite this

The effects of actin cytoskeleton perturbation on keratin intermediate filament formation in mesenchymal stem/stromal cells. / Chang, Tzu Hao; Huang, Hsien Da; Ong, Wei Kee; Fu, Yun Ju; Lee, Oscar K.; Chien, Shu; Ho, Jennifer H.

In: Biomaterials, Vol. 35, No. 13, 04.2014, p. 3934-3944.

Research output: Contribution to journalArticle

Chang, Tzu Hao ; Huang, Hsien Da ; Ong, Wei Kee ; Fu, Yun Ju ; Lee, Oscar K. ; Chien, Shu ; Ho, Jennifer H. / The effects of actin cytoskeleton perturbation on keratin intermediate filament formation in mesenchymal stem/stromal cells. In: Biomaterials. 2014 ; Vol. 35, No. 13. pp. 3934-3944.
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