Cyclic mechanical strain maintains Nanog expression through PI3K/Akt signaling in mouse embryonic stem cells

Rie Horiuchi, Takayuki Akimoto, Zhang Hong, Takashi Ushida

Research output: Contribution to journalArticle

15 Citations (Scopus)

Abstract

Mechanical strain has been reported to affect the proliferation/differentiation of many cell types; however, the effects of mechanotransduction on self-renewal as well as pluripotency of embryonic stem (ES) cells remains unknown. To investigate the effects of mechanical strain on mouse ES cell fate, we examined the expression of Nanog, which is an essential regulator of self-renewal and pluripotency as well as Nanog-associated intracellular signaling during uniaxial cyclic mechanical strain. The mouse ES cell line, CCE was plated onto elastic membranes, and we applied 10% strain at 0.17. Hz. The expression of Nanog was reduced during ES cell differentiation in response to the withdrawal of leukemia inhibitory factor (LIF); however, two days of cyclic mechanical strain attenuated this reduction of Nanog expression. On the other hand, the cyclic mechanical strain promoted PI3K-Akt signaling, which is reported as an upstream of Nanog transcription. The cyclic mechanical strain-induced Akt phosphorylation was blunted by the PI3K inhibitor wortmannin. Furthermore, cytochalasin D, an inhibitor of actin polymerization, also inhibited the mechanical strain-induced increase in phospho-Akt. These findings imply that mechanical force plays a role in regulating Nanog expression in ES cells through the actin cytoskeleton-PI3K-Akt signaling.

Original languageEnglish
Pages (from-to)1726-1732
Number of pages7
JournalExperimental Cell Research
Volume318
Issue number14
DOIs
Publication statusPublished - 2012 Aug 15

Fingerprint

Embryonic Stem Cells
Phosphatidylinositol 3-Kinases
Cell Differentiation
Leukemia Inhibitory Factor
Cytochalasin D
Actin Cytoskeleton
Polymerization
Actins
Phosphorylation
Cell Line
Membranes
Mouse Embryonic Stem Cells

Keywords

  • Actin
  • Embryonic germ (EG)
  • Embryonic stem (ES)
  • Focal adhesion kinase (FAK)
  • Mechano-transduction
  • Mechanobiology
  • Stemness
  • Stretch

ASJC Scopus subject areas

  • Cell Biology

Cite this

Cyclic mechanical strain maintains Nanog expression through PI3K/Akt signaling in mouse embryonic stem cells. / Horiuchi, Rie; Akimoto, Takayuki; Hong, Zhang; Ushida, Takashi.

In: Experimental Cell Research, Vol. 318, No. 14, 15.08.2012, p. 1726-1732.

Research output: Contribution to journalArticle

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abstract = "Mechanical strain has been reported to affect the proliferation/differentiation of many cell types; however, the effects of mechanotransduction on self-renewal as well as pluripotency of embryonic stem (ES) cells remains unknown. To investigate the effects of mechanical strain on mouse ES cell fate, we examined the expression of Nanog, which is an essential regulator of self-renewal and pluripotency as well as Nanog-associated intracellular signaling during uniaxial cyclic mechanical strain. The mouse ES cell line, CCE was plated onto elastic membranes, and we applied 10{\%} strain at 0.17. Hz. The expression of Nanog was reduced during ES cell differentiation in response to the withdrawal of leukemia inhibitory factor (LIF); however, two days of cyclic mechanical strain attenuated this reduction of Nanog expression. On the other hand, the cyclic mechanical strain promoted PI3K-Akt signaling, which is reported as an upstream of Nanog transcription. The cyclic mechanical strain-induced Akt phosphorylation was blunted by the PI3K inhibitor wortmannin. Furthermore, cytochalasin D, an inhibitor of actin polymerization, also inhibited the mechanical strain-induced increase in phospho-Akt. These findings imply that mechanical force plays a role in regulating Nanog expression in ES cells through the actin cytoskeleton-PI3K-Akt signaling.",
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