Heart extracellular matrix supports cardiomyocyte differentiation of mouse embryonic stem cells

Sayaka Higuchi, Qingsong Lin, Jigang Wang, Teck Kwang Lim, Shashikant B. Joshi, Ganesh Srinivasan Anand, Maxey C.M. Chung, Michael P. Sheetz, Hideaki Fujita

Research output: Contribution to journalArticlepeer-review

35 Scopus citations


We have evaluated the effect of heart extracellular matrix (ECM) on the cardiomyocyte differentiation of mouse embryonic stem cells (ES cells) using de-cellularized heart tissue. Several lines of evidence indicate that ECM plays significant roles in cell proliferation, cell death and differentiation, but role of ECM possessing a 3D structure in differentiation has not been studied in detail. We found that there are substantial differences in the quantitative protein profiles of ECM in SDS-treated heart tissue compared to that of liver tissue, as assessed by iTRAQ™ quantitative proteomics analysis. When mouse ES cells were cultured on thin (60 μm) sections of de-cellularized tissue, the expression of cardiac myosin heavy chain (cMHC) and cardiac troponin I (cTnI) was high in ES cells cultured on heart ECM compared with those cultured on liver ECM. In addition, the protein expression of cMHC and cTnI was detected in cells on heart ECM after 2 weeks, which was not detectable in cells on liver ECM. These results indicate that heart ECM plays a critical role in the cardiomyocyte differentiation of ES cells. We propose that tissue-specific ECM induced cell lineage specification through mechano-transduction mediated by the structure, elasticity and components of ECM.

Original languageEnglish (US)
Pages (from-to)320-325
Number of pages6
JournalJournal of Bioscience and Bioengineering
Issue number3
StatePublished - Mar 2013
Externally publishedYes


  • Cardiomyocyte
  • Differentiation
  • Embryonic stem cells
  • Extracellular matrix
  • Mechanobiology

ASJC Scopus subject areas

  • Biotechnology
  • Bioengineering
  • Applied Microbiology and Biotechnology


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