Lack of laminin γ1 in embryonic stem cell-derived cardiomyocytes causes inhomogeneous electrical spreading despite intact differentiation and function

Daniela Malan, Michael Reppel, Radoslaw Dobrowolski, Wilhelm Roell, Neil Smyth, Juergen Hescheler, Mats Paulsson, Wilhelm Bloch, Bernd K. Fleischmann

Research output: Contribution to journalArticlepeer-review

22 Scopus citations

Abstract

Laminins form a large family of extracellular matrix (ECM) proteins, and their expression is a prerequisite for normal embryonic development. Herein we investigated the role of the laminin γ1 chain for cardiac muscle differentiation and function using cardiomyocytes derived from embryonic stem cells deficient in the LAMC1 gene. Laminin γ1 (-/-) cardiomyocytes lacked basement membranes (BM), whereas their sarcomeric organization was unaffected. Accordingly, electrical activity and hormonal regulation were found to be intact. However, the inadequate BM formation led to an increase of ECM deposits between adjacent cardiomyocytes, and this resulted in defects of the electrical signal propagation. Furthermore, we also found an increase in the number of pacemaker areas. Thus, although laminin and intact BM are not essential for cardiomyocyte development and differentiation per se, they are required for the normal deposition of matrix molecules and critical for intact electrical signal propagation.

Original languageEnglish (US)
Pages (from-to)88-99
Number of pages12
JournalStem Cells
Volume27
Issue number1
DOIs
StatePublished - Jan 2009

Keywords

  • Embryonic stem-derived cardiomyocytes
  • Extracellular matrix
  • Hormonal regulation
  • Laminin γ1

ASJC Scopus subject areas

  • Molecular Medicine
  • Developmental Biology
  • Cell Biology

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