Open AccessLack of Laminin γ1 in Embryonic Stem Cell‐Derived Cardiomyocytes Causes Inhomogeneous Electrical Spreading Despite Intact Differentiation and Function
Author(s) -
Malan Daniela,
Reppel Michael,
Dobrowolski Radoslaw,
Roell Wilhelm,
Smyth Neil,
Hescheler Juergen,
Paulsson Mats,
Bloch Wilhelm,
Fleischmann Bernd K.
Publication year - 2009
Publication title -
stem cells
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.159
H-Index - 229
eISSN - 1549-4918
pISSN - 1066-5099
DOI - 10.1634/stemcells.2008-0335
Subject(s) - laminin , biology , microbiology and biotechnology , extracellular matrix , basement membrane , embryonic stem cell , myocyte , cellular differentiation , stem cell , morphogenesis , gene , genetics
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. S TEM C ELLS 2009;27:88–99