Lack of Laminin γ1 in Embryonic Stem Cell-Derived Cardiomyocytes Causes Inhomogeneous Electrical Spreading Despite Intact Differentiation and Function
Lack of Laminin γ1 in Embryonic Stem Cell-Derived Cardiomyocytes Causes Inhomogeneous Electrical Spreading Despite Intact Differentiation and Function
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DOI：
10.1634/stemcells.2008-0335
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发表时间：
2009-01-01
期刊：
影响因子：
5.2
通讯作者：
Fleischmann, Bernd K.
中科院分区：
文献类型：
--
作者：
Malan, Daniela;Reppel, Michael;Fleischmann, Bernd K.
层粘连蛋白形成细胞外基质（ECM）蛋白大家族，它们的表达是正常胚胎发育的先决条件。在此，我们使用来自缺乏 LAMC1 基因的胚胎干细胞的心肌细胞研究了层粘连蛋白 γ 1 链对心肌分化和功能的作用。层粘连蛋白 γ 1 (-/-) 心肌细胞缺乏基底膜 (BM)，但其肌节组织不受影响。因此，电活动和荷尔蒙调节被发现完好无损。然而，BM形成不足导致相邻心肌细胞之间ECM沉积增加，从而导致电信号传播缺陷。此外，我们还发现起搏器区域的数量有所增加。因此，虽然层粘连蛋白和完整的 BM 对于心肌细胞发育和分化本身并不是必需的，但它们是基质分子正常沉积所必需的，并且对于完整的电信号传播至关重要。干细胞2009； 27：88-99
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 gamma 1 chain for cardiac muscle differentiation and function using cardiomyocytes derived from embryonic stem cells deficient in the LAMC1 gene. Laminin gamma 1 (-/-) 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. STEM CELLS 2009; 27: 88-99