Moore Jennifer C, Tsang Suk-Ying, Rushing Stephanie N, Lin Dawei, Tse Hung Fat, Chan Camie W Y, Li Ronald A
Department of Cell Biology & Human Anatomy, University of California, Davis Shriners Hospital, Sacramento, CA 95817, USA.
Biochem Biophys Res Commun. 2008 Dec 5;377(1):46-51. doi: 10.1016/j.bbrc.2008.09.076. Epub 2008 Sep 25.
Gap junctions, encoded by the connexin (Cx) multi-gene family, couple adjacent cells and underlie cell-cell communications. Previous mouse studies suggest that Cxs play an important role in development but their role in human cardiogenesis is undefined. Human embryonic stem cells (hESC) provide a unique model for studying human differentiation. Lentivirus-mediated stable overexpression of Cx43 in hESC (Cx43-hESC) did not affect colony morphology, karyotype and expression of pluripotency genes such as Oct4 but completely suppressed the formation of spontaneously beating, cardiomyocyte-containing clusters in embryoid bodies (EBs). Unlike control hEBs, the transcripts of several mesodermal markers (kallikrein, delta-globin, and CMP), ventricular myosin light chain and cardiac troponin I were absent or delayed. Transcriptomic and pathway analyses showed that 194 genes crucial for movement, growth, differentiation and maintenance were differentially expressed in Cx43-hESC. We conclude that Cx43 mediates the expression of an array of genes involved in human cardiogenesis, in addition to intercellular communication.
间隙连接由连接蛋白（Cx）多基因家族编码，连接相邻细胞，是细胞间通讯的基础。先前的小鼠研究表明，Cx在发育过程中起重要作用，但其在人类心脏发生中的作用尚不清楚。人类胚胎干细胞（hESC）为研究人类分化提供了独特的模型。慢病毒介导的hESC中Cx43的稳定过表达（Cx43-hESC）不影响集落形态、核型以及多能性基因如Oct4的表达，但完全抑制了胚状体（EBs）中自发跳动的含心肌细胞簇的形成。与对照hEBs不同，几种中胚层标志物（激肽释放酶、δ-珠蛋白和CMP）、心室肌球蛋白轻链和心肌肌钙蛋白I的转录本缺失或延迟出现。转录组学和通路分析表明，194个对运动、生长、分化和维持至关重要的基因在Cx43-hESC中差异表达。我们得出结论，Cx43除了介导细胞间通讯外，还介导一系列参与人类心脏发生的基因的表达。
