Differential gene expressions in atrial and ventricular myocytes: insights into the road of applying embryonic stem cell-derived cardiomyocytes for future therapies

Abstract

Ng SY, Wong CK, Tsang SY. Differential gene expressions in atrial and ventricular myocytes: insights into the road of applying embryonic stem cell-derived cardiomyocytes for future therapies. Am J Physiol Cell Physiol 299: C1234-C1249, 2010. First published September 15, 2010 doi:10.1152/ajpcell.00402.2009.-Myocardial infarction has been the leading cause of morbidity and mortality in developed countries over the past few decades. The transplantation of cardiomyocytes offers a potential method of treatment. However, cardiomyocytes are in high demand and their supply is extremely limited. Embryonic stem cells (ESCs), which have been isolated from the inner cell mass of blastocysts, can self-renew and are pluripotent, meaning they have the ability to develop into any type of cell, including cardiomyocytes. This suggests that ESCs could be a good source of genuine cardiomyocytes for future therapeutic purposes. However, problems with the yield and purity of ESC-derived cardiomyocytes, among other hurdles for the therapeutic application of ESCderived cardiomyocytes (e.g., potential immunorejection and tumor formation problems), need to be overcome before these cells can be used effectively for cell replacement therapy. ESC-derived cardiomyocytes consist of nodal, atrial, and ventricular cardiomyocytes. Specifically, for treatment of myocardial infarction, transplantation of a sufficient quantity of ventricular cardiomyocytes, rather than nodal or atrial cardiomyocytes, is preferred. Hence, it is important to find ways of increasing the yield and purity of specific types of cardiomyocytes. Atrial and ventricular cardiomyocytes have differential expression of genes (transcription factors, structural proteins, ion channels, etc.) and are functionally distinct. This paper presents a thorough review of differential gene expression in atrial and ventricular myocytes, their expression throughout development, and their regulation. An understanding of the molecular and functional differences between atrial and ventricular myocytes allows discussion of potential strategies for preferentially directing ESCs to differentiate into chamber-specific cells, or for fine tuning the ESC-derived cardiomyocytes into specific electrical and contractile phenotypes resembling chamber-specific cells.

Transcriptome of human foetal heart compared with cardiomyocytes from pluripotent stem cells

“…The volcano plots in Fig. 2C display the DEGs, with selected genes highlighted based on the results here and from earlier publications on the adult cardiac transcriptome (Ng et al, 2010;Lu et al, 2014).…”

How to make a cardiomyocyte

“…The electrical impulses converge on the AVN and spread through the ventricular conduction system (LBB, RBB, Purkinje cells), leading to a depolarization of the syncytium of cardiomyocytes, thereby ensuring orchestrated contraction of the chambers. Nodal, atrial and ventricular cardiomyocytes can be defined based on their location as well as their functional, molecular and electrophysiological properties (see table); the characteristic action potentials (APs) of cardiac myocyte subtypes are illustrated Bird et al, 2003;Bootman et al, 2011;Chandler et al, 2009;Gourdie et al, 1998;Greener et al, 2011;Hoogaars et al, 2007;Mikawa and Hurtado, 2007;Miquerol et al, 2011;Ng et al, 2010 hyperpolarization-activated cyclic nucleotide-gated channel 4; Tbx18/3, T-box transcription factor 18/3; Shox2, short stature homeobox 2; Lbh, limb bud and heart development transcription factor; sMHC, slow tonic myosin heavy chain; Nav1.1, voltage-gated sodium channel; NF-M, neurofilament-M. The specification of the cardiomyogenic lineage is a complex process governed by extracellular signaling pathways and a network of transcription factors.…”

Highly efficient derivation of ventricular cardiomyocytes from induced pluripotent stem cells with a distinct epigenetic signature

“…Neither pluripotent stem cells nor direct reprogramming methods address another critical issue, which is the need to generate chamber-specific cardiomyocytes. Pacemaker, atrial, and ventricular myocytes (VMs) have distinct functional and electrophysiological properties that may contribute to cardiac arrhythmias in the wrong environment [7,8] yield a heterogeneous population of cardiomyocytes of which only 30% -70% are VMs [9,10], and methods of purifying VMs from a population of stem cell-derived cardiomyocytes remain to be established. These issues underscore the need to better understand the molecular pathways that govern the specification of VMs from pluripotent stem cells.…”