Canonical Wnt signaling promotes pacemaker cell specification of cardiac mesodermal cells derived from mouse and human embryonic stem cells

• DOI: 10.1002/stem.3106
• Publication Date: 2019-10-24T18:05:33Z
• Authors: Wenbin Liang; Pengcheng Han; Elizabeth H. Kim; Jordan Mak; Rui Zhang; Angelo G. Torrente; Joshua I. Goldhaber; Eduardo Marbán; Hee Cheol Cho
• Keywords: Cardiac pacemaker; Beta-catenin; Pacemaker potential

Abstract Cardiac differentiation of embryonic stem cells (ESCs) can give rise to de novo chamber cardiomyocytes and nodal pacemaker cells. Compared with our understanding direct toward atrial ventricular myocytes, the mechanisms for cell commitment are not well understood. Taking a cue from prominence canonical Wnt signaling during cardiac tissue development in chick embryos, we asked if modulations influence progenitors bifurcate either or Omitting an exogenous inhibitor, which is routinely added maximize myocyte yield mouse human ESCs, led increased spontaneously beating action potential properties similar those native sinoatrial node The phenotype was accompanied by enhanced expression genes gene products that mark such as Hcn4, Tbx18, Tbx3, Shox2. Addition Wnt3a ligand, activates Wnt/β-catenin signaling, pacemaker-like myocytes while reducing cTNT-positive pan-cardiac differentiation. Conversely, addition inhibitors lineage at expense specification. positive impact on evidenced two ESC lines induced pluripotent Our data identify pathway critical determinant subtype differentiation: endogenous favors lineage, whereas its suppression promotes cardiomyocyte lineage.