NODAL inhibition promotes differentiation of pacemaker-like cardiomyocytes from human induced pluripotent stem cells
Year: 2020
Type: article
Abstract: Directed cardiomyogenesis from human induced pluripotent stem cells (hiPSCs) has been greatly improved in the last decade but directed differentiation to pacemaking cardiomyocytes (CMs) remains incompletely understood. In this study, we demonstrated that inhibition of NODAL signaling by a specific NODAL inhibitor (SB431542) in the cardiac mesoderm differentiation stage downregulated PITX2c, a transcription factor that is known to inhibit the formation of the sinoatrial node in the left atrium during cardiac development. The resulting hiPSC-CMs were smaller in cell size, expressed higher pro-pacemaking transcription factors, TBX3 and TBX18, and exhibited pacemaking-like electrophysiological characteristics compared to control hiPSC-CMs differentiated from established Wnt-based protocol. The pacemaker-like subtype increased up to 2.4-fold in hiPSC-CMs differentiated with the addition of SB431542 relative to the control. Hence, Nodal inhibition in the cardiac mesoderm stage promoted pacemaker-like CM differentiation from hiPSCs. Improving the yield of human pacemaker-like CMs is a critical first step in the development of functional human cell-based biopacemakers.
Source: Stem Cell Research
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $2,100
Awards: G1185946596, Nonlinear Optical Based Flow Cytometry for Purifying Stem Cell Derived Cardiomyocytes, G1508866, Functional interactions of cardiac ion channels, G2089753221, G249825309, G2536180224, Training Program in Basic and Translational Cardiovascular Science, G3444963248, G3549828030, G355879893, G3584208489, G416367201, G4165162335, Decoding the enigma of cardiac amplification, G5067448200, G5111225313, G5245285450, G5496526517, G5623463501, G6147201050, G6466435546, G6724624726, G6748234945, G6791343460, G6851052146, G6947823565, Functional Regulation of Cardiac Chloride Homeostasis, Translational Study of Cardiac Dysfunction, Development Of Novel Upstream Target For Atrial Fibrillation, G9000007450, G9000037102, G9000138392, G9000143267, G9000161668, G9000222575, G9000247267, G900591525
OpenAlex ID: W3091799212