Differentiation of Atrial Cardiomyocytes from Pluripotent Stem Cells Using the BMP Antagonist Grem2

Bylund, Jeffery B.; Hatzopoulos, Antonis K.

doi:10.3791/53919-v

Cited by 1 publication

(2 citation statements)

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“…GREM2 treatment also increased expression of Tnnt2, Gata4, Myl7, Gja5, Kcnj5 and Hey1 compared to control. Whereas, GREM2 treatment decreased expression of more ventricular transcripts such as Myl2, Gja1 and Kcnq1 Bylund [ 34 ] increased % contracting cells, and increased number of CPCs not shown not shown increases expression of NKX2.5 , MYH6 , TNNT2 and MYL7 . GREM2 effect was JNK-dependent GREM2 and RA Ahmad (this paper) elongated rod-like morphology in some, with organized striated sarcomeres.…”

Section: Resultsmentioning

confidence: 99%

“…RA has separately been shown to influence heart development, by actions that are thought to involve modification of BMP signalling [51]. Currently, a range of RA-based protocols exist for iPSC/ESC differentiation into atrial CMs and similarly for Gremlin 2 [8][9][10]12,13,19,33,34,52,53] (table 1). While these differentiation protocols have shown success in establishing an atrial-like phenotype, they mostly produced immature cells, particularly in terms of electrophysiology and pharmacology.…”

Section: Discussionmentioning

confidence: 99%

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Generation of cardiomyocytes from human-induced pluripotent stem cells resembling atrial cells with ability to respond to adrenoceptor agonists

Ahmad

Jin

Grassam-Rowe

et al. 2023

Phil. Trans. R. Soc. B

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Atrial fibrillation (AF) is the most common chronic arrhythmia presenting a heavy disease burden. We report a new approach for generating cardiomyocytes (CMs) resembling atrial cells from human-induced pluripotent stem cells (hiPSCs) using a combination of Gremlin 2 and retinoic acid treatment. More than 40% of myocytes showed rod-shaped morphology, expression of CM proteins (including ryanodine receptor 2, α -actinin-2 and F-actin) and striated appearance, all of which were broadly similar to the characteristics of adult atrial myocytes (AMs). Isolated myocytes were electrically quiescent until stimulated to fire action potentials with an AM profile and an amplitude of approximately 100 mV, arising from a resting potential of approximately −70 mV. Single-cell RNA sequence analysis showed a high level of expression of several atrial-specific transcripts including NPPA , MYL7 , HOXA3 , SLN , KCNJ4 , KCNJ5 and KCNA5 . Amplitudes of calcium transients recorded from spontaneously beating cultures were increased by the stimulation of α -adrenoceptors (activated by phenylephrine and blocked by prazosin) or β -adrenoceptors (activated by isoproterenol and blocked by CGP20712A). Our new approach provides human AMs with mature characteristics from hiPSCs which will facilitate drug discovery by enabling the study of human atrial cell signalling pathways and AF. This article is part of the theme issue ‘The heartbeat: its molecular basis and physiological mechanisms’.

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