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TBX18 transcription factor overexpression in human-induced pluripotent stem cells increases their differentiation into pacemaker-like cells
Authors
N. Aghdami
A. Atashi
+8 more
A.M. Gorabi
S. Hajighasemi
V. Khori
Y. Panahi
A.K. Saeid
A. Sahebkar
M. Soleimani
H.A. Tafti
Publication date
1 January 2018
Publisher
Wiley-Liss Inc.
Abstract
Background: The discovery of gene- and cell-based strategies has opened a new area to investigate novel approaches for the treatment of many conditions caused by cardiac cell failure. The TBX18 (T-box 18) transcription factor is considered as a prominent factor in the sinoatrial node (SAN) formation during the embryonic development. In this in vitro study, the effect of TBX18 gene expression on human-induced pluripotent-stem-cell-derived cardiomyocytes (hiPS-CMs) to induce pacemaker-like cells was examined. Methods: The human-dermal-fibroblast-derived iPSCs were transfected using chemical, physical, and Lentiviral methods of TBX18 gene delivery during differentiation into cardiomyocytes (CMs). After the differentiation process through small-molecule-based temporal modulation of the Wnt signaling pathway, the hiPSC-CMs were analyzed using the real-time polymerase chain reaction, immunocytochemistry, immunofluorescence, whole-cell patch-clamp recording, and western blotting to investigate the accuracy of differentiation and identify the effect exerted by TBX18. Results: The hiPS-CMs showed spontaneous beating and expressed specific markers of cardiac cells. The lentiviral-mediated TBX18 delivery was the most efficient method for transfection. The results showed the increment in Connexin 43 expression among untransfected hiPS-CMs, whereas this protein was significantly downregulated followed by TBX18 overexpression. TBX18-hiPSCMs were detected with pacemaker cell features. Conclusions: It was demonstrated that the TBX18 gene is able to conduct hiPSCs to differentiate into pacemaker-like cells. The TBX18 gene delivery seems to have the potential for the development of biological pacemakers; however, more investigations are still needed to assess its usefulness to fix arrhythmic conditions with SAN failure basis. © 2018 Wiley Periodicals, Inc
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Golestan University of Medical Sciences Repository
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oai:eprints.goums.ac.ir:10392
Last time updated on 16/12/2019
Golestan University of Medical Sciences Repository
See this paper in CORE
Go to the repository landing page
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oai:eprints.goums.ac.ir:9645
Last time updated on 07/01/2019