Golestan University of Medical Sciences Repository

TBX18 transcription factor overexpression in human-induced pluripotent stem cells increases their differentiation into pacemaker-like cells

Gorabi, A.M. and Hajighasemi, S. and Tafti, H.A. and Atashi, A. and Soleimani, M. and Aghdami, N. and Saeid, A.K. and Khori, V. and Panahi, Y. and Sahebkar, A. (2019) TBX18 transcription factor overexpression in human-induced pluripotent stem cells increases their differentiation into pacemaker-like cells. Journal of Cellular Physiology, 234 (2). pp. 1534-1546.

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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.

Item Type: Article
Additional Information: cited By 3
Uncontrolled Keywords: complementary DNA; connexin 43; lentivirus vector; lipofectamine; transcription factor; transcription factor tbx18; unclassified drug, animal cell; Article; cardiac muscle cell; cell differentiation; diagnostic accuracy; DNA packaging; DNA synthesis; DNA transfection; down regulation; embryo; embryo development; gene delivery system; gene expression; gene overexpression; HEK293T cell line; human; human cell; immunocytochemistry; immunofluorescence; immunohistochemistry; in vitro study; induced pluripotent stem cell; mouse; nonhuman; pacemaker nerve cell; pluripotent stem cell; priority journal; quality control; real time polymerase chain reaction; RNA extraction; sinus node; Western blotting; whole cell patch clamp; Wnt signaling
Subjects: QS آناتومی انسان
QTفیزیولوژی
QU بیوشیمی
آسیب شناسی QZ
مقالات نمایه شده محققین دانشگاه در سایت ,Web of Science ,Scopus
Divisions: معاونت تحقیقات و فناوری
Depositing User: GOUMS
Date Deposited: 15 Dec 2019 11:31
Last Modified: 15 Dec 2019 11:31
URI: http://eprints.goums.ac.ir/id/eprint/10392

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