Preprint Article Version 1 This version is not peer-reviewed

S-Phase Synchronization Facilitates the Early Progression of Induced-Cardiomyocyte Reprogramming through Enhanced Cell-Cycle Exit

Version 1 : Received: 16 March 2018 / Approved: 21 March 2018 / Online: 21 March 2018 (05:29:25 CET)

A peer-reviewed article of this Preprint also exists.

Bektik, E.; Dennis, A.; Pawlowski, G.; Zhou, C.; Maleski, D.; Takahashi, S.; Laurita, K.R.; Deschênes, I.; Fu, J.-D. S-phase Synchronization Facilitates the Early Progression of Induced-Cardiomyocyte Reprogramming through Enhanced Cell-Cycle Exit. Int. J. Mol. Sci. 2018, 19, 1364. Bektik, E.; Dennis, A.; Pawlowski, G.; Zhou, C.; Maleski, D.; Takahashi, S.; Laurita, K.R.; Deschênes, I.; Fu, J.-D. S-phase Synchronization Facilitates the Early Progression of Induced-Cardiomyocyte Reprogramming through Enhanced Cell-Cycle Exit. Int. J. Mol. Sci. 2018, 19, 1364.

Journal reference: Int. J. Mol. Sci. 2018, 19, 1364
DOI: 10.3390/ijms19051364

Abstract

Direct reprogramming of fibroblasts into induced cardiomyocytes (iCMs) holds a great promise for regenerative medicine and has been studied in several major directions. However, cell-cycle regulation, a fundamental biological process, has not been investigated during iCM-reprogramming. Here, our time-lapse imaging on iCMs, reprogrammed by Gata4, Mef2c, and Tbx5 (GMT) monocistronic retroviruses, revealed that iCM-reprogramming was majorly initiated at late-G1- or S-phase and nearly half of GMT-reprogrammed iCMs divided soon after reprogramming. iCMs exited cell cycle along the process of reprogramming with decreased percentage of EdU+/αMHC-GFP+ cells. S-phase synchronization post-GMT-infection could enhance cell-cycle exit of reprogrammed iCMs and yield more GFPhigh iCMs, which achieved an advanced reprogramming with more expression of cardiac genes than GFPlow cells; however, S-phase synchronization didn’t enhance the polycistronic-MGT reprogramming, in which cell-cycle exit had been accelerated. In conclusion, post-infection synchronization of S-phase facilitated the early progression of GMT-reprogramming through a mechanism of enhanced cell-cycle exit.

Subject Areas

induced cardiomyocyte; epigenetic reprogramming; cell division; cell-cycle synchronization; cell-cycle exit

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