S-phase synchronization facilitates the early progression of induced-cardiomyocyte reprogramming through enhanced cell-cycle exit

Research output: Contribution to journalArticle

Authors

External Institution(s)

  • Case Western Reserve University
  • University of Tsukuba

Details

Original languageEnglish (US)
Article number1364
JournalInternational journal of molecular sciences
Volume19
Issue number5
StatusPublished - May 4 2018
Peer-reviewedYes

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 5-ethynyl-20-deoxyuridine (EdU)+/α-myosin heavy chain (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 did not enhance the reprogramming with a polycistronic-viral vector, 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.

    Research areas

  • Cell division, Cell-cycle exit, Cell-cycle synchronization, Epigenetic reprogramming, Induced cardiomyocyte

Citation formats

APA

Bektik, E., Dennis, A., Pawlowski, G., Zhou, C., Maleski, D., Takahashi, S., ... Fu, J. D. (2018). S-phase synchronization facilitates the early progression of induced-cardiomyocyte reprogramming through enhanced cell-cycle exit. International journal of molecular sciences, 19(5), [1364]. https://doi.org/10.3390/ijms19051364

Harvard

Bektik, E, Dennis, A, Pawlowski, G, Zhou, C, Maleski, D, Takahashi, S, Laurita, KR, Deschênes, I & Fu, JD 2018, 'S-phase synchronization facilitates the early progression of induced-cardiomyocyte reprogramming through enhanced cell-cycle exit', International journal of molecular sciences, vol. 19, no. 5, 1364. https://doi.org/10.3390/ijms19051364