S-phase Synchronization Facilitates the Early Progression of Induced-Cardiomyocyte Reprogramming through Enhanced Cell-Cycle Exit.
S-phase Synchronization Facilitates the Early Progression of Induced-Cardiomyocyte Reprogramming through Enhanced Cell-Cycle Exit.
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DOI：
10.3390/ijms19051364
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发表时间：
2018-05-04
影响因子：
5.6
通讯作者：
Fu JD
中科院分区：
文献类型：
--
作者：
Bektik E;Dennis A;Pawlowski G;Zhou C;Maleski D;Takahashi S;Laurita KR;Deschênes I;Fu JD
将成纤维细胞直接重编程为诱导心肌细胞 (iCM) 为再生医学带来了巨大的希望，并已在多个主要方向进行了研究。然而，细胞周期调节这一基本的生物过程在 iCM 重编程过程中尚未得到研究。在这里，我们对由 Gata4、Mef2c 和 Tbx5 (GMT) 单顺反子逆转录病毒重编程的 iCM 进行延时成像，显示 iCM 重编程主要在 G1 或 S 期晚期启动，近一半的 GMT 重编程 iCM 在重编程后不久就分裂。 iCM 在重编程过程中退出细胞周期，其中 5-乙炔基-20-脱氧尿苷 (EdU)+/α-肌球蛋白重链 (αMHC)-GFP+ 细胞的百分比下降。 GMT 感染后的 S 期同步可以增强重编程 iCM 的细胞周期退出，并产生更多 GFPhigh iCM，从而实现了高级重编程，比 GFPlow 细胞表达更多心脏基因。然而，S期同步并没有增强多顺反子病毒载体的重编程，其中细胞周期退出被加速。总之，感染后 S 期同步通过增强细胞周期退出机制促进了 GMT 重编程的早期进展。
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.
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影响因子：
16.6
作者：
Zhao Y;Londono P;Cao Y;Sharpe EJ;Proenza C;O'Rourke R;Jones KL;Jeong MY;Walker LA;Buttrick PM;McKinsey TA;Song K
通讯作者：
Song K
DOI：
10.1038/nrg3473
发表时间：
2013-06
期刊：
Nature reviews. Genetics
影响因子：
--
作者：
通讯作者：
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影响因子：
64.8
作者：
Qian, Li;Huang, Yu;Srivastava, Deepak
通讯作者：
Srivastava, Deepak
影响因子：
14.8
作者：
Rosner, Margit;Schipany, Katharina;Hengstschlaeger, Markus
通讯作者：
Hengstschlaeger, Markus
通过对心脏转录因子的非肌细胞进行重编程通过重编程。
影响因子：
64.8
作者：
Song, Kunhua;Nam, Young-Jae;Luo, Xiang;Qi, Xiaoxia;Tan, Wei;Huang, Guo N.;Acharya, Asha;Smith, Christopher L.;Tallquist, Michelle D.;Neilson, Eric G.;Hill, Joseph A.;Bassel-Duby, Rhonda;Olson, Eric N.
通讯作者：
Olson, Eric N.