MicroRNAs: Important Regulators of Induced Pluripotent Stem Cell Generation and Differentiation
- 824 Downloads
Induced pluripotent stem (iPS) cells can differentiate into nearly all types of cells. In contrast to embryonic stem cells, iPS cells are not subject to immune rejection because they are derived from a patient’s own cells without ethical concerns. These cells can be used in regenerative medical techniques, stem cell therapy, disease modelling and drug discovery investigations. However, this application faces many challenges, such as low efficiency, slow generation time, partially reprogrammed colonies and tumourigenicity. Numerous techniques have been formulated in the past decade to improve reprogramming efficiency and safety, including the use of different transcription factors, small molecule compounds and non-coding RNAs. Recently, microRNAs (miRNAs) were found to promote the generation and differentiation of iPS cells. The miRNAs can more effectively and safely generate iPS cells than transcription factors. This process ultimately leads to the development of iPSC-based therapeutics for future clinical applications. In this comprehensive review, we summarise advances in research and the application of iPS cells, as well as recent progress in the use of miRNAs for iPS cell generation and differentiation. We examine possible clinical applications, especially in cardiology.
KeywordsInduced pluripotent stem cell MicroRNA Generation Differentiation
This study was supported by the Natural Science Foundation of China (No. 81070221; 81600342) and the Innovative Research Team for Science and Technology in Higher Educational Institutions of Hunan Province and the Construct Program of the Key Discipline in Hunan Province (No. 15C1201).
Compliance with Ethical Standards
Conflict of Interest
The authors declare that they have no conflict of interest.
This article does not contain any studies with human participants or animals performed by any of the authors.
Informed consent was obtained from all individual participants included in the study.
- 2.Zhang, X. H., Lu, Z. L., & Liu, L. (2008). Coronary heart disease in China, Heart, 94, 1126–1131.Google Scholar
- 10.Zhou, J. X., Su, P., Li, D., Tsang, S., Duan, E. K., & Wang, F. High-Efficiency Induction of Neural Conversion in Human ESCs and Human Induced Pluripotent Stem Cells with a Single Chemical Inhibitor of Transforming Growth Factor Beta Superfamily Receptors, Stem Cells. 28 (2010)1741–1750.Google Scholar
- 16.Clark, E. A., Kalomoiris, S., Nolta, J. A., & Fierro, F. A. Concise Review: MicroRNA Function in Multipotent Mesenchymal Stromal Cells, Stem Cells. 32 (2014)1074–1082.Google Scholar
- 22.Mandai, M., Watanabe, A., Kurimoto, Y., et al. (2017). Autologous Induced Stem-Cell–Derived Retinal Cells for Macular Degeneration, N. Engl. J. Med, 376, 1038–1046.Google Scholar
- 26.Mizumoto, H., Matsushita, S., & Kajiwara, T. (2016). Generation Of Functional Hepatocyte-like Cells From Human Induced Pluripotent Stem Cells In A Three-dimensional Culture Using Hollow Fibers. Tissue Engineering Part A, 22, S76-S76.Google Scholar
- 32.Lambertini, C., Pantano, S., & Dotto, G. P. Differential Control of Notch1 Gene Transcription by Klf4 and Sp3 Transcription Factors in Normal versus Cancer-Derived Keratinocytes., PLoS One. 5 (2010).Google Scholar
- 33.Wang, Y. J., Meng, L., Hu, H. Y., et al. (2011). Oct-4B isoform is differentially expressed in breast cancer cells: hypermethylation of regulatory elements of Oct-4A suggests an alternative promoter and transcriptional start site for Oct-4B transcription. Biosci. Rep, 31, 109–115.CrossRefPubMedGoogle Scholar
- 39.Mali, P., Chou, B. K., Yen, J., et al., Butyrate Greatly Enhances Derivation of Human Induced Pluripotent Stem Cells by Promoting Epigenetic Remodeling and the Expression of Pluripotency-Associated Genes, Stem Cells. 28 (2010)713–720.Google Scholar
- 45.Kim, J. B., Greber, B., Arauzo-Bravo, M. J., et al., Direct reprogramming of human neural stem cells by OCT4, Nature. 461 (2009)649-U693.Google Scholar
- 46.Brouwer, M., Zhou, H., & Nadif Kasri N. (2016). Choices for induction of pluripotency: Recent developments in human induced pluripotent stem cell reprogramming strategies. Stem Cell Rev, 12, 54–72.Google Scholar
- 49.Qu, K., Wang, Z., Lin, X. L., Zhang, K., He, X. L., & Zhang, H. MicroRNAs: Key regulators of endothelial progenitor cell functions., Clinica Chimica Acta. 448 (2015)65–73.Google Scholar
- 50.Ye, D., Wang, G. Y., Liu, Y., et al. (2012). miR-138 Promotes Induced Pluripotent Stem Cell Generation through the Regulation of the p53 Signaling (vol 30, pg 1645. Stem Cells, 31, (2013)2585–2586.Google Scholar
- 55.Choi, Y. J., Lin, C.-P., Risso, D., et al., Deficiency of microRNA miR-34a expands cell fate potential in pluripotent stem cells., Science (New York). 355 (2017).Google Scholar
- 56.Li, Z., & Rana, T. M. Using microRNAs to enhance the generation of induced pluripotent stem cells., Curr. Protoc. Stem Cell Biol. Chapter 4 (2012)Unit 4A 4.Google Scholar
- 60.Hu, S. J., Wilson, K. D., Ghosh, Z., et al., MicroRNA-302 Increases Reprogramming Efficiency via Repression of NR2F2, Stem Cells. 31 (2013)259–268.Google Scholar
- 68.Liu, L. L., Lu, S. X., Li, M., et al., FoxD3-regulated microRNA-137 suppresses tumour growth and metastasis in human hepatocellular carcinoma by targeting AKT2, Oncotarget. 5 (2014)5113–5124.Google Scholar
- 70.Nishimura, R., Wakabayashi, M., Hata, K., et al. (2012). Osterix Regulates Calcification and Degradation of Chondrogenic Matrices through Matrix Metalloproteinase 13 (MMP13) Expression in Association with Transcription Factor Runx2 during Endochondral Ossification. J. Biol. Chem, 287, 33179–33190.CrossRefPubMedPubMedCentralGoogle Scholar
- 82.Chen, T., Margariti, A., Kelaini, S., et al., MicroRNA-199b Modulates Vascular Cell Fate During iPS Cell Differentiation by Targeting the Notch Ligand Jagged1 and Enhancing VEGF Signaling, Stem Cells. 33 (2015)1405–1418.Google Scholar
- 87.Liang, J., Huang, W., Cai, W., et al., Inhibition of microRNA-495 Enhances Therapeutic Angiogenesis of Human Induced Pluripotent Stem Cells, Stem Cells. 35 (2017)337–350.Google Scholar
- 90.Vargel, O., Zhang, Y., Kosim, K., et al., Activation of the TGF beta pathway impairs endothelial to haematopoietic transition., Sci. Rep. 6 (2016).Google Scholar
- 93.Liu, H., Zhang, S., Zhao, L., et al., Resveratrol Enhances Cardiomyocyte Differentiation of Human Induced Pluripotent Stem Cells through Inhibiting Canonical WNT Signal Pathway and Enhancing Serum Response Factor-miR-1 Axis., Stem Cells Int. 2016 (2016)2524092.Google Scholar
- 100.Yazawa, M., Hsueh, B., Jia, X. L., et al., Using induced pluripotent stem cells to investigate cardiac phenotypes in Timothy syndrome., Nature. 471 (2011)230-U120.Google Scholar