Stem Cell Reviews and Reports

, Volume 14, Issue 1, pp 71–81 | Cite as

MicroRNAs: Important Regulators of Induced Pluripotent Stem Cell Generation and Differentiation

  • Zhao-Lin Zeng
  • Xiao-long Lin
  • Li-Lan Tan
  • Ya-Mi Liu
  • Kai Qu
  • Zuo WangEmail author


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.


Induced 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.

Ethical Approval

This article does not contain any studies with human participants or animals performed by any of the authors.

Informed Consent

Informed consent was obtained from all individual participants included in the study.


  1. 1.
    Benjamin, E. J., Blaha, M. J., Chiuve, S. E., et al. (2017). Heart Disease and Stroke Statistics-2017 Update: A Report From the American Heart Association. Circulation, 135, e146–e603.CrossRefPubMedPubMedCentralGoogle Scholar
  2. 2.
    Zhang, X. H., Lu, Z. L., & Liu, L. (2008). Coronary heart disease in China, Heart, 94, 1126–1131.Google Scholar
  3. 3.
    Zhang, J., Wilson, G. F., Soerens, A. G., et al. (2009). Functional cardiomyocytes derived from human induced pluripotent stem cells. Circ. Res, 104, e30–e41.CrossRefPubMedPubMedCentralGoogle Scholar
  4. 4.
    Thomson, J. A., Itskovitz-Eldor, J., Shapiro, S. S., et al. (1998). Embryonic stem cell lines derived from human blastocysts. Science, 282, 1145–1147.CrossRefPubMedGoogle Scholar
  5. 5.
    Takahashi, K., & Yamanaka, S. (2006). Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors. Cell, 126, 663–676.CrossRefPubMedGoogle Scholar
  6. 6.
    Maherali, N., & Hochedlinger, K. (2008). Guidelines and techniques for the generation of induced pluripotent stem cells. Cell Stem Cell, 3, 595–605.CrossRefPubMedGoogle Scholar
  7. 7.
    Lo Sardo, V., Ferguson, W., Erikson, G. A., Topol, E. J., Baldwin, K. K., & Torkamani, A. (2017). Influence of donor age on induced pluripotent stem cells. Nat. Biotechnol, 35, 69–74.CrossRefPubMedGoogle Scholar
  8. 8.
    Feng, B., Ng, J. H., Heng, J. C., & Ng, H. H. (2009). Molecules that promote or enhance reprogramming of somatic cells to induced pluripotent stem cells. Cell Stem Cell, 4, 301–312.CrossRefPubMedGoogle Scholar
  9. 9.
    Melton, C., Judson, R. L., & Blelloch, R. (2010). Opposing microRNA families regulate self-renewal in mouse embryonic stem cells. Nature, 463, 621-U645.CrossRefGoogle Scholar
  10. 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
  11. 11.
    Gong, L., Pan, X., Chen, H., et al. (2016). p53 isoform Delta133p53 promotes efficiency of induced pluripotent stem cells and ensures genomic integrity during reprogramming. Sci. Rep, 6, 37281.CrossRefPubMedPubMedCentralGoogle Scholar
  12. 12.
    Di Stefano, B., Maffioletti, S. M., Gentner, B., et al. (2011). A microRNA-Based System for Selecting and Maintaining the Pluripotent State in Human Induced Pluripotent Stem Cells. Stem Cells, 29, 1684–1695.CrossRefPubMedGoogle Scholar
  13. 13.
    Worringer, K. A., Rand, T. A., Hayashi, Y., et al. (2014). The let-7/LIN-41 pathway regulates reprogramming to human induced pluripotent stem cells by controlling expression of prodifferentiation genes. Cell Stem Cell, 14, 40–52.CrossRefPubMedGoogle Scholar
  14. 14.
    Subramanyam, D., Lamouille, S., Judson, R. L., et al. (2011). Multiple targets of miR-302 and miR-372 promote reprogramming of human fibroblasts to induced pluripotent stem cells. Nat. Biotechnol, 29, 443–448.CrossRefPubMedPubMedCentralGoogle Scholar
  15. 15.
    Li, Z., Yang, C. S., Nakashima, K., & Rana, T. M. (2011). Small RNA-mediated regulation of iPS cell generation. EMBO J, 30, 823–834.CrossRefPubMedPubMedCentralGoogle Scholar
  16. 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
  17. 17.
    Anokye-Danso, F., Trivedi, C. M., Juhr, D., et al. (2011). Highly Efficient miRNA-Mediated Reprogramming of Mouse and Human Somatic Cells to Pluripotency. Cell Stem Cell, 8, 376–388.CrossRefPubMedPubMedCentralGoogle Scholar
  18. 18.
    Yu, J., Vodyanik, M. A., Smuga-Otto, K., et al. (2007). Induced pluripotent stem cell lines derived from human somatic cells. Science, 318, 1917–1920.CrossRefPubMedGoogle Scholar
  19. 19.
    Chen, I. Y., Matsa, E., & Wu, J. C. (2016). Induced pluripotent stem cells: at the heart of cardiovascular precision medicine. Nature Reviews Cardiology, 13, 333–349.CrossRefPubMedGoogle Scholar
  20. 20.
    Reardon, S., & Cyranoski, D. (2014). Japan stem-cell trial stirs envy. Nature, 513, 287–288.CrossRefPubMedGoogle Scholar
  21. 21.
    Scudellari, M. (2016). A DECADE OF iPS CELLS. Nature, 534, 310–312.CrossRefPubMedGoogle Scholar
  22. 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
  23. 23.
    Kuriyan, A. E., Albini, T. A., Townsend, J. H., et al. (2017). Vision Loss after Intravitreal Injection of Autologous “Stem Cells” for AMD, N. Engl. J. Med, 376, 1047–1053.CrossRefGoogle Scholar
  24. 24.
    Malan, D., Friedrichs, S., Fleischmann, B. K., & Sasse, P. (2011). Cardiomyocytes obtained from induced pluripotent stem cells with long-QT syndrome 3 recapitulate typical disease-specific features in vitro. Circ. Res, 109, 841–847.CrossRefPubMedGoogle Scholar
  25. 25.
    Micallef, S. J., Li, X., Schiesser, J. V., et al. (2012). INSGFP/w human embryonic stem cells facilitate isolation of in vitro derived insulin-producing cells. Diabetologia, 55, 694–706.CrossRefPubMedGoogle Scholar
  26. 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
  27. 27.
    Zhu, Y. X., Wu, X. M., Liang, Y. H., et al. (2016). Repair of cartilage defects in osteoarthritis rats with induced pluripotent stem cell derived chondrocytes. BMC Biotechnol, 16, 11.CrossRefGoogle Scholar
  28. 28.
    Soldner, F., Hockemeyer, D., Beard, C., et al. (2009). Parkinson’s disease patient-derived induced pluripotent stem cells free of viral reprogramming factors. Cell, 136, 964–977.CrossRefPubMedPubMedCentralGoogle Scholar
  29. 29.
    Judson, R. L., Babiarz, J. E., Venere, M., & Blelloch, R. (2009). Embryonic stem cell-specific microRNAs promote induced pluripotency. Nat. Biotechnol, 27, 459–461.CrossRefPubMedPubMedCentralGoogle Scholar
  30. 30.
    Selvaraj, V., Plane, J. M., Williams, A. J., & Deng, W. (2010). Switching cell fate: the remarkable rise of induced pluripotent stem cells and lineage reprogramming technologies. Trends Biotechnol, 28, 214–223.CrossRefPubMedPubMedCentralGoogle Scholar
  31. 31.
    Tian, Y. Y., Luo, A. P., Cai, Y. R., et al. (2010). MicroRNA-10b Promotes Migration and Invasion through KLF4 in Human Esophageal Cancer Cell Lines. J. Biol. Chem, 285, 7986–7994.CrossRefPubMedPubMedCentralGoogle Scholar
  32. 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. 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
  34. 34.
    Ben-David, U., & Benvenisty, N. (2011). The tumorigenicity of human embryonic and induced pluripotent stem cells. Nature Reviews Cancer, 11, 268–277.CrossRefPubMedGoogle Scholar
  35. 35.
    Lee, A. S., Tang, C., Rao, M. S., Weissman, I. L., & Wu, J. C. (2013). Tumorigenicity as a clinical hurdle for pluripotent stem cell therapies. Nat. Med, 19, 998–1004.CrossRefPubMedPubMedCentralGoogle Scholar
  36. 36.
    Xiao, X., Li, N., Zhang, D., Yang, B., Guo, H., & Li, Y. (2016). Generation of Induced Pluripotent Stem Cells with Substitutes for Yamanaka’s Four Transcription Factors. Cell Reprogram, 18, 281–297.CrossRefPubMedGoogle Scholar
  37. 37.
    Lian, X. J., Hsiao, C., Wilson, G., et al. (2012). Robust cardiomyocyte differentiation from human pluripotent stem cells via temporal modulation of canonical Wnt signaling. Proc. Natl. Acad. Sci. U. S. A, 109, E1848–E1857.CrossRefPubMedPubMedCentralGoogle Scholar
  38. 38.
    Shafiee, M., Aleyasin, S. A., Vasei, M., Semnani, S., & Mowla, S. J. (2016). Down-Regulatory Effects of miR-211 on Long Non-Coding RNA SOX2OT and SOX2 Genes in Esophageal Squamous Cell Carcinoma. Cell Journal, 17, 593–600.PubMedPubMedCentralGoogle Scholar
  39. 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
  40. 40.
    Huangfu, D. W., Maehr, R., Guo, W. J., et al. (2008). Induction of pluripotent stem cells by defined factors is greatly improved by small-molecule compounds. Nat. Biotechnol, 26, 795–797.CrossRefPubMedGoogle Scholar
  41. 41.
    Aasen, T., Raya, A., Barrero, M. J., et al. (2008). Efficient and rapid generation of induced pluripotent stem cells from human keratinocytes. Nat. Biotechnol, 26, 1276–1284.CrossRefPubMedGoogle Scholar
  42. 42.
    Deng, W., Cao, X., Chen, J., et al. (2015). MicroRNA Replacing Oncogenic Klf4 and c-Myc for Generating iPS Cells via Cationized Pleurotus eryngii Polysaccharide-based Nanotransfection. ACS Appl Mater Interfaces, 7, 18957–18966.CrossRefPubMedGoogle Scholar
  43. 43.
    Nakagawa, M., Koyanagi, M., Tanabe, K., et al. (2008). Generation of induced pluripotent stem cells without Myc from mouse and human fibroblasts. Nat. Biotechnol, 26, 101–106.CrossRefPubMedGoogle Scholar
  44. 44.
    Bao, X., Zhu, X., Liao, B., et al. (2013). MicroRNAs in somatic cell reprogramming. Curr. Opin. Cell Biol, 25, 208–214.CrossRefPubMedGoogle Scholar
  45. 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. 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
  47. 47.
    Krol, J., Loedige, I., & Filipowicz, W. (2010). The widespread regulation of microRNA biogenesis, function and decay. Nat Rev Genet, 11, 597–610.CrossRefPubMedGoogle Scholar
  48. 48.
    Bartel, D. P. (2009). MicroRNAs: target recognition and regulatory functions. Cell, 136, 215–233.CrossRefPubMedPubMedCentralGoogle Scholar
  49. 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. 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
  51. 51.
    Kawamura, T., Suzuki, J., Wang, Y. V., et al. (2009). Linking the p53 tumour suppressor pathway to somatic cell reprogramming. Nature, 460, 1140-U1107.CrossRefGoogle Scholar
  52. 52.
    Choi, Y. J., Lin, C. P., Ho, J. J., et al. (2011). miR-34 miRNAs provide a barrier for somatic cell reprogramming. Nat. Cell Biol, 13, 1353–1360.CrossRefPubMedPubMedCentralGoogle Scholar
  53. 53.
    He, L., He, X. Y., Lim, L. P., et al. (2007). A microRNA component of the p53 tumour suppressor network. Nature, 447, 1130-U1116.CrossRefGoogle Scholar
  54. 54.
    Chang, T. C., Wentzel, E. A., Kent, O. A., et al. (2007). Transactivation of miR-34a by p53 broadly influences gene expression and promotes apoptosis. Molecular Cell, 26, 745–752.CrossRefPubMedPubMedCentralGoogle Scholar
  55. 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. 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
  57. 57.
    Kondo, H., Kim, H. W., Wang, L., et al. (2016). Blockade of senescence-associated microRNA-195 in aged skeletal muscle cells facilitates reprogramming to produce induced pluripotent stem cells. Aging Cell, 15, 56–66.CrossRefPubMedGoogle Scholar
  58. 58.
    Ambasudhan, R., Talantova, M., Coleman, R., et al. (2011). Direct reprogramming of adult human fibroblasts to functional neurons under defined conditions. Cell Stem Cell, 9, 113–118.CrossRefPubMedPubMedCentralGoogle Scholar
  59. 59.
    Card, D. A. G., Hebbar, P. B., Li, L. P., et al. (2008). Oct4/Sox2-regulated miR-302 targets cyclin D1 in human embryonic stem cells. Mol. Cell. Biol, 28, 6426–6438.CrossRefPubMedGoogle Scholar
  60. 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
  61. 61.
    Kuo, C. H., Deng, J. H., Deng, Q., & Ying, S. Y. (2012). A novel role of miR-302/367 in reprogramming, Biochem. Biophys. Res. Commun, 417, 11–16.CrossRefGoogle Scholar
  62. 62.
    Koga, C., Kobayashi, S., Nagano, H., et al. (2014). Reprogramming Using microRNA-302 Improves Drug Sensitivity in Hepatocellular Carcinoma Cells. Ann. Surg. Oncol, 21, S591-S600.CrossRefGoogle Scholar
  63. 63.
    Lu, J., Dong, H. Y., Lin, L. J., Wang, Q. H., Huang, L. H., & Tan, J. M. (2014). miRNA-302 facilitates reprogramming of human adult hepatocytes into pancreatic islets-like cells in combination with a chemical defined media, Biochem. Biophys. Res. Commun, 453, 405–410.CrossRefGoogle Scholar
  64. 64.
    Miyoshi, N., Ishii, H., Nagano, H., et al. (2011). Reprogramming of mouse and human cells to pluripotency using mature microRNAs. Cell Stem Cell, 8, 633–638.CrossRefPubMedGoogle Scholar
  65. 65.
    Shaer, A., Azarpira, N., & Karimi, M. H. (2014). Differentiation of Human Induced Pluripotent Stem Cells into Insulin-Like Cell Clusters with miR-186 and miR-375 by using chemical transfection. Appl. Biochem. Biotechnol, 174, 242–258.CrossRefPubMedGoogle Scholar
  66. 66.
    Nomura, T., Kimura, M., Horii, T., et al. (2008). MeCP2-dependent repression of an imprinted miR-184 released by depolarization. Hum. Mol. Genet, 17, 1192–1199.CrossRefPubMedGoogle Scholar
  67. 67.
    Jiang, C., Qin, B., Liu, G. H., et al. (2016). MicroRNA-184 promotes differentiation of the retinal pigment epithelium by targeting the AKT2/mTOR signaling pathway. Oncotarget, 7, 52340–52353.PubMedPubMedCentralGoogle Scholar
  68. 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
  69. 69.
    Liu, T., Hou, L., Zhao, Y., & Huang, Y. (2015). Epigenetic silencing of HDAC1 by miR-449a upregulates Runx2 and promotes osteoblast differentiation. Int. J. Mol. Med, 35, 238–246.CrossRefPubMedGoogle Scholar
  70. 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
  71. 71.
    Ozeki, N., Hase, N., Hiyama, T., et al. (2017). MicroRNA-211 and autophagy-related gene 14 signaling regulate osteoblast-like cell differentiation of human induced pluripotent stem cells, Exp. Cell Res, 352, 63–74.CrossRefGoogle Scholar
  72. 72.
    Hall, V. (2008). Porcine embryonic stem cells: a possible source for cell replacement therapy. Stem Cell Rev, 4, 275–282.CrossRefPubMedGoogle Scholar
  73. 73.
    Ma, K., Song, G., An, X., et al. (2014). miRNAs promote generation of porcine-induced pluripotent stem cells. Mol. Cell. Biochem, 389, 209–218.CrossRefPubMedGoogle Scholar
  74. 74.
    Hara, E. S., Ono, M., Eguchi, T., et al. (2013). miRNA-720 controls stem cell phenotype, proliferation and differentiation of human dental pulp cells. PLoS One, 8, e83545.CrossRefPubMedPubMedCentralGoogle Scholar
  75. 75.
    Takaya, T., Nishi, H., Horie, T., Ono, K., & Hasegawa, K. (2012). Roles of microRNAs and myocardial cell differentiation. Prog. Mol. Biol. Transl. Sci, 111, 139–152.CrossRefPubMedGoogle Scholar
  76. 76.
    Gu, S., & Chan, W. Y. (2012). Flexible and Versatile as a Chameleon-Sophisticated Functions of microRNA-199a. Int. J. Mol. Sci, 13, 8449–8466.CrossRefPubMedPubMedCentralGoogle Scholar
  77. 77.
    Lee, Y. L., Peng, Q., Fong, S. W., et al. (2012). Sirtuin 1 facilitates generation of induced pluripotent stem cells from mouse embryonic fibroblasts through the miR-34a and p53 pathways. PLoS One, 7, e45633.CrossRefPubMedPubMedCentralGoogle Scholar
  78. 78.
    Yang, Y., Duan, W. X., Li, Y., et al. (2013). Novel Role of Silent Information Regulator 1 in Myocardial Ischemia. Circulation, 128, 2232–2240.CrossRefPubMedGoogle Scholar
  79. 79.
    Li, Z. B., Margariti, A., Wu, Y. T., et al. (2015). MicroRNA-199a induces differentiation of induced pluripotent stem cells into endothelial cells by targeting sirtuin 1. Mol. Med. Report, 12, 3711–3717.CrossRefGoogle Scholar
  80. 80.
    Calvanese, V., Lara, E., Suarez-Alvarez, B., et al. (2010). Sirtuin 1 regulation of developmental genes during differentiation of stem cells. Proc. Natl. Acad. Sci. U. S. A, 107, 13736–13741.CrossRefPubMedPubMedCentralGoogle Scholar
  81. 81.
    Cheng, B. B., Yan, Z. Q., Yao, Q. P., et al. (2012). Association of SIRT1 expression with shear stress induced endothelial progenitor cell differentiation. J. Cell. Biochem, 113, 3663–3671.CrossRefPubMedGoogle Scholar
  82. 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
  83. 83.
    Suchting, S., Freitas, C., le Noble, F., et al. (2007). The Notch ligand Delta-like 4 negatively regulates endothelial tip cell formation and vessel branching. Proc. Natl. Acad. Sci. U. S. A, 104, 3225–3230.CrossRefPubMedPubMedCentralGoogle Scholar
  84. 84.
    Yang, D., Wang, J., Xiao, M., Zhou, T., & Shi, X. (2016). Role of Mir-155 in Controlling HIF-1alpha Level and Promoting Endothelial Cell Maturation. Sci. Rep, 6, 35316.CrossRefPubMedPubMedCentralGoogle Scholar
  85. 85.
    Dimova, D. K., & Dyson, N. J. (2005). The E2F transcriptional network: old acquaintances with new faces. Oncogene, 24, 2810–2826.CrossRefPubMedGoogle Scholar
  86. 86.
    Zou, Z., Ocaya, P. A., Sun, H., Kuhnert, F., & Stuhlmann, H. (2010). Targeted Vezf1-null mutation impairs vascular structure formation during embryonic stem cell differentiation. Arterioscler. Thromb. Vasc. Biol, 30, 1378–1388.CrossRefPubMedPubMedCentralGoogle Scholar
  87. 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
  88. 88.
    Di Bernardini, E., Campagnolo, P., Margariti, A., et al. (2014). Endothelial lineage differentiation from induced pluripotent stem cells is regulated by microRNA-21 and transforming growth factor beta2 (TGF-beta2) pathways. J. Biol. Chem, 289, 3383–3393.CrossRefPubMedGoogle Scholar
  89. 89.
    Verhamme, F. M., Bracke, K. R., Joos, G. F., & Brusselle, G. G. (2015). Transforming Growth Factor-beta Superfamily in Obstructive Lung Diseases. Am. J. Respir. Cell Mol. Biol, 52, 653–662.CrossRefPubMedGoogle Scholar
  90. 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
  91. 91.
    Massague, J., Blain, S. W., & Lo, R. S. (2000). TGF beta signaling in growth control, cancer, and heritable disorders. Cell, 103, 295–309.CrossRefPubMedGoogle Scholar
  92. 92.
    Itoh, F., Itoh, S., Adachi, T., et al. (2012). Smad2/Smad3 in endothelium is indispensable for vascular stability via S1PR1 and N-cadherin expressions. Blood, 119, 5320–5328.CrossRefPubMedPubMedCentralGoogle Scholar
  93. 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
  94. 94.
    Wang, L. N., Su, W. J., Du, W., et al. (2015). Gene and MicroRNA Profiling of Human Induced Pluripotent Stem Cell-Derived Endothelial Cells. Stem Cell Reviews and Reports, 11, 219–227.CrossRefPubMedGoogle Scholar
  95. 95.
    Lu, T. Y., Lin, B., Li, Y., et al. (2013). Overexpression of microRNA-1 promotes cardiomyocyte commitment from human cardiovascular progenitors via suppressing WNT and FGF signaling pathways. J. Mol. Cell. Cardiol, 63, 146–154.CrossRefPubMedPubMedCentralGoogle Scholar
  96. 96.
    Pinson, K. I., Brennan, J., Monkley, S., Avery, B. J., & Skarnes, W. C. (2000). An LDL-receptor-related protein mediates Wnt signalling in mice. Nature, 407, 535–538.CrossRefPubMedGoogle Scholar
  97. 97.
    Kouhara, H., Hadari, Y. R., SpivakKroizman, T., et al. (1997). A lipid-anchored Grb2-binding protein that links FGF-receptor activation to the Ras/MAPK signaling pathway. Cell, 89, 693–702.CrossRefPubMedGoogle Scholar
  98. 98.
    Jayawardena, T. M., Egemnazarov, B., Finch, E. A., et al. (2012). MicroRNA-mediated in vitro and in vivo direct reprogramming of cardiac fibroblasts to cardiomyocytes. Circ. Res, 110, 1465–1473.CrossRefPubMedPubMedCentralGoogle Scholar
  99. 99.
    Itzhaki, I., Maizels, L., Huber, I., et al. (2011). Modelling the long QT syndrome with induced pluripotent stem cells. Nature, 471, 225-U113.CrossRefGoogle Scholar
  100. 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
  101. 101.
    Aoi, T., Yae, K., Nakagawa, M., et al. (2008). Generation of pluripotent stem cells from adult mouse liver and stomach cells. Science, 321, 699–702.CrossRefPubMedGoogle Scholar
  102. 102.
    Shi, Y., Zhao, Y., & Deng, H. K. (2010). Powering Reprogramming with Vitamin C. Cell Stem Cell, 6, 1–2.CrossRefPubMedGoogle Scholar
  103. 103.
    Ameres, S. L., & Zamore, P. D. (2013). Diversifying microRNA sequence and function. Nature Reviews Molecular Cell Biology, 14, 475–488.CrossRefPubMedGoogle Scholar
  104. 104.
    Barbuti, A., Benzoni, P., Campostrini, G., & Dell’Era, P. (2016). Human derived cardiomyocytes: A decade of knowledge after the discovery of induced pluripotent stem cells. Dev. Dyn, 245, 1145–1158.CrossRefPubMedGoogle Scholar
  105. 105.
    Guo, C., Deng, Y., Liu, J., & Qian, L. (2015). Cardiomyocyte-specific role of miR-24 in promoting cell survival. J. Cell. Mol. Med, 19, 103–112.CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2017

Authors and Affiliations

  1. 1.Institute of Cardiovascular Research, Key Laboratory for Atherosclerology of Hunan ProvinceUniversity of South ChinaHengyangChina
  2. 2.Department of Pathology, Huizhou Third People’s HospitalGuangzhou Medical UniversityHuizhouChina

Personalised recommendations