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 JBiSE  Vol.9 No.4 , March 2016
MicroRNAs as Modulators of Endothelial Differentiation of Stem Cells
Abstract: MicroRNAs (miRs) are a class of small (~22 nucleotides), widely distributed, and highly conserved non-coding RNA molecules and play an important post-transcriptional regulatory role by targeting mRNA. Embryonic and induced pluripotent stem cells (ESCs and iPSC, respectively) hold great promise for vascular regenerative therapies. However, several limitations currently prohibit their therapeutic use. The importance of miRs in controlling the gene expression profile of a particular cell type is emerging and a multitude of miRs have been identified that play key roles in vascular development and regeneration. A combination of pluripotency transcription factors and different miRs not only enhances the pluripotency of stem cells but also has been reported to enhance their endothelial differentiation. This review will summarize the findings that focus different miR clusters in the induction, maintenance, and directed endothelial differentiation of ESCs and iPSCs.
Cite this paper: Gündüz, D. and Aslam, M. (2016) MicroRNAs as Modulators of Endothelial Differentiation of Stem Cells. Journal of Biomedical Science and Engineering, 9, 177-190. doi: 10.4236/jbise.2016.94014.
References

[1]   Mehta, D. and Malik, A.B. (2006) Signaling Mechanisms Regulating Endothelial Permeability. Physiological Reviews, 86, 279-367.
http://dx.doi.org/10.1152/physrev.00012.2005

[2]   Gaengel, K., Genove, G., Armulik, A. and Betsholtz, C. (2009) Endothelial-Mural Cell Signaling in Vascular Development and Angiogenesis. Arteriosclerosis, Thrombosis, and Vascular Biology, 29, 630-638.
http://dx.doi.org/10.1161/ATVBAHA.107.161521

[3]   Marcelo, K.L., Goldie, L.C. and Hirschi, K.K. (2013) Regulation of Endothelial Cell Differentiation and Specification. Circulation Research, 112, 1272-1287.
http://dx.doi.org/10.1161/CIRCRESAHA.113.300506

[4]   Fish, J.E. and Wythe, J.D. (2015) The Molecular Regulation of Arteriovenous Specification and Maintenance. Developmental Dynamics, 244, 391-409.
http://dx.doi.org/10.1002/dvdy.24252

[5]   Fadini, G.P., Losordo, D. and Dimmeler, S. (2012) Critical Reevaluation of Endothelial Progenitor Cell Phenotypes for Therapeutic and Diagnostic Use. Circulation Research, 110, 624-637.
http://dx.doi.org/10.1161/CIRCRESAHA.111.243386

[6]   Zhou, Y., Yang, F., Yang, M., Xiao, Q. and Zhang, L. (2014) MicroRNAs in Endothelial Development and Differentiation. Stem Cell Research & Therapy, 4, 1000191.

[7]   Lewis, B.P., Burge, C.B. and Bartel, D.P. (2005) Conserved Seed Pairing, Often Flanked by Adenosines, Indicates That Thousands of Human Genes Are microRNA Targets. Cell, 120, 15-20.
http://dx.doi.org/10.1016/j.cell.2004.12.035

[8]   He, L. and Hannon, G.J. (2004) MicroRNAs: Small RNAs with a Big Role in Gene Regulation. Nature Reviews Genetics, 5, 522-531.
http://dx.doi.org/10.1038/nrg1379

[9]   Lee, Y., Jeon, K., Lee, J.T., Kim, S. and Kim, V.N. (2002) MicroRNA Maturation: Stepwise Processing and Subcellular Localization. EMBO Journal, 21, 4663-4670.
http://dx.doi.org/10.1093/emboj/cdf476

[10]   Ha, M. and Kim, V.N. (2014) Regulation of microRNA Biogenesis. Nature Reviews Molecular Cell Biology, 15, 509- 524.
http://dx.doi.org/10.1038/nrm3838

[11]   Pratt, A.J. and MacRae, I.J. (2009) The RNA-Induced Silencing Complex: A Versatile Gene-Silencing Machine. The Journal of Biological Chemistry, 284, 17897-17901.
http://dx.doi.org/10.1074/jbc.R900012200

[12]   Verdel, A., Jia, S., Gerber, S., Sugiyama, T., Gygi, S., Grewal, S.I. and Moazed, D. (2004) RNAi-Mediated Targeting of Heterochromatin by the RITS Complex. Science, 303, 672-676.
http://dx.doi.org/10.1126/science.1093686

[13]   Buhler, M., Verdel, A. and Moazed, D. (2006) Tethering RITS to a Nascent Transcript Initiates RNAi- and Heterochromatin-Dependent Gene Silencing. Cell, 125, 873-886.
http://dx.doi.org/10.1016/j.cell.2006.04.025

[14]   Kozomara, A. and Griffiths-Jones, S. (2014) miRBase: Annotating High Confidence microRNAs Using Deep Sequencing Data. Nucleic Acids Research, 42, D68-D73.
http://dx.doi.org/10.1093/nar/gkt1181

[15]   Sun, G. and Gerecht, S. (2009) Vascular Regeneration: Engineering the Stem Cell Microenvironment. Regenerative Medicine, 4, 435-447.
http://dx.doi.org/10.2217/rme.09.1

[16]   Yang, Z. and Wu, J. (2007) MicroRNAs and Regenerative Medicine. DNA and Cell Biology, 26, 257-264.
http://dx.doi.org/10.1089/dna.2006.0548

[17]   Isner, J.M. and Asahara, T. (1999) Angiogenesis and Vasculo-genesis as Therapeutic Strategies for Postnatal Neovascularization. Journal of Clinical Investigation, 103, 1231-1236.
http://dx.doi.org/10.1172/JCI6889

[18]   Zhang, L. and Xu, Q. (2014) Stem/Progenitor Cells in Vascular Regeneration. Arteriosclerosis, Thrombosis, and Vascular Biology, 34, 1114-1119.
http://dx.doi.org/10.1161/ATVBAHA.114.303809

[19]   Guiducci, S., Distler, O., Distler, J.H. and Matucci-Cerinic, M. (2008) Mechanisms of Vascular Damage in SSc— Implications for Vascular Treatment Strategies. Rheumatology (Oxford), 47, v18-v20.
http://dx.doi.org/10.1093/rheumatology/ken267

[20]   Ang, Y.S., Tsai, S.Y., Lee, D.F., Monk, J., Su, J., Ratnakumar, K., Ding, J., Ge, Y., Darr, H., Chang, B., Wang, J., Rendl, M., Bernstein, E., Schaniel, C. and Lemischka, I.R. (2011) Wdr5 Mediates Self-Renewal and Reprogramming via the Embryonic Stem Cell Core Transcriptional Network. Cell, 145, 183-197.
http://dx.doi.org/10.1016/j.cell.2011.03.003

[21]   Bar-Nur, O., Russ, H.A., Efrat, S. and Benvenisty, N. (2011) Epigenetic Memory and Preferential Lineage-Specific Differentiation in Induced Pluripotent Stem Cells Derived from Human Pancreatic Islet Beta Cells. Cell Stem Cell, 9, 17-23.
http://dx.doi.org/10.1016/j.stem.2011.06.007

[22]   Hirai, H., Tani, T., Katoku-Kikyo, N., Kellner, S., Karian, P., Firpo, M. and Kikyo, N. (2011) Radical Acceleration of Nuclear Reprogramming by Chromatin Remodeling with the Transactivation Domain of MyoD. Stem Cells, 29, 1349-1361.
http://dx.doi.org/10.1002/stem.684

[23]   Wang, S. and Olson, E.N. (2009) AngiomiRs—Key Regulators of Angiogenesis. Current Opinion in Genetics & Development, 19, 205-211.
http://dx.doi.org/10.1016/j.gde.2009.04.002

[24]   Yang, W.J., Yang, D.D., Na, S., Sandusky, G.E., Zhang, Q. and Zhao, G. (2005) Dicer Is Required for Embryonic Angiogenesis during Mouse Development. The Journal of Biological Chemistry, 280, 9330-9335.
http://dx.doi.org/10.1074/jbc.M413394200

[25]   Suárez, Y., Fernandez-Hernando, C., Pober, J.S. and Sessa, W.C. (2007) Dicer Dependent microRNAs Regulate Gene Expression and Functions in Human Endothelial Cells. Circulation Research, 100, 1164-1173.
http://dx.doi.org/10.1161/01.RES.0000265065.26744.17

[26]   Kuehbacher, A., Urbich, C., Zeiher, A.M. and Dimmeler, S. (2007) Role of Dicer and Drosha for Endothelial microRNA Expression and Angiogenesis. Circulation Research, 101, 59-68.
http://dx.doi.org/10.1161/CIRCRESAHA.107.153916

[27]   Suárez, Y., Fernandez-Hernando, C., Yu, J., Gerber, S.A., Harrison, K.D., Pober, J.S., Iruela-Arispe, M.L., Merkenschlager, M. and Sessa, W.C. (2008) Dicer-Dependent Endothelial microRNAs Are Necessary for Postnatal Angiogenesis. Proceedings of the National Academy of Sciences of the United States of America, 105, 14082-14087.
http://dx.doi.org/10.1073/pnas.0804597105

[28]   Wang, S., Aurora, A.B., Johnson, B.A., Qi, X., McAnally, J., Hill, J.A., Richardson, J.A., Bassel-Duby, R. and Olson, E.N. (2008) The Endothelial-Specific microRNA miR-126 Governs Vascular Integrity and Angiogenesis. Developmental Cell, 15, 261-271.
http://dx.doi.org/10.1016/j.devcel.2008.07.002

[29]   Fish, J.E., Santoro, M.M., Morton, S.U., Yu, S., Yeh, R.F., Wythe, J.D., Ivey, K.N., Bruneau, B.G., Stainier, D.Y. and Srivastava, D. (2008) miR-126 Regulates Angiogenic Signaling and Vascular Integrity. Developmental Cell, 15, 272- 284.
http://dx.doi.org/10.1016/j.devcel.2008.07.008

[30]   Santulli, G., Wronska, A., Uryu, K., Diacovo, T.G., Gao, M., Marx, S.O., Kitajewski, J., Chilton, J.M., Akat, K.M., Tuschl, T., Marks, A.R. and Totary-Jain, H. (2014) A Selective microRNA-Based Strategy Inhibits Restenosis While Preserving Endothelial Function. Journal of Clinical Investigation, 124, 4102-4114.
http://dx.doi.org/10.1172/JCI76069

[31]   Yan, T., Cui, K., Huang, X., Ding, S., Zheng, Y., Luo, Q., Liu, X. and Zou, L. (2014) Assessment of Therapeutic Efficacy of miR-126 with Contrast-Enhanced Ultrasound in Preeclampsia Rats. Placenta, 35, 23-29.
http://dx.doi.org/10.1016/j.placenta.2013.10.017

[32]   Sessa, R., Seano, G., di Blasio, L., Gagliardi, P.A., Isella, C., Medico, E., Cotelli, F., Bussolino, F. and Primo, L. (2012) The miR-126 Regulates Angiopoietin-1 Signaling and Vessel Maturation by Targeting p85β. Biochimica et Biophysica Acta, 1823, 1925-1935.
http://dx.doi.org/10.1016/j.bbamcr.2012.07.011

[33]   Mogilyansky, E. and Rigoutsos, I. (2013) The miR-17/92 Cluster: A Comprehensive Update on Its Genomics, Genetics, Functions and Increasingly Important and Numerous Roles in Health and Disease. Cell Death & Differentiation, 20, 1603-1614.
http://dx.doi.org/10.1038/cdd.2013.125

[34]   Mendell, J.T. (2008) miRiad Roles for the miR-17-92 Cluster in Development and Disease. Cell, 133, 217-222.
http://dx.doi.org/10.1016/j.cell.2008.04.001

[35]   Dews, M., Homayouni, A., Yu, D., Murphy, D., Sevignani, C., Wentzel, E., Furth, E.E., Lee, W.M., Enders, G.H., Mendell, J.T. and Thomas-Tikhonenko, A. (2006) Augmentation of Tumor Angiogenesis by a Myc-Activated microRNA Cluster. Nature Genetics, 38, 1060-1065.
http://dx.doi.org/10.1038/ng1855

[36]   Doebele, C., Bonauer, A., Fischer, A., Scholz, A., Reiss, Y., Urbich, C., Hofmann, W.K., Zeiher, A.M. and Dimmeler, S. (2010) Members of the microRNA-17-92 Cluster Exhibit a Cell-Intrinsic Anti-angiogenic Function in Endothelial Cells. Blood, 115, 4944-4950.
http://dx.doi.org/10.1182/blood-2010-01-264812

[37]   Kaluza, D., Kroll, J., Gesierich, S., Manavski, Y., Boeckel, J.N., Doebele, C., Zelent, A., Rossig, L., Zeiher, A.M., Augustin, H.G., Urbich, C. and Dimmeler, S. (2013) Histone Deacetylase 9 Promotes Angiogenesis by Targeting the Antiangiogenic microRNA-17-92 Cluster in Endothelial Cells. Arteriosclerosis, Thrombosis, and Vascular Biology, 33, 533-543.
http://dx.doi.org/10.1161/ATVBAHA.112.300415

[38]   Yin, K.J., Olsen, K., Hamblin, M., Zhang, J., Schwendeman, S.P. and Chen, Y.E. (2012) Vascular Endothelial Cell- Specific microRNA-15a Inhibits Angiogenesis in Hindlimb Ischemia. The Journal of Biological Chemistry, 287, 27055-27064.
http://dx.doi.org/10.1074/jbc.M112.364414

[39]   Spinetti, G., Fortunato, O., Caporali, A., Shantikumar, S., Marchetti, M., Meloni, M., Descamps, B., Floris, I., Sangalli, E., Vono, R., Faglia, E., Specchia, C., Pintus, G., Madeddu, P. and Emanueli, C. (2013) MicroRNA-15a and microRNA-16 Impair Human Circulating Proangiogenic Cell Functions and Are Increased in the Proangiogenic Cells and Serum of Patients with Critical Limb Ischemia. Circulation Research, 112, 335-346.
http://dx.doi.org/10.1161/CIRCRESAHA.111.300418

[40]   Chen, Y. and Gorski, D.H. (2008) Regulation of Angiogenesis through a microRNA (miR-130a) That Down-Regulates Antiangiogenic Homeobox Genes GAX and HOXA5. Blood, 111, 1217-1226.
http://dx.doi.org/10.1182/blood-2007-07-104133

[41]   Richart, A., Loyer, X., Neri, T., Howangyin, K., Guerin, C.L., Ngkelo, A., Bakker, W., Zlatanova, I., Rouanet, M., Vilar, J., Levy, B., Rothenberg, M., Mallat, Z., Puceat, M. and Silvestre, J.S. (2014) MicroRNA-21 Coordinates Human Multipotent Cardiovascular Progenitors Therapeutic Potential. Stem Cells, 32, 2908-2922.
http://dx.doi.org/10.1002/stem.1789

[42]   Xu, X., Kriegel, A.J., Jiao, X., Liu, H., Bai, X., Olson, J., Liang, M. and Ding, X. (2014) miR-21 in Ischemia/Reperfusion Injury: A Double-Edged Sword? Physiological Genomics, 46, 789-797.
http://dx.doi.org/10.1152/physiolgenomics.00020.2014

[43]   Schaper, W. (2009) Collateral Circulation: Past and Present. Basic Research in Cardiology, 104, 5-21.
http://dx.doi.org/10.1007/s00395-008-0760-x

[44]   Hans, F.P., Moser, M., Bode, C. and Grundmann, S. (2010) MicroRNA Regulation of Angiogenesis and Arteriogenesis. Trends in Cardiovascular Medicine, 20, 253-262.
http://dx.doi.org/10.1016/j.tcm.2011.12.001

[45]   Weber, M., Baker, M.B., Moore, J.P. and Searles, C.D. (2010) MiR-21 Is Induced in Endothelial Cells by Shear Stress and Modulates Apoptosis and eNOS Activity. Biochemical and Bi-ophysical Research Communications, 393, 643-648.
http://dx.doi.org/10.1016/j.bbrc.2010.02.045

[46]   Ji, R., Cheng, Y., Yue, J., Yang, J., Liu, X., Chen, H., Dean, D.B. and Zhang, C. (2007) MicroRNA Expression Signature and Anti-sense-Mediated Depletion Reveal an Essential Role of MicroRNA in Vascular Neointimal Lesion Formation. Circulation Research, 100, 1579-1588.
http://dx.doi.org/10.1161/CIRCRESAHA.106.141986

[47]   Meng, F., Henson, R., Wehbe-Janek, H., Ghoshal, K., Jacob, S.T. and Patel, T. (2007) MicroRNA-21 Regulates Expression of the PTEN Tumor Suppressor Gene in Human Hepatocellular Cancer. Gastroenterology, 133, 647-658.
http://dx.doi.org/10.1053/j.gastro.2007.05.022

[48]   Hutcheson, R., Chaplin, J., Hutcheson, B., Borthwick, F., Proctor, S., Gebb, S., Jadhav, R., Smith, E., Russell, J.C. and Rocic, P. (2014) miR-21 Normalizes Vascular Smooth Muscle Proliferation and Improves Coronary Collateral Growth in Metabolic Syndrome. The FASEB Journal, 28, 4088-4099.
http://dx.doi.org/10.1096/fj.14-251223

[49]   Landskroner-Eiger, S., Qiu, C., Perrotta, P., Siragusa, M., Lee, M.Y., Ul-rich, V., Luciano, A.K., Zhuang, Z.W., Corti, F., Simons, M., Montgomery, R.L., Wu, D., Yu, J. and Sessa, W.C. (2015) Endothelial miR-17 Approximately 92 Cluster Negatively Regulates Arteriogenesis via miRNA-19 Repression of WNT Signaling. Proceedings of the National Academy of Sciences of the United States of America, 112, 12812-12817.
http://dx.doi.org/10.1073/pnas.1507094112

[50]   Pankratz, F., Bemtgen, X., Zeiser, R., Leonhardt, F., Kreuzaler, S., Hilgendorf, I., Smolka, C., Helbing, T., Hoefer, I., Esser, J.S., Kustermann, M., Moser, M., Bode, C. and Grundmann, S. (2015) MicroRNA-155 Exerts Cell-Specific Antiangiogenic but Proarteriogenic Effects during Adaptive Neovascularization. Circulation, 131, 1575-1589.
http://dx.doi.org/10.1161/CIRCULATIONAHA.114.014579

[51]   Eisenhardt, S.U., Weiss, J.B., Smolka, C., Maxeiner, J., Pankratz, F., Bemtgen, X., Kustermann, M., Thiele, J.R., Schmidt, Y., Bjoern Stark, G., Moser, M., Bode, C. and Grundmann, S. (2015) MicroRNA-155 Aggravates Ischemia- Reperfusion Injury by Modulation of Inflammatory Cell Recruitment and the Respiratory Oxidative Burst. Basic Research in Cardiology, 110, 32.
http://dx.doi.org/10.1007/s00395-015-0490-9

[52]   Grundmann, S., Hans, F.P., Kinniry, S., Heinke, J., Helbing, T., Bluhm, F., Sluijter, J.P., Hoefer, I., Pasterkamp, G., Bode, C. and Moser, M. (2011) MicroRNA-100 Regulates Neovascular-ization by Suppression of Mammalian Target of Rapamycin in Endothelial and Vascular Smooth Muscle Cells. Circulation, 123, 999-1009.
http://dx.doi.org/10.1161/CIRCULATIONAHA.110.000323

[53]   Leonhardt, F., Grundmann, S., Behe, M., Bluhm, F., Dumont, R.A., Braun, F., Fani, M., Riesner, K., Prinz, G., Hechinger, A.K., Gerlach, U.V., Dierbach, H., Penack, O., Schmitt-Graff, A., Finke, J., Weber, W.A. and Zeiser, R. (2013) Inflammatory Neovascularization during Graft-versus-Host Disease Is Regulated by Alphav Integrin and miR-100. Blood, 121, 3307-3318.
http://dx.doi.org/10.1182/blood-2012-07-442665

[54]   Welten, S.M., Bastiaansen, A.J., de Jong, R.C., de Vries, M.R., Peters, E.A., Boonstra, M.C., Sheikh, S.P., La Monica, N., Kandimalla, E.R., Quax, P.H. and Nossent, A.Y. (2014) Inhibition of 14q32 MicroRNAs miR-329, miR-487b, miR-494, and miR-495 Increases Neovascularization and Blood Flow Recovery after Ischemia. Circulation Research, 115, 696-708.
http://dx.doi.org/10.1161/CIRCRESAHA.114.304747

[55]   Lei, Z., van Mil, A., Brandt, M.M., Grundmann, S., Hoefer, I., Smits, M., El Azzouzi, H., Fukao, T., Cheng, C., Doevendans, P.A. and Sluijter, J.P. (2015) MicroRNA-132/212 Family Enhances Arteriogenesis after Hindlimb Ischaemia through Modulation of the Ras-MAPK Pathway. Journal of Cellular and Molecular Medicine, 19, 1994-2005.
http://dx.doi.org/10.1111/jcmm.12586

[56]   Asahara, T., Murohara, T., Sullivan, A., Silver, M., van der Zee, R., Li, T., Witzenbichler, B., Schatteman, G. and Isner, J.M. (1997) Isolation of Putative Progenitor Endothelial Cells for Angiogenesis. Science, 275, 964-967.
http://dx.doi.org/10.1126/science.275.5302.964

[57]   Minami, Y., Satoh, M., Maesawa, C., Takahashi, Y., Tabuchi, T., Itoh, T. and Nakamura, M. (2009) Effect of Atorvastatin on microRNA 221/222 Expression in Endothelial Progenitor Cells Obtained from Patients with Coronary Artery Disease. European Journal of Clinical Investigation, 39, 359-367.
http://dx.doi.org/10.1111/j.1365-2362.2009.02110.x

[58]   Chang, T.Y., Huang, T.S., Wang, H.W., Chang, S.J., Lo, H.H., Chiu, Y.L., Wang, Y.L., Hsiao, C.D., Tsai, C.H., Chan, C.H., You, R.I., Wu, C.H., Tsai, T.N., Cheng, S.M. and Cheng, C.C. (2014) miRNome Traits Analysis on Endothelial Lineage Cells Discloses Biomarker Potential Circulating microRNAs Which Affect Progenitor Activities. BMC Genomics, 15, 802.
http://dx.doi.org/10.1186/1471-2164-15-802

[59]   Zhang, X., Mao, H., Chen, J.Y., Wen, S., Li, D., Ye, M. and Lv, Z. (2013) Increased Expression of microRNA-221 Inhibits PAK1 in Endothelial Progenitor Cells and Impairs Its Function via c-Raf/MEK/ERK Pathway. Biochemical and Biophysical Research Communications, 431, 404-408.
http://dx.doi.org/10.1016/j.bbrc.2012.12.157

[60]   Zuo, K., Li, M., Zhang, X., Lu, C., Wang, S., Zhi, K. and He, B. (2015) MiR-21 Suppresses Endothelial Progenitor Cell Proliferation by Activating the TGFbeta Signaling Pathway via Down-Regulation of WWP1. International Journal of Clinical and Experimental Pathology, 8, 414-422.

[61]   Meng, S., Cao, J.T., Zhang, B., Zhou, Q., Shen, C.X. and Wang, C.Q. (2012) Down-Regulation of microRNA-126 in Endothelial Progenitor Cells from Diabetes Patients, Impairs Their Functional Properties, via Target Gene Spred-1. Journal of Molecular and Cellular Cardiology, 53, 64-72.
http://dx.doi.org/10.1016/j.yjmcc.2012.04.003

[62]   Ye, M., Li, D., Yang, J., Xie, J., Yu, F., Ma, Y., Zhu, X., Zhao, J. and Lv, Z. (2015) MicroRNA-130a Targets MAP3K12 to Modulate Diabetic Endothelial Progenitor Cell Function. Cellular Physiology and Biochemistry, 36, 712- 726.
http://dx.doi.org/10.1159/000430132

[63]   Tabuchi, T., Satoh, M., Itoh, T. and Nakamura, M. (2012) MicroRNA-34a Regulates the Longevity-Associated Protein SIRT1 in Coronary Artery Disease: Effect of Statins on SIRT1 and microRNA-34a Expression. Clinical Science, 123, 161-171.
http://dx.doi.org/10.1042/CS20110563

[64]   Zhao, T., Li, J. and Chen, A.F. (2010) MicroRNA-34a Induces Endothelial Progenitor Cell Senescence and Impedes Its Angiogenesis via Suppressing Silent Information Regulator 1. American Journal of Physiology—Endocrinology and Metabolism, 299, E110-E116.
http://dx.doi.org/10.1152/ajpendo.00192.2010

[65]   Zhu, S., Deng, S., Ma, Q., Zhang, T., Jia, C., Zhuo, D., Yang, F., Wei, J., Wang, L., Dykxhoorn, D.M., Hare, J.M., Goldschmidt-Clermont, P.J. and Dong, C. (2013) MicroRNA-10A* and MicroRNA-21 Modulate Endothelial Progenitor Cell Senescence via Suppressing High-Mobility Group A2. Circulation Research, 112, 152-164.
http://dx.doi.org/10.1161/CIRCRESAHA.112.280016

[66]   Zheng, Y. and Xu, Z. (2014) MicroRNA-22 Induces Endothelial Progenitor Cell Senescence by Targeting AKT3. Cellular Physiology and Biochemistry, 34, 1547-1555.
http://dx.doi.org/10.1159/000366358

[67]   Boyette, L.B., Creasey, O.A., Guzik, L., Lozito, T. and Tuan, R.S. (2014) Human Bone Marrow-Derived Mesenchymal Stem Cells Display Enhanced Clonogenicity but Impaired Differentiation with Hypoxic Preconditioning. Stem Cells Translational Medicine, 3, 241-254.
http://dx.doi.org/10.5966/sctm.2013-0079

[68]   Meng, S., Cao, J., Wang, L., Zhou, Q., Li, Y., Shen, C., Zhang, X. and Wang, C. (2012) MicroRNA 107 Partly Inhibits Endothelial Progenitor Cells Differentiation via HIF-1beta. PLoS ONE, 7, e40323.
http://dx.doi.org/10.1371/journal.pone.0040323

[69]   Goretti, E., Rolland-Turner, M., Leonard, F., Zhang, L., Wagner, D.R. and Devaux, Y. (2013) MicroRNA-16 Affects Key Functions of Human Endothelial Progenitor Cells. Journal of Leukocyte Biology, 93, 645-655.
http://dx.doi.org/10.1189/jlb.1012511

[70]   Obi, S., Yamamoto, K. and Ando, J. (2014) Effects of Shear Stress on Endothelial Progenitor Cells. Journal of Biomedical Nanotechnology, 10, 2586-2597.
http://dx.doi.org/10.1166/jbn.2014.2014

[71]   Cheng, B.B., Qu, M.J., Wu, L.L., Shen, Y., Yan, Z.Q., Zhang, P., Qi, Y.X. and Jiang, Z.L. (2014) MicroRNA-34a Targets Forkhead Box j2 to Modulate Differentiation of Endothelial Progenitor Cells in Response to Shear Stress. Journal of Molecular and Cellular Cardiology, 74, 4-12.
http://dx.doi.org/10.1016/j.yjmcc.2014.04.016

[72]   Qiang, L., Hong, L., Ningfu, W., Huaihong, C. and Jing, W. (2013) Expression of miR-126 and miR-508-5p in Endothelial Progenitor Cells Is Associated with the Prognosis of Chronic Heart Failure Patients. International Journal of Cardiology, 168, 2082-2088.
http://dx.doi.org/10.1016/j.ijcard.2013.01.160

[73]   Goerke, S.M., Kiefer, L.S., Stark, G.B., Simunovic, F. and Finkenzeller, G. (2015) miR-126 Modulates Angiogenic Growth Parameters of Peripheral Blood Endothelial Progenitor Cells. The Journal of Biological Chemistry, 396, 245-252.
http://dx.doi.org/10.1515/hsz-2014-0259

[74]   Meng, Q., Wang, W., Yu, X., Li, W., Kong, L., Qian, A., Li, C. and Li, X. (2015) Upregulation of MicroRNA-126 Contributes to Endothelial Progenitor Cell Function in Deep Vein Thrombosis via Its Target PIK3R2. Journal of Cellular Biochemistry, 116, 1613-1623.
http://dx.doi.org/10.1002/jcb.25115

[75]   Thomson, J.A., Itskovitz-Eldor, J., Shapiro, S.S., Waknitz, M.A., Swiergiel, J.J., Marshall, V.S. and Jones, J.M. (1998) Embryonic Stem Cell Lines Derived from Human Blastocysts. Science, 282, 1145-1147.
http://dx.doi.org/10.1126/science.282.5391.1145

[76]   Houbaviy, H.B., Murray, M.F. and Sharp, P.A. (2003) Embryonic Stem Cell-Specific MicroRNAs. Developmental Cell, 5, 351-358.
http://dx.doi.org/10.1016/S1534-5807(03)00227-2

[77]   Gruber, A.J., Grandy, W.A., Balwierz, P.J., Dimitrova, Y.A., Pachkov, M., Ciaudo, C., Nimwegen, E. and Zavolan, M. (2014) Embryonic Stem Cell-Specific microRNAs Contribute to Pluripotency by Inhibiting Regulators of Multiple Differentiation Pathways. Nucleic Acids Research, 42, 9313-9326.
http://dx.doi.org/10.1093/nar/gku544

[78]   Kanellopoulou, C., Muljo, S.A., Kung, A.L., Ganesan, S., Drapkin, R., Jenuwein, T., Livingston, D.M. and Rajewsky, K. (2005) Dicer-Deficient Mouse Embryonic Stem Cells Are Defective in Differentiation and Centromeric Silencing. Genes & Development, 19, 489-501.
http://dx.doi.org/10.1101/gad.1248505

[79]   Judson, R.L., Babiarz, J.E., Venere, M. and Blelloch, R. (2009) Embryonic Stem Cell-Specific microRNAs Promote Induced Pluripotency. Nature Biotechnology, 27, 459-461.
http://dx.doi.org/10.1038/nbt.1535

[80]   Stadler, B., Ivanovska, I., Mehta, K., Song, S., Nelson, A., Tan, Y., Mathieu, J., Darby, C., Blau, C.A., Ware, C., Peters, G., Miller, D.G., Shen, L., Cleary, M.A. and Ruohola-Baker, H. (2010) Characteri-zation of microRNAs Involved in Embryonic Stem Cell States. Stem Cells and Development, 19, 935-950.
http://dx.doi.org/10.1089/scd.2009.0426

[81]   Jia, W., Chen, W. and Kang, J. (2013) The Functions of microRNAs and Long Non-Coding RNAs in Embryonic and Induced Pluripotent Stem Cells. Genomics Proteomics Bioinformatics, 11, 275-283.
http://dx.doi.org/10.1016/j.gpb.2013.09.004

[82]   Card, D.A., Hebbar, P.B., Li, L., Trotter, K.W., Komatsu, Y., Mishina, Y. and Archer, T.K. (2008) Oct4/Sox2-Regulated miR-302 Targets Cyclin D1 in Human Embryonic Stem Cells. Molecular and Cellular Biology, 28, 6426-6438.
http://dx.doi.org/10.1128/MCB.00359-08

[83]   Anokye-Danso, F., Trivedi, C.M., Juhr, D., Gupta, M., Cui, Z., Tian, Y., Zhang, Y., Yang, W., Gruber, P.J., Epstein, J.A. and Morrisey, E.E. (2011) Highly Efficient miRNA-Mediated Reprogramming of Mouse and Human Somatic Cells to Pluripotency. Cell Stem Cell, 8, 376-388.
http://dx.doi.org/10.1016/j.stem.2011.03.001

[84]   Li, M.A. and He, L. (2012) microRNAs as Novel Regulators of Stem Cell Pluripotency and Somatic Cell Reprogramming. Bioessays, 34, 670-680.
http://dx.doi.org/10.1002/bies.201200019

[85]   Tay, Y., Zhang, J., Thomson, A.M., Lim, B. and Rigoutsos, I. (2008) MicroRNAs to Nanog, Oct4 and Sox2 Coding Regions Modulate Embryonic Stem Cell Differentiation. Nature, 455, 1124-1128.
http://dx.doi.org/10.1038/nature07299

[86]   Singh, S.K., Kagalwala, M.N., Parker-Thornburg, J., Adams, H. and Majumder, S. (2008) REST Maintains Self- Renewal and Pluripotency of Embryonic Stem Cells. Nature, 453, 223-227.
http://dx.doi.org/10.1038/nature06863

[87]   Xu, N., Papagiannakopoulos, T., Pan, G., Thomson, J.A. and Kosik, K.S. (2009) MicroRNA-145 Regulates OCT4, SOX2, and KLF4 and Represses Pluripotency in Human Embryonic Stem Cells. Cell, 137, 647-658.
http://dx.doi.org/10.1016/j.cell.2009.02.038

[88]   Yoo, J.K., Kim, J., Choi, S.J., Noh, H.M., Kwon, Y.D., Yoo, H., Yi, H.S., Chung, H.M. and Kim, J.K. (2012) Discovery and Characterization of Novel microRNAs during Endothelial Differentiation of Human Embryonic Stem Cells. Stem Cells and Development, 21, 2049-2057.
http://dx.doi.org/10.1089/scd.2011.0500

[89]   Kane, N.M., Howard, L., Descamps, B., Meloni, M., McClure, J., Lu, R., McCahill, A., Breen, C., Mackenzie, R.M., Delles, C., Mountford, J.C., Milligan, G., Emanueli, C. and Baker, A.H. (2012) Role of microRNAs 99b, 181a, and 181b in the Differentiation of Human Embryonic Stem Cells to Vascular Endothelial Cells. Stem Cells, 30, 643-654.
http://dx.doi.org/10.1002/stem.1026

[90]   Wang, L., Su, W., Du, W., Xu, Y., Wang, L., Kong, D., Han, Z., Zheng, G. and Li, Z. (2015) Gene and MicroRNA Profiling of Human Induced Pluripotent Stem Cell-Derived Endothelial Cells. Stem Cell Reviews and Reports, 11, 219- 227.
http://dx.doi.org/10.1007/s12015-014-9582-4

[91]   Treguer, K., Heinrich, E.M., Ohtani, K., Bonauer, A. and Dimmeler, S. (2012) Role of the microRNA-17-92 Cluster in the Endothelial Differentiation of Stem Cells. Journal of Vascular Research, 49, 447-460.
http://dx.doi.org/10.1159/000339429

[92]   Luo, Z., Wen, G., Wang, G., Pu, X., Ye, S., Xu, Q., Wang, W. and Xiao, Q. (2013) MicroRNA-200C and -150 Play an Important Role in Endothelial Cell Differentiation and Vasculogenesis by Targeting Transcription Repressor ZEB1. Stem Cells, 31, 1749-1762.
http://dx.doi.org/10.1002/stem.1448

[93]   Gill, J.G., Langer, E.M., Lindsley, R.C., Cai, M., Murphy, T.L. and Murphy, K.M. (2012) Snail Promotes the Cell-Autonomous Generation of Flk1+ Endothelial Cells through the Repression of the microRNA-200 Family. Stem Cells and Development, 21, 167-176.
http://dx.doi.org/10.1089/scd.2011.0194

[94]   Shi, X., Richard, J., Zirbes, K.M., Gong, W., Lin, G., Kyba, M., Thomson, J.A., Koyano-Nakagawa, N. and Garry, D.J. (2014) Cooperative Interaction of Etv2 and Gata2 Regulates the Development of Endothelial and Hematopoietic Lineages. Developmental Biology, 389, 208-218.
http://dx.doi.org/10.1016/j.ydbio.2014.02.018

[95]   Moore, J.C., Sheppard-Tindell, S., Shestopalov, I.A., Yamazoe, S., Chen, J.K. and Lawson, N.D. (2013) Post- Transcriptional Mechanisms Contribute to Etv2 Repression during Vascular Development. Developmental Biology, 384, 128-140.
http://dx.doi.org/10.1016/j.ydbio.2013.08.028

[96]   Fiedler, J., Jazbutyte, V., Kirchmaier, B.C., Gupta, S.K., Lorenzen, J., Hartmann, D., Galuppo, P., Kneitz, S., Pena, J.T., Sohn-Lee, C., Loyer, X., Soutschek, J., Brand, T., Tuschl, T., Heineke, J., Martin, U., Schulte-Merker, S., Ertl, G., Engelhardt, S., Bauersachs, J. and Thum, T. (2011) MicroRNA-24 Regulates Vascularity after Myocardial Infarction. Circulation, 124, 720-730.
http://dx.doi.org/10.1161/CIRCULATIONAHA.111.039008

[97]   Robinton, D.A. and Daley, G.Q. (2012) The Promise of Induced Pluripotent Stem Cells in Research and Therapy. Nature, 481, 295-305.
http://dx.doi.org/10.1038/nature10761

[98]   Takahashi, K. and Yamanaka, S. (2006) Induction of Pluripotent Stem Cells from Mouse Embryonic and Adult Fibroblast Cultures by Defined Factors. Cell, 126, 663-676.
http://dx.doi.org/10.1016/j.cell.2006.07.024

[99]   Yu, J., Vodyanik, M.A., Smuga-Otto, K., Antosiewicz-Bourget, J., Frane, J.L., Tian, S., Nie, J., Jonsdottir, G.A., Ruotti, V., Stewart, R., Slukvin, I.I. and Thomson, J.A. (2007) Induced Plu-ripotent Stem Cell Lines Derived from Human Somatic Cells. Science, 318, 1917-1920.
http://dx.doi.org/10.1126/science.1151526

[100]   Wang, Y., Baskerville, S., Shenoy, A., Babiarz, J.E., Baehner, L. and Blelloch, R. (2008) Embryonic Stem Cell-Specific microRNAs Regulate the G1-S Transition and Promote Rapid Proliferation. Nature Genetics, 40, 1478-1483.
http://dx.doi.org/10.1038/ng.250

[101]   Li, Z., Yang, C.S., Nakashima, K. and Rana, T.M. (2011) Small RNA-Mediated Regulation of iPS Cell Generation. The EMBO Journal, 30, 823-834.
http://dx.doi.org/10.1038/emboj.2011.2

[102]   Subramanyam, D., Lamouille, S., Judson, R.L., Liu, J.Y., Bucay, N., Derynck, R. and Blelloch, R. (2011) Multiple Targets of miR-302 and miR-372 Promote Reprogramming of Human Fibroblasts to Induced Pluripotent Stem Cells. Nature Biotechnology, 29, 443-448.
http://dx.doi.org/10.1038/nbt.1862

[103]   Deng, W., Cao, X., Chen, J., Zhang, Z., Yu, Q., Wang, Y., Shao, G., Zhou, J., Gao, X., Yu, J. and Xu, X. (2015) MicroRNA Replacing Oncogenic Klf4 and c-Myc for Generating iPS Cells via Cationized Pleurotus eryngii Polysaccharide-Based Nanotransfection. ACS Applied Materials & Interfaces, 7, 18957-18966.
http://dx.doi.org/10.1021/acsami.5b06768

[104]   Zhang, Z., Xiang, D., Heriyanto, F., Gao, Y., Qian, Z. and Wu, W.S. (2013) Dissecting the Roles of miR-302/367 Cluster in Cellular Reprogramming Using TALE-Based Repressor and TALEN. Stem Cell Reports, 1, 218-225.
http://dx.doi.org/10.1016/j.stemcr.2013.07.002

[105]   Lin, S.L., Chang, D.C., Lin, C.H., Ying, S.Y., Leu, D. and Wu, D.T. (2011) Regulation of Somatic Cell Reprogramming through Inducible mir-302 Expression. Nucleic Acids Research, 39, 1054-1065.
http://dx.doi.org/10.1093/nar/gkq850

[106]   Yang, C.S., Li, Z. and Rana, T.M. (2011) microRNAs Modulate iPS Cell Generation. RNA, 17, 1451-1460.
http://dx.doi.org/10.1261/rna.2664111

[107]   Choi, Y.J., Lin, C.P., Ho, J.J., He, X., Okada, N., Bu, P., Zhong, Y., Kim, S.Y., Bennett, M.J., Chen, C., Ozturk, A., Hicks, G.G., Hannon, G.J. and He, L. (2011) miR-34 miRNAs Provide a Barrier for Somatic Cell Reprogramming. Nature Cell Biology, 13, 1353-1360.
http://dx.doi.org/10.1038/ncb2366

[108]   Di Bernardini, E., Campagnolo, P., Margariti, A., Zampetaki, A., Karamariti, E., Hu, Y. and Xu, Q. (2014) Endothelial Lineage Differentiation from Induced Pluripotent Stem Cells Is Regulated by microRNA-21 and Transforming Growth Factor beta2 (TGF-beta2) Pathways. The Journal of Biological Chemistry, 289, 3383-3393.
http://dx.doi.org/10.1074/jbc.M113.495531

[109]   Li, Z., Margariti, A., Wu, Y., Yang, F., Hu, J., Zhang, L. and Chen, T. (2015) MicroRNA-199a Induces Differentiation of Induced Pluripotent Stem Cells into Endothelial Cells by Targeting Sirtuin 1. Molecular Medicine Reports, 12, 3711-3717.

[110]   Chen, T., Margariti, A., Kelaini, S., Cochrane, A., Guha, S.T., Hu, Y., Stitt, A.W., Zhang, L. and Xu, Q. (2015) MicroRNA-199b Modulates Vascular Cell Fate during iPS Cell Differentiation by Targeting the Notch Ligand Jagged1 and Enhancing VEGF Signaling. Stem Cells, 33, 1405-1418.
http://dx.doi.org/10.1002/stem.1930

 
 
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