Advertisement

Stem Cell Reviews and Reports

, Volume 11, Issue 2, pp 219–227 | Cite as

Gene and MicroRNA Profiling of Human Induced Pluripotent Stem Cell-Derived Endothelial Cells

  • Lina Wang
  • Weijun Su
  • Wei Du
  • Yang Xu
  • Lijun Wang
  • Deling Kong
  • Zhongchao Han
  • Guoguang Zheng
  • Zongjin LiEmail author
Article

Abstract

Introduction

The differentiated cell lineages from human embryonic stem cells (hESCs) and human induced pluripotent stem cells (hiPSCs) have shown their potential in regenerative medicine. However, the functional and transcriptional microRNA (miRNA) expression pattern during endothelial differentiation has yet to be characterized.

Methods

In this study, hESCs and hiPSCs were differentiated into endothelial cells (ECs). Then the endothelial-related gene profiling and miRNA profiling of hiPSCs, hESCs, hiPSCs derived endothelial cells (hiPSC-ECs), hESC derived endothelial cells (hESC-ECs) and human umbilical vein endothelial cells (HUVECs) were compared using RT-PCR Array. The data was analyzed using the data analysis system on QIAGEN’s website.

Results

Our analysis demonstrated that the endothelial differentiation was triggered after EB formation and the EC-associated genes were up-regulated swiftly in both hESC-EBs and hiPSC-EBs; hiPSC-ECs and hESC-ECs had the similar EC-associated gene expression patterns. Moreover, we report here the first miRNA profiling study of hiPSC-ECs. Analyzing 376 unique miRNAs, we have identified several interesting miRNAs, including miR-20a, miR-20b, miR-222, miR-210, which have been previously reported to be involved in endothelial differentiation and show surprising expression patterns across our samples. We also identified novel miRNAs, such as miR-125a-5p, miR-149, miR-296-5p, miR-100, miR-27b, miR-181a and miR-137, which were up-regulated in both hiPSC-ECs and hESC-ECs during endothelial differentiation.

Conclusion

hiPSC-ECs and hESC-ECs exhibited a high degree of similarity with HUVECs in EC-associated genes expression. And the miRNA profiling analysis revealed significant differences between hiPSCs and hESCs, but a high degree of similarity between hiPSC-ECs and hESC-ECs.

Keywords

Human induced pluripotent stem cells (hiPSCs) Human embryonic stem cells (hESCs) Endothelial cells Differentiation Gene profiling MicroRNAs 

Notes

Acknowledgments

This work was partially supported by grants from the National Natural Science Foundation of China (81320108014, 81371620, 81300376), National Basic Research Program of China (2011CB964903), PUMC Youth Fund and the Fundamental Research Funds for the Central Universities (33320140141), Tianjin Natural Science Foundation (12JCZDJC24900, 14JCQNJC10600) and Program for Changjiang Scholars and Innovative Research Team in University (IRT13023).

Competing Interests

None

Contribution

ZL was the principal investigator and took primary responsibility for the paper. ZL, DK, GZ and ZH conceived and designed the experiments. LinaW, WS, WD, YX and LijunW performed the experiments. LinaW, WS and ZL analyzed the data. ZL and LinaW wrote the paper.

Supplementary material

12015_2014_9582_MOESM1_ESM.docx (41 kb)
ESM 1 (DOCX 41 kb)

References

  1. 1.
    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
  2. 2.
    Robinton, D. A., & Daley, G. Q. (2012). The promise of induced pluripotent stem cells in research and therapy. Nature, 481, 295–305.CrossRefPubMedCentralPubMedGoogle Scholar
  3. 3.
    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
  4. 4.
    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
  5. 5.
    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
  6. 6.
    Park, I. H., Zhao, R., West, J. A., et al. (2008). Reprogramming of human somatic cells to pluripotency with defined factors. Nature, 451, 141–146.CrossRefPubMedGoogle Scholar
  7. 7.
    Okita, K., Ichisaka, T., & Yamanaka, S. (2007). Generation of germline-competent induced pluripotent stem cells. Nature, 448, 313–317.CrossRefPubMedGoogle Scholar
  8. 8.
    Takahashi, K., Tanabe, K., Ohnuki, M., et al. (2007). Induction of pluripotent stem cells from adult human fibroblasts by defined factors. Cell, 131, 861–872.CrossRefPubMedGoogle Scholar
  9. 9.
    Nakagawa, M., Koyanagi, M., Tanabe, K., et al. (2008). Generation of induced pluripotent stem cells without Myc from mouse and human fibroblasts. Nature Biotechnology, 26, 101–106.CrossRefPubMedGoogle Scholar
  10. 10.
    Li, Z., Hu, S., Ghosh, Z., et al. (2011). Functional characterization and expression profiling of human induced pluripotent stem cell- and embryonic stem cell-derived endothelial cells. Stem Cells and Development, 20, 1701–1710.CrossRefPubMedCentralPubMedGoogle Scholar
  11. 11.
    Choi, K. D., Yu, J., Smuga-Otto, K., et al. (2009). Hematopoietic and endothelial differentiation of human induced pluripotent stem cells. Stem Cells, 27, 559–567.CrossRefPubMedCentralPubMedGoogle Scholar
  12. 12.
    Li, Z., Wilson, K. D., Smith, B., et al. (2009). Functional and transcriptional characterization of human embryonic stem cell-derived endothelial cells for treatment of myocardial infarction. PLoS One, 4, e8443.CrossRefPubMedCentralPubMedGoogle Scholar
  13. 13.
    Xie, C. Q., Huang, H., Wei, S., et al. (2009). A comparison of murine smooth muscle cells generated from embryonic versus induced pluripotent stem cells. Stem Cells and Development, 18, 741–748.CrossRefPubMedCentralPubMedGoogle Scholar
  14. 14.
    Zhang, J., Wilson, G. F., Soerens, A. G., et al. (2009). Functional cardiomyocytes derived from human induced pluripotent stem cells. Circulation Research, 104, e30–e41.CrossRefPubMedCentralPubMedGoogle Scholar
  15. 15.
    Leeper, N. J., Hunter, A. L., & Cooke, J. P. (2010). Stem cell therapy for vascular regeneration: adult, embryonic, and induced pluripotent stem cells. Circulation, 122, 517–526.CrossRefPubMedCentralPubMedGoogle Scholar
  16. 16.
    Li, Z., Suzuki, Y., Huang, M., et al. (2008). Comparison of reporter gene and iron particle labeling for tracking fate of human embryonic stem cells and differentiated endothelial cells in living subjects. Stem Cells, 26, 864–873.CrossRefPubMedCentralPubMedGoogle Scholar
  17. 17.
    Kane, N. M., Howard, L., Descamps, B., et al. (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.CrossRefPubMedCentralPubMedGoogle Scholar
  18. 18.
    Jozefczuk, J., Prigione, A., Chavez, L., et al. (2011). Comparative analysis of human embryonic stem cell and induced pluripotent stem cell-derived hepatocyte-like cells reveals current drawbacks and possible strategies for improved differentiation. Stem Cells and Development, 20, 1259–1275.CrossRefPubMedGoogle Scholar
  19. 19.
    Bock, C., Kiskinis, E., Verstappen, G., et al. (2011). Reference maps of human ES and iPS cell variation enable high-throughput characterization of pluripotent cell lines. Cell, 144, 439–452.CrossRefPubMedCentralPubMedGoogle Scholar
  20. 20.
    Kane, N. M., Meloni, M., Spencer, H. L., et al. (2010). Derivation of endothelial cells from human embryonic stem cells by directed differentiation: analysis of microRNA and angiogenesis in vitro and in vivo. Arteriosclerosis, Thrombosis, and Vascular Biology, 30, 1389–1397.CrossRefPubMedGoogle Scholar
  21. 21.
    Wilson, K. D., Venkatasubrahmanyam, S., Jia, F., et al. (2009). MicroRNA profiling of human-induced pluripotent stem cells. Stem Cells and Development, 18, 749–758.CrossRefPubMedCentralPubMedGoogle Scholar
  22. 22.
    Stadler, B., Ivanovska, I., Mehta, K., et al. (2010). Characterization of microRNAs involved in embryonic stem cell states. Stem Cells and Development, 19, 935–950.CrossRefPubMedCentralPubMedGoogle Scholar
  23. 23.
    Tiscornia, G., & Izpisua Belmonte, J. C. (2010). MicroRNAs in embryonic stem cell function and fate. Genes and Development, 24, 2732–2741.CrossRefPubMedCentralPubMedGoogle Scholar
  24. 24.
    Mallanna, S. K., & Rizzino, A. (2010). Emerging roles of microRNAs in the control of embryonic stem cells and the generation of induced pluripotent stem cells. Developmental Biology, 344, 16–25.CrossRefPubMedCentralPubMedGoogle Scholar
  25. 25.
    Wilson, K. D., Hu, S., Venkatasubrahmanyam, S., et al. (2010). Dynamic microRNA expression programs during cardiac differentiation of human embryonic stem cells: role for miR-499. Circulation. Cardiovascular Genetics, 3, 426–435.CrossRefPubMedCentralPubMedGoogle Scholar
  26. 26.
    Yoo, J. K., Kim, J., Choi, S. J., et al. (2012). Discovery and characterization of novel microRNAs during endothelial differentiation of human embryonic stem cells. Stem Cells and Development, 21, 2049–2057.CrossRefPubMedCentralPubMedGoogle Scholar
  27. 27.
    Kim, H., Lee, G., Ganat, Y., et al. (2011). miR-371-3 expression predicts neural differentiation propensity in human pluripotent stem cells. Cell Stem Cell, 8, 695–706.CrossRefPubMedGoogle Scholar
  28. 28.
    Palmieri, D., Capponi, S., Geroldi, A., et al. (2014). TNF a induces the expression of genes associated with endothelial dysfunction through p38MAPK-mediated down-regulation of miR-149. Biochemical And Biophysical Research Communications, 443, 246–251.CrossRefPubMedGoogle Scholar
  29. 29.
    Kazenwadel, J., Michael, M. Z., & Harvey, N. L. (2010). Prox1 expression is negatively regulated by miR-181 in endothelial cells Prox1 expression is negatively regulated by miR-181 in endothelial cells. Blood, 116, 2395–2401.CrossRefPubMedGoogle Scholar
  30. 30.
    Urbich, C., Kaluza, D., Frömel, T., et al. (2012). MicroRNA-27a / b controls endothelial cell repulsion and angiogenesis by targeting semaphorin 6A. Blood, 119, 1607–1616.CrossRefPubMedGoogle Scholar
  31. 31.
    Chamorro-Jorganes, A., Araldi, E., Rotllan, N., et al. (2014). Autoregulation of glypican-1 by intronic microRNA-149 fine tunes the angiogenic response to FGF2 in human endothelial cells. Journal of Cell Science, 127, 1169–1178.CrossRefPubMedCentralPubMedGoogle Scholar
  32. 32.
    Che, P., Liu, J., Shan, Z., et al. (2014). miR-125a-5p impairs endothelial cell angiogenesis in aging mice via RTEF-1 downregulation. Aging Cell, 13, 926–934.CrossRefPubMedCentralPubMedGoogle Scholar
  33. 33.
    Iaconetti, C., Gareri, C., Polimeni, A., et al. (2013). Non-coding RNAs: the “dark matter” of cardiovascular pathophysiology. International Journal of Molecular Sciences, 14, 19987–20018.CrossRefPubMedCentralPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2015

Authors and Affiliations

  • Lina Wang
    • 1
  • Weijun Su
    • 2
  • Wei Du
    • 2
  • Yang Xu
    • 2
  • Lijun Wang
    • 3
  • Deling Kong
    • 4
  • Zhongchao Han
    • 1
  • Guoguang Zheng
    • 1
  • Zongjin Li
    • 2
    • 4
    Email author
  1. 1.State Key Lab of Experimental Hematology, Institute of Hematology and Blood Diseases HospitalChinese Academy of Medical SciencesTianjinChina
  2. 2.Collaborative Innovation Center for BiotherapyNankai University School of MedicineTianjinChina
  3. 3.Department of TraumatologyBeijing Water Resources HospitalBeijingChina
  4. 4.The Key Laboratory of Bioactive Materials, Ministry of EducationNankai University, the College of Life ScienceTianjinChina

Personalised recommendations