Table of Contents Author Guidelines Submit a Manuscript
Stem Cells International
Volume 2016, Article ID 3826249, 14 pages
http://dx.doi.org/10.1155/2016/3826249
Research Article

High-Fidelity Reprogrammed Human IPSCs Have a High Efficacy of DNA Repair and Resemble hESCs in Their MYC Transcriptional Signature

1Department of Radiation Oncology, University of Maryland School of Medicine, Baltimore, MD 21201, USA
2Institute for Cell Engineering and Sidney Kimmel Comprehensive Cancer Center, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA

Received 18 March 2016; Revised 23 June 2016; Accepted 14 July 2016

Academic Editor: Silvia Brunelli

Copyright © 2016 Pratik K. Nagaria et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Linked References

  1. C. N. Svendsen, “Back to the future: how human induced pluripotent stem cells will transform regenerative medicine,” Human Molecular Genetics, vol. 22, no. 1, Article ID ddt379, pp. R32–R38, 2013. View at Publisher · View at Google Scholar · View at Scopus
  2. A. Trounson, K. A. Shepard, and N. D. DeWitt, “Human disease modeling with induced pluripotent stem cells,” Current Opinion in Genetics and Development, vol. 22, no. 5, pp. 509–516, 2012. View at Publisher · View at Google Scholar · View at Scopus
  3. B. Feng, J.-H. Ng, J.-C. D. Heng, and H.-H. Ng, “Molecules that promote or enhance reprogramming of somatic cells to induced pluripotent stem cells,” Cell Stem Cell, vol. 4, no. 4, pp. 301–312, 2009. View at Publisher · View at Google Scholar · View at Scopus
  4. K. Tanabe, M. Nakamura, M. Narita, K. Takahashi, and S. Yamanaka, “Maturation, not initiation, is the major roadblock during reprogramming toward pluripotency from human fibroblasts,” Proceedings of the National Academy of Sciences of the United States of America, vol. 110, no. 30, pp. 12172–12179, 2013. View at Publisher · View at Google Scholar · View at Scopus
  5. I. Wilmut, G. Sullivan, and I. Chambers, “The evolving biology of cell reprogramming,” Philosophical Transactions of the Royal Society B: Biological Sciences, vol. 366, no. 1575, pp. 2183–2197, 2011. View at Publisher · View at Google Scholar · View at Scopus
  6. Y. Xu, X. Wei, M. Wang et al., “Proliferation rate of somatic cells affects reprogramming efficiency,” Journal of Biological Chemistry, vol. 288, no. 14, pp. 9767–9778, 2013. View at Publisher · View at Google Scholar · View at Scopus
  7. U. Ben-David, N. Benvenisty, and Y. Mayshar, “Genetic instability in human induced pluripotent stem cells: classification of causes and possible safeguards,” Cell Cycle, vol. 9, no. 23, pp. 4603–4604, 2010. View at Publisher · View at Google Scholar · View at Scopus
  8. A. Gore, Z. Li, H.-L. Fung et al., “Somatic coding mutations in human induced pluripotent stem cells,” Nature, vol. 471, no. 7336, pp. 63–67, 2011. View at Publisher · View at Google Scholar · View at Scopus
  9. S. M. Hussein, N. N. Batada, S. Vuoristo et al., “Copy number variation and selection during reprogramming to pluripotency,” Nature, vol. 471, no. 7336, pp. 58–62, 2011. View at Publisher · View at Google Scholar · View at Scopus
  10. Y. Mayshar, U. Ben-David, N. Lavon et al., “Identification and classification of chromosomal aberrations in human induced pluripotent stem cells,” Cell Stem Cell, vol. 7, no. 4, pp. 521–531, 2010. View at Publisher · View at Google Scholar · View at Scopus
  11. D. A. Robinton and G. Q. Daley, “The promise of induced pluripotent stem cells in research and therapy,” Nature, vol. 481, no. 7381, pp. 295–305, 2012. View at Publisher · View at Google Scholar · View at Scopus
  12. T. S. Park, J. S. Huo, A. Peters et al., “Growth factor-activated stem cell circuits and stromal signals cooperatively accelerate non-integrated iPSC reprogramming of human myeloid progenitors,” PLoS ONE, vol. 7, no. 8, Article ID e42838, 2012. View at Publisher · View at Google Scholar · View at Scopus
  13. R. Sridharan, J. Tchieu, M. J. Mason et al., “Role of the murine reprogramming factors in the induction of pluripotency,” Cell, vol. 136, no. 2, pp. 364–377, 2009. View at Publisher · View at Google Scholar · View at Scopus
  14. X. Chen, H. Xu, P. Yuan et al., “Integration of external signaling pathways with the core transcriptional network in embryonic stem cells,” Cell, vol. 133, no. 6, pp. 1106–1117, 2008. View at Publisher · View at Google Scholar · View at Scopus
  15. R. L. Judson, J. E. Babiarz, M. Venere, and R. Blelloch, “Embryonic stem cell-specific microRNAs promote induced pluripotency,” Nature Biotechnology, vol. 27, no. 5, pp. 459–461, 2009. View at Publisher · View at Google Scholar · View at Scopus
  16. N. Hyka-Nouspikel, J. Desmarais, P. J. Gokhale et al., “Deficient DNA damage response and cell cycle checkpoints lead to accumulation of point mutations in human embryonic stem cells,” STEM CELLS, vol. 30, no. 9, pp. 1901–1910, 2012. View at Publisher · View at Google Scholar · View at Scopus
  17. P. Nagaria, C. Robert, and F. V. Rassool, “DNA double-strand break response in stem cells: mechanisms to maintain genomic integrity,” Biochimica et Biophysica Acta (BBA)—General Subjects, vol. 1830, no. 2, pp. 2345–2353, 2013. View at Publisher · View at Google Scholar · View at Scopus
  18. T. Helleday, “Pathways for mitotic homologous recombination in mammalian cells,” Mutation Research/Fundamental and Molecular Mechanisms of Mutagenesis, vol. 532, no. 1-2, pp. 103–115, 2003. View at Publisher · View at Google Scholar · View at Scopus
  19. F. V. Rassool and A. E. Tomkinson, “Targeting abnormal DNA double strand break repair in cancer,” Cellular and Molecular Life Sciences, vol. 67, no. 21, pp. 3699–3710, 2010. View at Publisher · View at Google Scholar · View at Scopus
  20. J. Fan, C. Robert, Y.-Y. Jang et al., “Human induced pluripotent cells resemble embryonic stem cells demonstrating enhanced levels of DNA repair and efficacy of nonhomologous end-joining,” Mutation Research, vol. 713, no. 1-2, pp. 8–17, 2011. View at Publisher · View at Google Scholar · View at Scopus
  21. L. Serrano, L. Liang, Y. Chang et al., “Homologous recombination conserves DNA sequence integrity throughout the cell cycle in embryonic stem cells,” Stem Cells and Development, vol. 20, no. 2, pp. 363–374, 2011. View at Publisher · View at Google Scholar · View at Scopus
  22. L. Z. Luo, S. Gopalakrishna-Pillai, S. L. Nay et al., “DNA repair in human pluripotent stem cells is distinct from that in non-pluripotent human cells,” PLoS ONE, vol. 7, no. 3, article e30541, 2012. View at Publisher · View at Google Scholar · View at Scopus
  23. V. Ramos-Mejia, M. Mũoz-Lopez, J. L. Garcia-Perez, and P. Menendez, “iPSC lines that do not silence the expression of the ectopic reprogramming factors may display enhanced propensity to genomic instability,” Cell Research, vol. 20, no. 10, pp. 1092–1095, 2010. View at Publisher · View at Google Scholar · View at Scopus
  24. F. J. Molina-Estevez, M. L. Lozano, S. Navarro et al., “Brief report: impaired cell reprogramming in nonhomologous end joining deficient cells,” Stem Cells, vol. 31, no. 8, pp. 1726–1730, 2013. View at Publisher · View at Google Scholar · View at Scopus
  25. C. Y. Lin, J. Lovén, P. B. Rahl et al., “Transcriptional amplification in tumor cells with elevated c-Myc,” Cell, vol. 151, no. 1, pp. 56–67, 2012. View at Publisher · View at Google Scholar · View at Scopus
  26. K. R. Luoto, A. X. Meng, A. R. Wasylishen et al., “Tumor cell kill by c-MYC depletion: role of MYC-regulated genes that control DNA double-strand break repair,” Cancer Research, vol. 70, no. 21, pp. 8748–8759, 2010. View at Publisher · View at Google Scholar · View at Scopus
  27. J. A. Byrne, H. N. Nguyen, and R. A. Reijo Pera, “Enhanced generation of induced pluripotent stem cells from a subpopulation of human fibroblasts,” PLoS ONE, vol. 4, no. 9, article e7118, 2009. View at Publisher · View at Google Scholar · View at Scopus
  28. P. W. Burridge, S. Thompson, M. A. Millrod et al., “A universal system for highly efficient cardiac differentiation of human induced pluripotent stem cells that eliminates interline variability,” PLoS ONE, vol. 6, no. 4, Article ID e18293, 2011. View at Publisher · View at Google Scholar · View at Scopus
  29. K. Hu, J. Yu, K. Suknuntha et al., “Efficient generation of transgene-free induced pluripotent stem cells from normal and neoplastic bone marrow and cord blood mononuclear cells,” Blood, vol. 117, no. 14, pp. e109–e119, 2011. View at Publisher · View at Google Scholar · View at Scopus
  30. L. A. Tobin, C. Robert, P. Nagaria et al., “Targeting abnormal DNA repair in therapy-resistant breast cancers,” Molecular Cancer Research, vol. 10, no. 1, pp. 96–107, 2012. View at Publisher · View at Google Scholar · View at Scopus
  31. N. Bennardo, A. Cheng, N. Huang, and J. M. Stark, “Alternative-NHEJ is a mechanistically distinct pathway of mammalian chromosome break repair,” PLoS Genetics, vol. 4, no. 6, Article ID e1000110, 2008. View at Publisher · View at Google Scholar · View at Scopus
  32. J.-H. Chen, C. N. Hales, and S. E. Ozanne, “DNA damage, cellular senescence and organismal ageing: causal or correlative?” Nucleic Acids Research, vol. 35, no. 22, pp. 7417–7428, 2007. View at Publisher · View at Google Scholar · View at Scopus
  33. A. Seluanov, D. Mittelman, O. M. Pereira-Smith, J. H. Wilson, and V. Gorbunova, “DNA end joining becomes less efficient and more error-prone during cellular senescence,” Proceedings of the National Academy of Sciences of the United States of America, vol. 101, no. 20, pp. 7624–7629, 2004. View at Publisher · View at Google Scholar · View at Scopus
  34. O. Momcilovic, L. Knobloch, J. Fornsaglio, S. Varum, C. Easley, and G. Schatten, “DNA damage responses in human induced pluripotent stem cells and embryonic stem cells,” PLoS ONE, vol. 5, no. 10, Article ID e13410, 2010. View at Publisher · View at Google Scholar · View at Scopus
  35. C. Thiriet and J. J. Hayes, “Chromatin in need of a fix: phosphorylation of H2AX connects chromatin to DNA repair,” Molecular Cell, vol. 18, no. 6, pp. 617–622, 2005. View at Publisher · View at Google Scholar · View at Scopus
  36. Y. Xu and D. Baltimore, “Dual roles of ATM in the cellular response to radiation and in cell growth control,” Genes and Development, vol. 10, no. 19, pp. 2401–2410, 1996. View at Publisher · View at Google Scholar · View at Scopus
  37. M. Ashcroft, M. H. G. Kubbutat, and K. H. Vousden, “Regulation of p53 function and stability by phosphorylation,” Molecular and Cellular Biology, vol. 19, no. 3, pp. 1751–1758, 1999. View at Publisher · View at Google Scholar · View at Scopus
  38. A. Gunn and J. M. Stark, “I-SceI-based assays to examine distinct repair outcomes of mammalian chromosomal double strand breaks,” Methods in Molecular Biology, vol. 920, pp. 379–391, 2012. View at Publisher · View at Google Scholar · View at Scopus
  39. J. Kim, A. J. Woo, J. Chu et al., “A Myc network accounts for similarities between embryonic stem and cancer cell transcription programs,” Cell, vol. 143, no. 2, pp. 313–324, 2010. View at Publisher · View at Google Scholar · View at Scopus
  40. M. Nakagawa, M. Koyanagi, K. Tanabe et al., “Generation of induced pluripotent stem cells without Myc from mouse and human fibroblasts,” Nature Biotechnology, vol. 26, no. 1, pp. 101–106, 2008. View at Publisher · View at Google Scholar · View at Scopus
  41. H. Wang, D. I. Hammoudeh, A. V. Follis et al., “Improved low molecular weight Myc-Max inhibitors,” Molecular Cancer Therapeutics, vol. 6, no. 9, pp. 2399–2408, 2007. View at Publisher · View at Google Scholar · View at Scopus
  42. S. M. Taapken, B. S. Nisler, M. A. Newton et al., “Karotypic abnormalities in human induced pluripotent stem cells and embryonic stem cells,” Nature Biotechnology, vol. 29, no. 4, pp. 313–314, 2011. View at Publisher · View at Google Scholar · View at Scopus
  43. L. C. Laurent, I. Ulitsky, I. Slavin et al., “Dynamic changes in the copy number of pluripotency and cell proliferation genes in human ESCs and iPSCs during reprogramming and time in culture,” Cell Stem Cell, vol. 8, no. 1, pp. 106–118, 2011. View at Publisher · View at Google Scholar · View at Scopus
  44. F. González, D. Georgieva, F. Vanoli et al., “Homologous recombination DNA repair genes play a critical role in reprogramming to a pluripotent state,” Cell Reports, vol. 3, no. 3, pp. 651–660, 2013. View at Publisher · View at Google Scholar · View at Scopus
  45. T. Kawamura, J. Suzuki, Y. V. Wang et al., “Linking the p53 tumour suppressor pathway to somatic cell reprogramming,” Nature, vol. 460, no. 7259, pp. 1140–1144, 2009. View at Publisher · View at Google Scholar · View at Scopus
  46. S.-H. Chiou, B.-H. Jiang, Y.-L. Yu et al., “Poly(ADP-ribose) polymerase 1 regulates nuclear reprogramming and promotes iPSC generation without c-Myc,” Journal of Experimental Medicine, vol. 210, no. 1, pp. 85–98, 2013. View at Publisher · View at Google Scholar · View at Scopus
  47. T. Kinoshita, G. Nagamatsu, T. Kosaka et al., “Ataxia-telangiectasia mutated (ATM) deficiency decreases reprogramming efficiency and leads to genomic instability in iPS cells,” Biochemical and Biophysical Research Communications, vol. 407, no. 2, pp. 321–326, 2011. View at Publisher · View at Google Scholar · View at Scopus
  48. F. J. Molina-Estevez, M. L. Lozano, S. Navarro et al., “Impaired cell reprogramming in non-homologous end joining deficient cells,” STEM CELLS, vol. 31, no. 8, pp. 1726–1730, 2013. View at Publisher · View at Google Scholar · View at Scopus
  49. K. Tilgner, I. Neganova, I. Moreno-Gimeno et al., “A human iPSC model of Ligase IV deficiency reveals an important role for NHEJ-mediated-DSB repair in the survival and genomic stability of induced pluripotent stem cells and emerging haematopoietic progenitors,” Cell Death and Differentiation, vol. 20, no. 8, pp. 1089–1100, 2013. View at Publisher · View at Google Scholar · View at Scopus
  50. S. K. Yung, K. Tilgner, M. H. Ledran et al., “Brief report: human pluripotent stem cell models of fanconi anemia deficiency reveal an important role for fanconi anemia proteins in cellular reprogramming and survival of hematopoietic progenitors,” STEM CELLS, vol. 31, no. 5, pp. 1022–1029, 2013. View at Publisher · View at Google Scholar · View at Scopus
  51. J. B. Kim, H. Zaehres, G. Wu et al., “Pluripotent stem cells induced from adult neural stem cells by reprogramming with two factors,” Nature, vol. 454, no. 7204, pp. 646–650, 2008. View at Publisher · View at Google Scholar · View at Scopus
  52. T. S. Park, I. Bhutto, L. Zimmerlin et al., “Vascular progenitors from cord blood-derived induced pluripotent stem cells possess augmented capacity for regenerating ischemic retinal vasculature,” Circulation, vol. 129, no. 3, pp. 359–372, 2014. View at Publisher · View at Google Scholar · View at Scopus
  53. A. N. Bogomazova, M. A. Lagarkova, L. V. Tskhovrebova, M. V. Shutova, and S. L. Kiselev, “Error-prone nonhomologous end joining repair operates in human pluripotent stem cells during late G2,” Aging, vol. 3, no. 6, pp. 584–596, 2011. View at Publisher · View at Google Scholar · View at Scopus
  54. N. Bennardo and J. M. Stark, “ATM limits incorrect end utilization during non- homologous end joining of multiple chromosome breaks,” PLoS Genetics, vol. 6, no. 11, article e1001194, 2010. View at Publisher · View at Google Scholar · View at Scopus
  55. A. Gunn, N. Bennardo, A. Cheng, and J. M. Stark, “Correct end use during end joining of multiple chromosomal double strand breaks is influenced by repair protein RAD50, DNA-dependent protein kinase DNA-PKcs, and transcription context,” The Journal of Biological Chemistry, vol. 286, no. 49, pp. 42470–42482, 2011. View at Publisher · View at Google Scholar · View at Scopus
  56. B. R. Adams, A. J. Hawkins, L. F. Povirk, and K. Valerie, “ATM-independent, high-fidelity nonhomologous end joining predominates in human embryonic stem cells,” Aging, vol. 2, no. 9, pp. 582–596, 2010. View at Publisher · View at Google Scholar · View at Scopus
  57. G. Nagamatsu, S. Saito, T. Kosaka et al., “Optimal ratio of transcription factors for somatic cell reprogramming,” Journal of Biological Chemistry, vol. 287, no. 43, pp. 36273–36282, 2012. View at Publisher · View at Google Scholar · View at Scopus
  58. N. V. Varlakhanova, R. F. Cotterman, W. N. deVries et al., “Myc maintains embryonic stem cell pluripotency and self-renewal,” Differentiation, vol. 80, no. 1, pp. 9–19, 2010. View at Publisher · View at Google Scholar · View at Scopus
  59. L. A. Boyer, T. I. Lee, M. F. Cole et al., “Core transcriptional regulatory circuitry in human embryonic stem cells,” Cell, vol. 122, no. 6, pp. 947–956, 2005. View at Publisher · View at Google Scholar · View at Scopus
  60. J. Kim, J. Chu, X. Shen, J. Wang, and S. H. Orkin, “An extended transcriptional network for pluripotency of embryonic stem cells,” Cell, vol. 132, no. 6, pp. 1049–1061, 2008. View at Publisher · View at Google Scholar · View at Scopus
  61. R. M. Marion, K. Strati, H. Li et al., “Telomeres acquire embryonic stem cell characteristics in induced pluripotent stem cells,” Cell Stem Cell, vol. 4, no. 2, pp. 141–154, 2009. View at Publisher · View at Google Scholar · View at Scopus
  62. N. Muvarak, S. Kelley, C. Robert et al., “c-MYC generates repair errors via increased transcription of alternative-NHEJ factors, LIG3 and PARP1, in tyrosine kinase-activated leukemias,” Molecular Cancer Research, vol. 13, no. 4, pp. 699–712, 2015. View at Publisher · View at Google Scholar · View at Scopus