High-resolution DNA analysis of human embryonic stem cell lines reveals culture-induced copy number changes and loss of heterozygosity (original) (raw)

Accession codes

Accessions

Gene Expression Omnibus

References

  1. Draper, J.S., Moore, H.D., Ruban, L.N., Gokhale, P.J. & Andrews, P.W. Culture and characterization of human embryonic stem cells. Stem Cells Dev. 13, 325–336 (2004).
    Article CAS Google Scholar
  2. Draper, J.S. et al. Recurrent gain of chromosomes 17q and 12 in cultured human embryonic stem cells. Nat. Biotechnol. 22, 53–54 (2004).
    Article CAS Google Scholar
  3. Hanson, C. & Caisander, G. Human embryonic stem cells and chromosome stability. APMIS 113, 751–755 (2005).
    Article Google Scholar
  4. Enver, T. et al. Cellular differentiation hierarchies in normal and culture-adapted human embryonic stem cells. Hum. Mol. Genet. 14, 3129–3140 (2005).
    Article CAS Google Scholar
  5. Baker, D.E. et al. Adaptation to culture of human embryonic stem cells and oncogenesis in vivo. Nat. Biotechnol. 25, 207–215 (2007).
    Article CAS Google Scholar
  6. Redon, R. et al. Global variation in copy number in the human genome. Nature 444, 444–454 (2006).
    Article CAS Google Scholar
  7. Feuk, L., Carson, A.R. & Scherer, S.W. Structural variation in the human genome. Nat. Rev. Genet. 7, 85–97 (2006).
    Article CAS Google Scholar
  8. Iafrate, A.J. et al. Detection of large-scale variation in the human genome. Nat. Genet. 36, 949–951 (2004).
    Article CAS Google Scholar
  9. Sebat, J. et al. Large-scale copy number polymorphism in the human genome. Science 305, 525–528 (2004).
    Article CAS Google Scholar
  10. Futreal, P.A. et al. A census of human cancer genes. Nat. Rev. Cancer 4, 177–183 (2004).
    Article CAS Google Scholar
  11. Kallioniemi, A. CGH microarrays and cancer. Curr. Opin. Biotechnol. 19, 36–40 (2008).
    Article CAS Google Scholar
  12. Jong, K. et al. Cross-platform array comparative genomic hybridization meta-analysis separates hematopoietic and mesenchymal from epithelial tumors. Oncogene 26, 1499–1506 (2007).
    Article CAS Google Scholar
  13. Zheng, H.T., Peng, Z.H., Li, S. & He, L. Loss of heterozygosity analyzed by single nucleotide polymorphism array in cancer. World J. Gastroenterol. 11, 6740–6744 (2005).
    Article CAS Google Scholar
  14. Cervantes, R.B., Stringer, J.R., Shao, C., Tischfield, J.A. & Stambrook, P.J. Embryonic stem cells and somatic cells differ in mutation frequency and type. Proc. Natl. Acad. Sci. USA 99, 3586–3590 (2002).
    Article CAS Google Scholar
  15. Donahue, S.L., Lin, Q., Cao, S. & Ruley, H.E. Carcinogens induce genome-wide loss of heterozygosity in normal stem cells without persistent chromosomal instability. Proc. Natl. Acad. Sci. USA 103, 11642–11646 (2006).
    Article CAS Google Scholar
  16. Inzunza, J. et al. Comparative genomic hybridization and karyotyping of human embryonic stem cells reveals the occurrence of an isodicentric X chromosome after long-term cultivation. Mol. Hum. Reprod. 10, 461–466 (2004).
    Article CAS Google Scholar
  17. Maitra, A. et al. Genomic alterations in cultured human embryonic stem cells. Nat. Genet. 37, 1099–1103 (2005).
    Article CAS Google Scholar
  18. Caisander, G. et al. Chromosomal integrity maintained in five human embryonic stem cell lines after prolonged in vitro culture. Chromosome Res. 14, 131–137 (2006).
    Article CAS Google Scholar
  19. Wu, H. et al. Copy number variant analysis of human embryonic stem cells. Stem Cells 26, 1484–1489 (2008).
    Article CAS Google Scholar
  20. Spits, C. et al. Recurrent chromosomal abnormalities in human embryonic stem cells. Nat. Biotechnol. 12, 1361–1363 (2008).
    Article Google Scholar
  21. Hubbard, T.J. et al. Ensembl 2007. Nucleic Acids Res. 35, D610–D617 (2007).
    Article CAS Google Scholar
  22. Monk, M., Hitchins, M. & Hawes, S. Differential expression of the embryo/cancer gene ECSA(DPPA2), the cancer/testis gene BORIS and the pluripotency structural gene OCT4, in human preimplantation development. Mol. Hum. Reprod. 14, 347–355 (2008).
    Article CAS Google Scholar
  23. Lindblom, A., Rotstein, S., Skoog, L., Nordenskjold, M. & Larsson, C. Deletions on chromosome 16 in primary familial breast carcinomas are associated with development of distant metastases. Cancer Res. 53, 3707–3711 (1993).
    CAS PubMed Google Scholar
  24. Cleton-Jansen, A.M. et al. Different mechanisms of chromosome 16 loss of heterozygosity in well- versus poorly differentiated ductal breast cancer. Genes Chromosom. Cancer 41, 109–116 (2004).
    Article CAS Google Scholar
  25. Carter, B.S. et al. Allelic loss of chromosomes 16q and 10q in human prostate cancer. Proc. Natl. Acad. Sci. USA 87, 8751–8755 (1990).
    Article CAS Google Scholar
  26. Jenner, M.W. et al. Gene mapping and expression analysis of 16q loss of heterozygosity identifies WWOX and CYLD as being important in determining clinical outcome in multiple myeloma. Blood 110, 3291–3300 (2007).
    Article CAS Google Scholar
  27. Mortensen, R.M., Conner, D.A., Chao, S., Geisterfer-Lowrance, A.A. & Seidman, J.G. Production of homozygous mutant ES cells with a single targeting construct. Mol. Cell. Biol. 12, 2391–2395 (1992).
    Article CAS Google Scholar
  28. Lefort, N. et al. Human embryonic stem cells reveal recurrent genomic instability at 20q11.21. Nat. Biotechnol. 26, 1364–1366 (2008).
    Article CAS Google Scholar
  29. Mantel, C. et al. Checkpoint-apoptosis uncoupling in human and mouse embryonic stem cells: a source of karyotpic instability. Blood 109, 4518–4527 (2007).
    Article CAS Google Scholar
  30. Rodriguez-Jimenez, F.J., Moreno-Manzano, V., Lucas-Dominguez, R. & Sanchez-Puelles, J.M. Hypoxia causes downregulation of mismatch repair system and genomic instability in stem cells. Stem Cells 26, 2052–2062 (2008).
    Article CAS Google Scholar
  31. Garcia-Perez, J.L. et al. LINE-1 retrotransposition in human embryonic stem cells. Hum. Mol. Genet. 16, 1569–1577 (2007).
    Article CAS Google Scholar
  32. Hastings, P.J. Adaptive amplification. Crit. Rev. Biochem. Mol. Biol. 42, 271–283 (2007).
    Article CAS Google Scholar
  33. Osafune, K. et al. Marked differences in differentiation propensity among human embryonic stem cell lines. Nat. Biotechnol. 26, 313–315 (2008).
    Article CAS Google Scholar
  34. Andrews, P.W. et al. Embryonic stem (ES) cells and embryonal carcinoma (EC) cells: opposite sides of the same coin. Biochem. Soc. Trans. 33, 1526–1530 (2005).
    Article CAS Google Scholar
  35. The International HapMap Consortium The international HapMap project. Nature 426, 789–796 (2003).
  36. Eyre, T.A. et al. The HUGO gene nomenclature database, 2006 updates. Nucleic Acids Res. 34, D319–D321 (2006).
    Article CAS Google Scholar
  37. Dai, M. et al. Evolving gene/transcript definitions significantly alter the interpretation of GeneChip data. Nucleic Acids Res. 33, e175 (2005).
    Article Google Scholar
  38. Bengtsson, H., Simpson, K., Bullard, J. & Hansen, K. . Aroma.Affymetrix: A Generic Framework In R For Analyzing Small To Very Large Affymetrix Data Sets In Bounded Memory. Technical report 745. (Department of Statistics, University of California, Berkeley, 2008).
  39. Bolstad, B.M., Irizarry, R.A., Astrand, M. & Speed, T.P. A comparison of normalization methods for high density oligonucleotide array data based on variance and bias. Bioinformatics 19, 185–193 (2003).
    Article CAS Google Scholar
  40. Hautaniemi, S. et al. A strategy for identifying putative causes of gene expression variation in human cancers. J. Franklin Inst. 341, 77–88 (2004).
    Article Google Scholar
  41. Benjamini, Y. & Hochberg, Y. Controlling the false discovery rate: a practical and powerful approach to multiple testing. J. R. Stat. Soc., B 57, 289–300 (1995).
    Google Scholar
  42. Jarvinen, A.K. et al. Identification of target genes in laryngeal squamous cell carcinoma by high-resolution copy number and gene expression microarray analyses. Oncogene 25, 6997–7008 (2006).
    Article Google Scholar

Download references

Acknowledgements

We are grateful to everyone who has taken care of sample collection and handling: T. Golan-Lev, A. Urrutikoetxea-Uriguen, S. Haupt, P. Koch, I. Laufenberg, B. Ley, A. Hampl, M. Vodinska, K. Koudelkova, S. Ström, F. Holm, A.-M. Strömberg, C. Olsson, M. Mikkola, S. Vuoristo, P. Junni and M. Hakkarainen. We especially acknowledge M. Linja, T. Heinonen and the Finnish DNA Microarray Centre for their excellent technical assistance. We acknowledge the Turku Graduate School of Biomedical Sciences. This study is supported by funding for the ESTOOLS consortium under the Sixth Research Framework Programme of the European Union, Juvenile Diabetes Research Foundation, The Academy of Finland and the Finnish Cancer Organizations, The Improving Outcomes Guidance Trust, The Ministry of Education, Youth, and Sport of the Czech Republic, Ida Montin Foundation, The Academy of Finland, projects no. 129657 (Finnish Centre of Excellence program 2006-11) and no. 134117 and the Medical Research Council, UK.

Author information

Authors and Affiliations

  1. Turku Centre for Biotechnology, University of Turku and Åbo Akademi University, Turku, Finland
    Elisa Närvä, Reija Autio, Nelly Rahkonen, Omid Rasool & Riitta Lahesmaa
  2. Department of Signal Processing, Tampere University of Technology, Tampere, Finland
    Reija Autio, Lingjia Kong & Olli Yli-Harja
  3. Centre for Stem Cell Biology and the Department of Biomedical Science, University of Sheffield, Sheffield, UK
    Neil Harrison & Peter W Andrews
  4. Stem Cell Technologies Ltd., Jerusalem, Israel
    Danny Kitsberg
  5. Institute of Reconstructive Neurobiology, Life & Brain Center, University of Bonn and Hertie Foundation, Bonn, Germany
    Lodovica Borghese & Oliver Brüstle
  6. Technion-Israel Institute of Technology and Department of Obstetrics and Gynecology, Faculty of Medicine, Rambam Health Care Campus, Haifa, Israel
    Joseph Itskovitz-Eldor
  7. Department of Biology, Masaryk University & Department of Molecular Embryology, Faculty of Medicine, Institute of Experimental Medicine, Academy of Sciences of the Czech Republic, Brno, Czech Republic
    Petr Dvorak
  8. Department CLINTEC, Karolinska Institutet, Karolinska University Hospital Huddinge, Stockholm, Sweden
    Outi Hovatta
  9. Program of Molecular Neurology, Biomedicum Stem Cell Center, University of Helsinki, Helsinki, Finland
    Timo Otonkoski & Timo Tuuri
  10. Children's Hospital, University of Helsinki, Helsinki, Finland
    Timo Otonkoski
  11. Institute of Reproductive and Developmental Biology, Faculty of Medicine, Imperial College London, Hammersmith Campus, London, UK
    Wei Cui
  12. Sheffield Diagnostic Genetic Services, Sheffield Children's NHS Trust, Sheffield, UK
    Duncan Baker & Edna Maltby
  13. Centre for Stem Cell Biology and the Department of Molecular Biology and Biotechnology, University of Sheffield, Sheffield, UK
    Harry D Moore
  14. Department of Genetics, Stem Cell Unit, The Institute of Life Sciences, The Hebrew University, Jerusalem, Israel
    Nissim Benvenisty
  15. Institute for Systems Biology, Seattle, Washington, USA
    Olli Yli-Harja

Authors

  1. Elisa Närvä
    You can also search for this author inPubMed Google Scholar
  2. Reija Autio
    You can also search for this author inPubMed Google Scholar
  3. Nelly Rahkonen
    You can also search for this author inPubMed Google Scholar
  4. Lingjia Kong
    You can also search for this author inPubMed Google Scholar
  5. Neil Harrison
    You can also search for this author inPubMed Google Scholar
  6. Danny Kitsberg
    You can also search for this author inPubMed Google Scholar
  7. Lodovica Borghese
    You can also search for this author inPubMed Google Scholar
  8. Joseph Itskovitz-Eldor
    You can also search for this author inPubMed Google Scholar
  9. Omid Rasool
    You can also search for this author inPubMed Google Scholar
  10. Petr Dvorak
    You can also search for this author inPubMed Google Scholar
  11. Outi Hovatta
    You can also search for this author inPubMed Google Scholar
  12. Timo Otonkoski
    You can also search for this author inPubMed Google Scholar
  13. Timo Tuuri
    You can also search for this author inPubMed Google Scholar
  14. Wei Cui
    You can also search for this author inPubMed Google Scholar
  15. Oliver Brüstle
    You can also search for this author inPubMed Google Scholar
  16. Duncan Baker
    You can also search for this author inPubMed Google Scholar
  17. Edna Maltby
    You can also search for this author inPubMed Google Scholar
  18. Harry D Moore
    You can also search for this author inPubMed Google Scholar
  19. Nissim Benvenisty
    You can also search for this author inPubMed Google Scholar
  20. Peter W Andrews
    You can also search for this author inPubMed Google Scholar
  21. Olli Yli-Harja
    You can also search for this author inPubMed Google Scholar
  22. Riitta Lahesmaa
    You can also search for this author inPubMed Google Scholar

Contributions

E.N., R.A., N.B., P.W.A., O.Y.-H. and R.L. designed the experiments, E.N. and R.L. were responsible for the coordination of the project and microarray experiments. R.A., E.N. and O.Y.-H. were responsible for data analysis, integration and statistical analysis. N.R. performed RNA extractions. L.K. built the gene annotation list of genes overlapping CNVs. D.B. performed conventional karyotyping. E.N. and N.R. performed copy-number state validations with RT-PCR. J.I.-E. provided I3 and I6 lines for the study. P.D., O.H., T.O., T.T., N.B., W.C., O.B., E.M., H.D.M., P.W.A., O.Y.-H. and R.L. provided the samples and coordinated the project in their groups. E.N., R.A., N.R., L.K., N.H., D.K., L.B., J.I.-E., O.R., P.D., O.H., T.O., T.T., N.B., W.C., O.B., D.B., E.M., H.D.M., P.W.A., O.Y.-H. and R.L. contributed to writing the paper.

Corresponding authors

Correspondence toElisa Närvä or Riitta Lahesmaa.

Ethics declarations

Competing interests

D.K. is affiliated with Stem Cell Technologies, Ltd. (However, the study was not supported by the company.)

Supplementary information

Rights and permissions

About this article

Cite this article

Närvä, E., Autio, R., Rahkonen, N. et al. High-resolution DNA analysis of human embryonic stem cell lines reveals culture-induced copy number changes and loss of heterozygosity.Nat Biotechnol 28, 371–377 (2010). https://doi.org/10.1038/nbt.1615

Download citation