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
- 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 - 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 - Hanson, C. & Caisander, G. Human embryonic stem cells and chromosome stability. APMIS 113, 751–755 (2005).
Article Google Scholar - 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 - 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 - Redon, R. et al. Global variation in copy number in the human genome. Nature 444, 444–454 (2006).
Article CAS Google Scholar - 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 - Iafrate, A.J. et al. Detection of large-scale variation in the human genome. Nat. Genet. 36, 949–951 (2004).
Article CAS Google Scholar - Sebat, J. et al. Large-scale copy number polymorphism in the human genome. Science 305, 525–528 (2004).
Article CAS Google Scholar - Futreal, P.A. et al. A census of human cancer genes. Nat. Rev. Cancer 4, 177–183 (2004).
Article CAS Google Scholar - Kallioniemi, A. CGH microarrays and cancer. Curr. Opin. Biotechnol. 19, 36–40 (2008).
Article CAS Google Scholar - 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 - 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 - 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 - 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 - 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 - Maitra, A. et al. Genomic alterations in cultured human embryonic stem cells. Nat. Genet. 37, 1099–1103 (2005).
Article CAS Google Scholar - 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 - Wu, H. et al. Copy number variant analysis of human embryonic stem cells. Stem Cells 26, 1484–1489 (2008).
Article CAS Google Scholar - Spits, C. et al. Recurrent chromosomal abnormalities in human embryonic stem cells. Nat. Biotechnol. 12, 1361–1363 (2008).
Article Google Scholar - Hubbard, T.J. et al. Ensembl 2007. Nucleic Acids Res. 35, D610–D617 (2007).
Article CAS Google Scholar - 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 - 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 - 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 - 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 - 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 - 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 - 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 - 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 - 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 - 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 - Hastings, P.J. Adaptive amplification. Crit. Rev. Biochem. Mol. Biol. 42, 271–283 (2007).
Article CAS Google Scholar - 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 - 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 - The International HapMap Consortium The international HapMap project. Nature 426, 789–796 (2003).
- Eyre, T.A. et al. The HUGO gene nomenclature database, 2006 updates. Nucleic Acids Res. 34, D319–D321 (2006).
Article CAS Google Scholar - Dai, M. et al. Evolving gene/transcript definitions significantly alter the interpretation of GeneChip data. Nucleic Acids Res. 33, e175 (2005).
Article Google Scholar - 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).
- 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 - 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 - 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 - 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
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
- Turku Centre for Biotechnology, University of Turku and Åbo Akademi University, Turku, Finland
Elisa Närvä, Reija Autio, Nelly Rahkonen, Omid Rasool & Riitta Lahesmaa - Department of Signal Processing, Tampere University of Technology, Tampere, Finland
Reija Autio, Lingjia Kong & Olli Yli-Harja - Centre for Stem Cell Biology and the Department of Biomedical Science, University of Sheffield, Sheffield, UK
Neil Harrison & Peter W Andrews - Stem Cell Technologies Ltd., Jerusalem, Israel
Danny Kitsberg - Institute of Reconstructive Neurobiology, Life & Brain Center, University of Bonn and Hertie Foundation, Bonn, Germany
Lodovica Borghese & Oliver Brüstle - Technion-Israel Institute of Technology and Department of Obstetrics and Gynecology, Faculty of Medicine, Rambam Health Care Campus, Haifa, Israel
Joseph Itskovitz-Eldor - 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 - Department CLINTEC, Karolinska Institutet, Karolinska University Hospital Huddinge, Stockholm, Sweden
Outi Hovatta - Program of Molecular Neurology, Biomedicum Stem Cell Center, University of Helsinki, Helsinki, Finland
Timo Otonkoski & Timo Tuuri - Children's Hospital, University of Helsinki, Helsinki, Finland
Timo Otonkoski - Institute of Reproductive and Developmental Biology, Faculty of Medicine, Imperial College London, Hammersmith Campus, London, UK
Wei Cui - Sheffield Diagnostic Genetic Services, Sheffield Children's NHS Trust, Sheffield, UK
Duncan Baker & Edna Maltby - Centre for Stem Cell Biology and the Department of Molecular Biology and Biotechnology, University of Sheffield, Sheffield, UK
Harry D Moore - Department of Genetics, Stem Cell Unit, The Institute of Life Sciences, The Hebrew University, Jerusalem, Israel
Nissim Benvenisty - Institute for Systems Biology, Seattle, Washington, USA
Olli Yli-Harja
Authors
- Elisa Närvä
You can also search for this author inPubMed Google Scholar - Reija Autio
You can also search for this author inPubMed Google Scholar - Nelly Rahkonen
You can also search for this author inPubMed Google Scholar - Lingjia Kong
You can also search for this author inPubMed Google Scholar - Neil Harrison
You can also search for this author inPubMed Google Scholar - Danny Kitsberg
You can also search for this author inPubMed Google Scholar - Lodovica Borghese
You can also search for this author inPubMed Google Scholar - Joseph Itskovitz-Eldor
You can also search for this author inPubMed Google Scholar - Omid Rasool
You can also search for this author inPubMed Google Scholar - Petr Dvorak
You can also search for this author inPubMed Google Scholar - Outi Hovatta
You can also search for this author inPubMed Google Scholar - Timo Otonkoski
You can also search for this author inPubMed Google Scholar - Timo Tuuri
You can also search for this author inPubMed Google Scholar - Wei Cui
You can also search for this author inPubMed Google Scholar - Oliver Brüstle
You can also search for this author inPubMed Google Scholar - Duncan Baker
You can also search for this author inPubMed Google Scholar - Edna Maltby
You can also search for this author inPubMed Google Scholar - Harry D Moore
You can also search for this author inPubMed Google Scholar - Nissim Benvenisty
You can also search for this author inPubMed Google Scholar - Peter W Andrews
You can also search for this author inPubMed Google Scholar - Olli Yli-Harja
You can also search for this author inPubMed Google Scholar - 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
- Received: 24 June 2009
- Accepted: 16 February 2010
- Published: 28 March 2010
- Issue Date: April 2010
- DOI: https://doi.org/10.1038/nbt.1615