Skip to main content
SpringerLink
Log in

Genomic Integrity of Embryonic and Neural Stem Cells

  • Chapter
  • First Online:
Endogenous Stem Cell-Based Brain Remodeling in Mammals

Part of the book series: Stem Cell Biology and Regenerative Medicine ((STEMCELL))

  • 790 Accesses

Abstract

Substitutive cell therapy using fetal grafts has demonstrated preliminary clinical success in patients with neurological diseases, but the logistics required for accessing fetal cells preclude its extension to the relevant population of patients. Pluripotent stem cell derivatives offer an alternative source of cells for regenerative medicine. However genomic alterations may occur in culture and compromise their proper use in therapy. Recurrent chromosomal defects have been observed both in pluripotent stem cells and in their derivatives. Whether hPSC derivatives can eventually be used widely for therapeutic purposes will depend upon their capacity to pass strict quality controls. As hPSCs and their derivatives can and are often propagated for extended periods of time, these quality controls necessarily include that of genomic integrity. Various techniques are used to monitor genomic integrity of cultured cells. They differ in their sensitivity, their resolution, their cost and their throughput.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 129.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 169.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  • Aasen T, Raya A, Barrero MJ, Garreta E, Consiglio A, Gonzalez F, Vassena R, Bilic J, Pekarik V, Tiscornia G et al (2008) Efficient and rapid generation of induced pluripotent stem cells from human keratinocytes. Nat Biotechnol 26:1276–1284

    CAS  PubMed  Google Scholar 

  • Amps K, Andrews PW, Anyfantis G, Armstrong L, Avery S, Baharvand H, Baker J, Baker D, Munoz MB, Beil S et al (2011) Screening ethnically diverse human embryonic stem cells identifies a chromosome 20 minimal amplicon conferring growth advantage. Nat Biotechnol 29:1132–1144

    CAS  PubMed  Google Scholar 

  • Andrews PW, Matin MM, Bahrami AR, Damjanov I, Gokhale P, Draper JS (2005) Embryonic stem (ES) cells and embryonal carcinoma (EC) cells: opposite sides of the same coin. Biochem Soc Trans 33:1526–1530

    CAS  PubMed  Google Scholar 

  • Arlt MF, Mulle JG, Schaibley VM, Ragland RL, Durkin SG, Warren ST, Glover TW (2009) Replication stress induces genome-wide copy number changes in human cells that resemble polymorphic and pathogenic variants. Am J Hum Genet 84:339–350

    CAS  PubMed Central  PubMed  Google Scholar 

  • Aubry L, Bugi A, Lefort N, Rousseau F, Peschanski M, Perrier AL (2008) Striatal progenitors derived from human ES cells mature into DARPP32 neurons in vitro and in quinolinic acid-lesioned rats. Proc Natl Acad Sci U S A 105:16707–16712

    CAS  PubMed Central  PubMed  Google Scholar 

  • Bai Q, Desprat R, Klein B, Lemaitre JM, De Vos J (2013) Embryonic stem cells or induced pluripotent stem cells? A DNA integrity perspective. Curr Gene Ther 13:93–98

    CAS  PubMed  Google Scholar 

  • Baker DE, Harrison NJ, Maltby E, Smith K, Moore HD, Shaw PJ, Heath PR, Holden H, Andrews PW (2007) Adaptation to culture of human embryonic stem cells and oncogenesis in vivo. Nat Biotechnol 25:207–215

    CAS  PubMed  Google Scholar 

  • Ban H, Nishishita N, Fusaki N, Tabata T, Saeki K, Shikamura M, Takada N, Inoue M, Hasegawa M, Kawamata S, Nishikawa S (2011) Efficient generation of transgene-free human induced pluripotent stem cells (iPSCs) by temperature-sensitive Sendai virus vectors. Proc Natl Acad Sci U S A 108:14234–14239

    CAS  PubMed Central  PubMed  Google Scholar 

  • Ben-David U, Mayshar Y, Benvenisty N (2011) Large-scale analysis reveals acquisition of lineage-specific chromosomal aberrations in human adult stem cells. Cell Stem Cell 9:97–102

    CAS  PubMed  Google Scholar 

  • Brimble SN, Zeng X, Weiler DA, Luo Y, Liu Y, Lyons IG, Freed WJ, Robins AJ, Rao MS, Schulz TC (2004) Karyotypic stability, genotyping, differentiation, feeder-free maintenance, and gene expression sampling in three human embryonic stem cell lines derived prior to August 9, 2001. Stem Cells Dev 13:585–597

    CAS  PubMed  Google Scholar 

  • Buzzard JJ, Gough NM, Crook JM, Colman A (2004) Karyotype of human ES cells during extended culture. Nat Biotechnol 22:381–382; author reply 382

    CAS  PubMed  Google Scholar 

  • Caspersson T, Zech L, Johansson C (1970) Analysis of human metaphase chromosome set by aid of DNA-binding fluorescent agents. Exp Cell Res 62:490–492

    CAS  PubMed  Google Scholar 

  • Catalina P, Montes R, Ligero G, Sanchez L, de la Cueva T, Bueno C, Leone PE, Menendez P (2008) Human ESCs predisposition to karyotypic instability: is a matter of culture adaptation or differential vulnerability among hESC lines due to inherent properties? Mol Cancer 7:76

    PubMed Central  PubMed  Google Scholar 

  • Cheng L, Hansen NF, Zhao L, Du Y, Zou C, Donovan FX, Chou BK, Zhou G, Li S, Dowey SN et al (2012) Low incidence of DNA sequence variation in human induced pluripotent stem cells generated by nonintegrating plasmid expression. Cell Stem Cell 10:337–344

    CAS  PubMed Central  PubMed  Google Scholar 

  • Chung TL, Turner JP, Thaker NY, Kolle G, Cooper-White JJ, Grimmond SM, Pera MF, Wolvetang EJ (2010) Ascorbate promotes epigenetic activation of CD30 in human embryonic stem cells. Stem Cells 28:1782–1793

    CAS  PubMed  Google Scholar 

  • Cohen JL, Boyer O, Klatzmann D (2001) Suicide gene therapy of graft-versus-host disease: immune reconstitution with transplanted mature T cells. Blood 98:2071–2076

    CAS  PubMed  Google Scholar 

  • Corrales NL, Mrasek K, Voigt M, Liehr T, Kosyakova N (2012) Copy number variations (CNVs) in human pluripotent cell-derived neuroprogenitors. Gene 506:377–379

    CAS  PubMed  Google Scholar 

  • Devalle S, Sartore RC, Paulsen BS, Borges HL, Martins RA, Rehen SK (2012) Implications of aneuploidy for stem cell biology and brain therapeutics. Front Cell Neurosci 6:36

    PubMed Central  PubMed  Google Scholar 

  • Diaferia GR, Conti L, Redaelli S, Cattaneo M, Mutti C, DeBlasio P, Dalpra L, Cattaneo E, Biunno I (2011) Systematic chromosomal analysis of cultured mouse neural stem cell lines. Stem Cells Dev 20:1411–1423

    CAS  PubMed  Google Scholar 

  • Draper JS, Smith K, Gokhale P, Moore HD, Maltby E, Johnson J, Meisner L, Zwaka TP, Thomson JA, Andrews PW (2004) Recurrent gain of chromosomes 17q and 12 in cultured human embryonic stem cells. Nat Biotechnol 22:53–54

    CAS  PubMed  Google Scholar 

  • Dutrillaux B, Finaz C, de Grouchy J, Lejeune J (1972) Comparison of banding patterns of human chromosomes obtained with heating, fluorescence, and proteolytic digestion. Cytogenetics 11:113–116

    CAS  PubMed  Google Scholar 

  • Elliott AM, Elliott KA, Kammesheidt A (2010) High resolution array-CGH characterization of human stem cells using a stem cell focused microarray. Mol Biotechnol 46:234–242

    CAS  PubMed  Google Scholar 

  • Eroglu A, Russo MJ, Bieganski R, Fowler A, Cheley S, Bayley H, Toner M (2000) Intracellular trehalose improves the survival of cryopreserved mammalian cells. Nat Biotechnol 18:163–167

    CAS  PubMed  Google Scholar 

  • Esteban MA, Wang T, Qin B, Yang J, Qin D, Cai J, Li W, Weng Z, Chen J, Ni S et al (2010) Vitamin C enhances the generation of mouse and human induced pluripotent stem cells. Cell Stem Cell 6:71–79

    CAS  PubMed  Google Scholar 

  • Evans MJ, Kaufman MH (1981) Establishment in culture of pluripotential cells from mouse embryos. Nature 292:154–156

    CAS  PubMed  Google Scholar 

  • Faria C, Miguens J, Antunes JL, Salgado D, Nunes S, Barroso C, Martins Mdo C, Nunes VM, Roque L (2010) Pediatric brain tumors: genetics and clinical outcome. J Neurosurg Pediatr 5:263–270

    PubMed  Google Scholar 

  • Forsyth NR, Musio A, Vezzoni P, Simpson AH, Noble BS, McWhir J (2006) Physiologic oxygen enhances human embryonic stem cell clonal recovery and reduces chromosomal abnormalities. Cloning Stem Cells 8:16–23

    CAS  PubMed  Google Scholar 

  • Fournier A, McLeer-Florin A, Lefebvre C, Duley S, Barki L, Ribeyron J, Alboukadel K, Hamaidia S, Granjon A, Gressin R et al (2010) 1q12 chromosome translocations form aberrant heterochromatic foci associated with changes in nuclear architecture and gene expression in B cell lymphoma. EMBO Mol Med 2:159–171

    PubMed Central  PubMed  Google Scholar 

  • Funk WD, Labat I, Sampathkumar J, Gourraud PA, Oksenberg JR, Rosler E, Steiger D, Sheibani N, Caillier S, Stache-Crain B et al (2012) Evaluating the genomic and sequence integrity of human ES cell lines; comparison to normal genomes. Stem Cell Res 8:154–164

    CAS  PubMed  Google Scholar 

  • Fusaki N, Ban H, Nishiyama A, Saeki K, Hasegawa M (2009) Efficient induction of transgene-free human pluripotent stem cells using a vector based on Sendai virus, an RNA virus that does not integrate into the host genome. Proc Jpn Acad Ser B Phys Biol Sci 85:348–362

    CAS  PubMed Central  PubMed  Google Scholar 

  • Goldring CE, Duffy PA, Benvenisty N, Andrews PW, Ben-David U, Eakins R, French N, Hanley NA, Kelly L, Kitteringham NR et al (2011) Assessing the safety of stem cell therapeutics. Cell Stem Cell 8:618–628

    CAS  PubMed  Google Scholar 

  • Gore A, Li Z, Fung HL, Young JE, Agarwal S, Antosiewicz-Bourget J, Canto I, Giorgetti A, Israel MA, Kiskinis E et al (2011) Somatic coding mutations in human induced pluripotent stem cells. Nature 471:63–67

    CAS  PubMed Central  PubMed  Google Scholar 

  • Gourraud PA, Gilson L, Girard M, Peschanski M (2012) The role of human leukocyte antigen matching in the development of multiethnic “haplobank” of induced pluripotent stem cell lines. Stem Cells 30:180–186

    CAS  PubMed  Google Scholar 

  • Guan XY, Xu J, Anzick SL, Zhang H, Trent JM, Meltzer PS (1996) Hybrid selection of transcribed sequences from microdissected DNA: isolation of genes within amplified region at 20q11-q13.2 in breast cancer. Cancer Res 56:3446–3450

    CAS  PubMed  Google Scholar 

  • Guo N, Puhlev I, Brown DR, Mansbridge J, Levine F (2000) Trehalose expression confers desiccation tolerance on human cells. Nat Biotechnol 18:168–171

    CAS  PubMed  Google Scholar 

  • Hanahan D, Weinberg RA (2011) Hallmarks of cancer: the next generation. Cell 144:646–674

    CAS  PubMed  Google Scholar 

  • Harrison NJ, Barnes J, Jones M, Baker D, Gokhale PJ, Andrews PW (2009) CD30 expression reveals that culture adaptation of human embryonic stem cells can occur through differing routes. Stem Cells 27:1057–1065

    CAS  PubMed Central  PubMed  Google Scholar 

  • Hayflick L (1965) The limited in vitro lifetime of human diploid cell strains. Exp Cell Res 37:614–636

    CAS  PubMed  Google Scholar 

  • Herszfeld D, Wolvetang E, Langton-Bunker E, Chung TL, Filipczyk AA, Houssami S, Jamshidi P, Koh K, Laslett AL, Michalska A et al (2006) CD30 is a survival factor and a biomarker for transformed human pluripotent stem cells. Nat Biotechnol 24:351–357

    CAS  PubMed  Google Scholar 

  • Hovatta O, Jaconi M, Tohonen V, Bena F, Gimelli S, Bosman A, Holm F, Wyder S, Zdobnov EM, Irion O et al (2010) A teratocarcinoma-like human embryonic stem cell (hESC) line and four hESC lines reveal potentially oncogenic genomic changes. PLoS One 5:e10263

    PubMed Central  PubMed  Google Scholar 

  • Hurst CD, Fiegler H, Carr P, Williams S, Carter NP, Knowles MA (2004) High-resolution analysis of genomic copy number alterations in bladder cancer by microarray-based comparative genomic hybridization. Oncogene 23:2250–2263

    CAS  PubMed  Google Scholar 

  • Hussein SM, Batada NN, Vuoristo S, Ching RW, Autio R, Narva E, Ng S, Sourour M, Hamalainen R, Olsson C, Lundin K et al (2011) Copy number variation and selection during reprogramming to pluripotency. Nature 471:58–62

    CAS  PubMed  Google Scholar 

  • Hussein SM, Elbaz J, Nagy AA (2012) Genome damage in induced pluripotent stem cells: assessing the mechanisms and their consequences. Bioessays 35:152–162

    PubMed  Google Scholar 

  • Hyka-Nouspikel N, Desmarais J, Gokhale PJ, Jones M, Meuth M, Andrews PW, Nouspikel T (2012) Deficient DNA damage response and cell cycle checkpoints lead to accumulation of point mutations in human embryonic stem cells. Stem Cells 30:1901–1910

    CAS  PubMed  Google Scholar 

  • Imreh MP, Gertow K, Cedervall J, Unger C, Holmberg K, Szoke K, Csoregh L, Fried G, Dilber S, Blennow E, Ahrlund-Richter L (2006) In vitro culture conditions favoring selection of chromosomal abnormalities in human ES cells. J Cell Biochem 99:508–516

    CAS  PubMed  Google Scholar 

  • Inzunza J, Sahlen S, Holmberg K, Stromberg AM, Teerijoki H, Blennow E, Hovatta O, Malmgren H (2004) 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

    CAS  PubMed  Google Scholar 

  • ISCI (2009) Consensus guidance for banking and supply of human embryonic stem cell lines for research purposes. Stem Cell Rev 5:301–314

    Google Scholar 

  • Ji J, Ng SH, Sharma V, Neculai D, Hussein S, Sam M, Trinh Q, Church GM, McPherson JD, Nagy A, Batada NN (2012) Elevated coding mutation rate during the reprogramming of human somatic cells into induced pluripotent stem cells. Stem Cells 30:435–440

    CAS  PubMed  Google Scholar 

  • Josephson R, Sykes G, Liu Y, Ording C, Xu W, Zeng X, Shin S, Loring J, Maitra A, Rao MS, Auerbach JM (2006) A molecular scheme for improved characterization of human embryonic stem cell lines. BMC Biol 4:28

    PubMed Central  PubMed  Google Scholar 

  • Kaji K, Norrby K, Paca A, Mileikovsky M, Mohseni P, Woltjen K (2009) Virus-free induction of pluripotency and subsequent excision of reprogramming factors. Nature 458:771–775

    CAS  PubMed Central  PubMed  Google Scholar 

  • Kano H, Godoy I, Courtney C, Vetter MR, Gerton GL, Ostertag EM, Kazazian HH Jr (2009) L1 retrotransposition occurs mainly in embryogenesis and creates somatic mosaicism. Genes Dev 23:1303–1312

    CAS  PubMed  Google Scholar 

  • Kim D, Kim CH, Moon JI, Chung YG, Chang MY, Han BS, Ko S, Yang E, Cha KY, Lanza R, Kim KS (2009) Generation of human induced pluripotent stem cells by direct delivery of reprogramming proteins. Cell Stem Cell 4:472–476

    CAS  PubMed Central  PubMed  Google Scholar 

  • Koch P, Opitz T, Steinbeck JA, Ladewig J, Brustle O (2009) A rosette-type, self-renewing human ES cell-derived neural stem cell with potential for in vitro instruction and synaptic integration. Proc Natl Acad Sci U S A 106:3225–3230

    CAS  PubMed Central  PubMed  Google Scholar 

  • Kondrashov AS (2003) Direct estimates of human per nucleotide mutation rates at 20 loci causing Mendelian diseases. Hum Mutat 21:12–27

    CAS  PubMed  Google Scholar 

  • Koynova DK, Jordanova ES, Milev AD, Dijkman R, Kirov KS, Toncheva DI, Gruis NA (2007) Gene-specific fluorescence in-situ hybridization analysis on tissue microarray to refine the region of chromosome 20q amplification in melanoma. Melanoma Res 17:37–41

    CAS  PubMed  Google Scholar 

  • Kuick RD, Neel JV, Strahler JR, Chu EH, Bargal R, Fox DA, Hanash SM (1992) Similarity of spontaneous germinal and in vitro somatic cell mutation rates in humans: implications for carcinogenesis and for the role of exogenous factors in “spontaneous” germinal mutagenesis. Proc Natl Acad Sci U S A 89:7036–7040

    CAS  PubMed Central  PubMed  Google Scholar 

  • Lafaille FG, Pessach IM, Zhang SY, Ciancanelli MJ, Herman M, Abhyankar A, Ying SW, Keros S, Goldstein PA, Mostoslavsky G et al (2012) Impaired intrinsic immunity to HSV-1 in human iPSC-derived TLR3-deficient CNS cells. Nature 491:769–773

    CAS  PubMed Central  PubMed  Google Scholar 

  • Lagarkova MA, Volchkov PY, Philonenko ES, Pfannkuche K, Prokhorovich MA, Zabotina T, Hescheler J, Kiselev SL (2008) CD 30 is a marker of undifferentiated human embryonic stem cells rather than a biomarker of transformed hESCs. Cell Cycle 7:3610–3612

    CAS  PubMed  Google Scholar 

  • Laurent LC, Ulitsky I, Slavin I, Tran H, Schork A, Morey R, Lynch C, Harness JV, Lee S, Barrero MJ et al (2011) 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 8:106–118

    CAS  PubMed Central  PubMed  Google Scholar 

  • Lefort N, Feyeux M, Bas C, Feraud O, Bennaceur-Griscelli A, Tachdjian G, Peschanski M, Perrier AL (2008) Human embryonic stem cells reveal recurrent genomic instability at 20q11.21. Nat Biotechnol 26:1364–1366

    CAS  PubMed  Google Scholar 

  • Lefort N, Perrier AL, Laabi Y, Varela C, Peschanski M (2009) Human embryonic stem cells and genomic instability. Regen Med 4:899–909

    PubMed  Google Scholar 

  • Li TS, Marban E (2010) Physiological levels of reactive oxygen species are required to maintain genomic stability in stem cells. Stem Cells 28:1178–1185

    CAS  PubMed Central  PubMed  Google Scholar 

  • Loh YH, Agarwal S, Park IH, Urbach A, Huo H, Heffner GC, Kim K, Miller JD, Ng K, Daley GQ (2009) Generation of induced pluripotent stem cells from human blood. Blood 113:5476–5479

    CAS  PubMed  Google Scholar 

  • Lund RJ, Narva E, Lahesmaa R (2012a) Genetic and epigenetic stability of human pluripotent stem cells. Nat Rev Genet 13:732–744

    CAS  PubMed  Google Scholar 

  • Lund RJ, Nikula T, Rahkonen N, Narva E, Baker D, Harrison N, Andrews P, Otonkoski T, Lahesmaa R (2012b) High-throughput karyotyping of human pluripotent stem cells. Stem Cell Res 9:192–195

    CAS  PubMed Central  PubMed  Google Scholar 

  • Maitra A, Arking DE, Shivapurkar N, Ikeda M, Stastny V, Kassauei K, Sui G, Cutler DJ, Liu Y, Brimble SN et al (2005) Genomic alterations in cultured human embryonic stem cells. Nat Genet 37:1099–1103

    CAS  PubMed  Google Scholar 

  • Martin GR (1981) Isolation of a pluripotent cell line from early mouse embryos cultured in medium conditioned by teratocarcinoma stem cells. Proc Natl Acad Sci U S A 78:7634–7638

    CAS  PubMed Central  PubMed  Google Scholar 

  • Martins-Taylor K, Xu RH (2012) Concise review: genomic stability of human induced pluripotent stem cells. Stem Cells 30:22–27

    CAS  PubMed  Google Scholar 

  • Martins-Taylor K, Nisler BS, Taapken SM, Compton T, Crandall L, Montgomery KD, Lalande M, Xu RH (2011) Recurrent copy number variations in human induced pluripotent stem cells. Nat Biotechnol 29:488–491

    CAS  PubMed  Google Scholar 

  • Mateizel I, Spits C, Verloes A, Mertzanidou A, Liebaers I, Sermon K (2009) Characterization of CD30 expression in human embryonic stem cell lines cultured in serum-free media and passaged mechanically. Hum Reprod 24:2477–2489

    CAS  PubMed  Google Scholar 

  • Mayshar Y, Ben-David U, Lavon N, Biancotti JC, Yakir B, Clark AT, Plath K, Lowry WE, Benvenisty N (2010) Identification and classification of chromosomal aberrations in human induced pluripotent stem cells. Cell Stem Cell 7:521–531

    CAS  PubMed  Google Scholar 

  • Midorikawa Y, Yamamoto S, Ishikawa S, Kamimura N, Igarashi H, Sugimura H, Makuuchi M, Aburatani H (2006) Molecular karyotyping of human hepatocellular carcinoma using single-nucleotide polymorphism arrays. Oncogene 25:5581–5590

    CAS  PubMed  Google Scholar 

  • Mitalipova MM, Rao RR, Hoyer DM, Johnson JA, Meisner LF, Jones KL, Dalton S, Stice SL (2005) Preserving the genetic integrity of human embryonic stem cells. Nat Biotechnol 23:19–20

    CAS  PubMed  Google Scholar 

  • Munoz-Lopez M, Garcia-Canadas M, Macia A, Morell S, Garcia-Perez JL (2012) Analysis of LINE-1 expression in human pluripotent cells. Methods Mol Biol 873:113–125

    CAS  PubMed  Google Scholar 

  • Nachman MW, Crowell SL (2000) Estimate of the mutation rate per nucleotide in humans. Genetics 156:297–304

    CAS  PubMed  Google Scholar 

  • Narva E, Autio R, Rahkonen N, Kong L, Harrison N, Kitsberg D, Borghese L, Itskovitz-Eldor J, Rasool O, Dvorak P et al (2010) 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

    PubMed  Google Scholar 

  • Nemati S, Hatami M, Kiani S, Hemmesi K, Gourabi H, Masoudi N, Alaei S, Baharvand H (2011) Long-term self-renewable feeder-free human induced pluripotent stem cell-derived neural progenitors. Stem Cells Dev 20:503–514

    CAS  PubMed  Google Scholar 

  • Nguyen HT, Geens M, Spits C (2013) Genetic and epigenetic instability in human pluripotent stem cells. Hum Reprod Update 19:187–205

    CAS  PubMed  Google Scholar 

  • Nouspikel T (2007) DNA repair in differentiated cells: some new answers to old questions. Neuroscience 145:1213–1221

    CAS  PubMed  Google Scholar 

  • Nouspikel T (2008) Nucleotide excision repair and neurological diseases. DNA Repair (Amst) 7:1155–1167

    CAS  Google Scholar 

  • Okita K, Yamakawa T, Matsumura Y, Sato Y, Amano N, Watanabe A, Goshima N, Yamanaka S (2013) An efficient nonviral method to generate integration-free human-induced pluripotent stem cells from cord blood and peripheral blood cells. Stem Cells 31:458–466

    CAS  PubMed  Google Scholar 

  • Olariu V, Harrison NJ, Coca D, Gokhale PJ, Baker D, Billings S, Kadirkamanathan V, Andrews PW (2010) Modeling the evolution of culture-adapted human embryonic stem cells. Stem Cell Res 4:50–56

    PubMed  Google Scholar 

  • Oliveira PH, Boura JS, Abecasis MM, Gimble JM, da Silva CL, Cabral JM (2012) Impact of hypoxia and long-term cultivation on the genomic stability and mitochondrial performance of ex vivo expanded human stem/stromal cells. Stem Cell Res 9:225–236

    CAS  PubMed  Google Scholar 

  • Prigione A, Hossini AM, Lichtner B, Serin A, Fauler B, Megges M, Lurz R, Lehrach H, Makrantonaki E, Zouboulis CC, Adjaye J (2011a) Mitochondrial-associated cell death mechanisms are reset to an embryonic-like state in aged donor-derived iPS cells harboring chromosomal aberrations. PLoS One 6:e27352

    CAS  PubMed Central  PubMed  Google Scholar 

  • Prigione A, Lichtner B, Kuhl H, Struys EA, Wamelink M, Lehrach H, Ralser M, Timmermann B, Adjaye J (2011b) Human induced pluripotent stem cells harbor homoplasmic and heteroplasmic mitochondrial DNA mutations while maintaining human embryonic stem cell-like metabolic reprogramming. Stem Cells 29:1338–1348

    CAS  PubMed  Google Scholar 

  • Ronen D, Benvenisty N (2012) Genomic stability in reprogramming. Curr Opin Genet Dev 22:444–449

    CAS  PubMed  Google Scholar 

  • Ruiz S, Gore A, Li Z, Panopoulos AD, Montserrat N, Fung HL, Giorgetti A, Bilic J, Batchelder EM, Zaehres H et al (2013) Analysis of protein-coding mutations in hiPSCs and their possible role during somatic cell reprogramming. Nat Commun 4:1382

    PubMed  Google Scholar 

  • Sareen D, McMillan E, Ebert AD, Shelley BC, Johnson JA, Meisner LF, Svendsen CN (2009) Chromosome 7 and 19 trisomy in cultured human neural progenitor cells. PLoS One 4:e7630

    PubMed Central  PubMed  Google Scholar 

  • Schrock E, du Manoir S, Veldman T, Schoell B, Wienberg J, Ferguson-Smith MA, Ning Y, Ledbetter DH, Bar-Am I, Soenksen D et al (1996) Multicolor spectral karyotyping of human chromosomes. Science 273:494–497

    CAS  PubMed  Google Scholar 

  • Schwartz SD, Hubschman JP, Heilwell G, Franco-Cardenas V, Pan CK, Ostrick RM, Mickunas E, Gay R, Klimanskaya I, Lanza R (2012) Embryonic stem cell trials for macular degeneration: a preliminary report. Lancet 379:713–720

    CAS  PubMed  Google Scholar 

  • Scotto L, Narayan G, Nandula SV, Arias-Pulido H, Subramaniyam S, Schneider A, Kaufmann AM, Wright JD, Pothuri B, Mansukhani M, Murty VV (2008) Identification of copy number gain and overexpressed genes on chromosome arm 20q by an integrative genomic approach in cervical cancer: potential role in progression. Genes Chromosomes Cancer 47:755–765

    CAS  PubMed  Google Scholar 

  • Seabright M (1971) A rapid banding technique for human chromosomes. Lancet 2:971–972

    CAS  PubMed  Google Scholar 

  • Soldner F, Hockemeyer D, Beard C, Gao Q, Bell GW, Cook EG, Hargus G, Blak A, Cooper O, Mitalipova M et al (2009) Parkinson’s disease patient-derived induced pluripotent stem cells free of viral reprogramming factors. Cell 136:964–977

    CAS  PubMed Central  PubMed  Google Scholar 

  • Spits C, Mateizel I, Geens M, Mertzanidou A, Staessen C, Vandeskelde Y, Van der Elst J, Liebaers I, Sermon K (2008) Recurrent chromosomal abnormalities in human embryonic stem cells. Nat Biotechnol 26:1361–1363

    CAS  PubMed  Google Scholar 

  • Stadtfeld M, Nagaya M, Utikal J, Weir G, Hochedlinger K (2008) Induced pluripotent stem cells generated without viral integration. Science 322:945–949

    CAS  PubMed  Google Scholar 

  • Stephenson E, Ogilvie CM, Patel H, Cornwell G, Jacquet L, Kadeva N, Braude P, Ilic D (2010) Safety paradigm: genetic evaluation of therapeutic grade human embryonic stem cells. J R Soc Interface 7(Suppl 6):S677–S688

    PubMed Central  PubMed  Google Scholar 

  • Symer DE, Connelly C, Szak ST, Caputo EM, Cost GJ, Parmigiani G, Boeke JD (2002) Human l1 retrotransposition is associated with genetic instability in vivo. Cell 110:327–338

    CAS  PubMed  Google Scholar 

  • Taapken SM, Nisler BS, Newton MA, Sampsell-Barron TL, Leonhard KA, McIntire EM, Montgomery KD (2011) Karotypic abnormalities in human induced pluripotent stem cells and embryonic stem cells. Nat Biotechnol 29:313–314

    CAS  PubMed  Google Scholar 

  • Takahashi K, Yamanaka S (2006) Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors. Cell 126:663–676

    CAS  PubMed  Google Scholar 

  • Takahashi K, Tanabe K, Ohnuki M, Narita M, Ichisaka T, Tomoda K, Yamanaka S (2007) Induction of pluripotent stem cells from adult human fibroblasts by defined factors. Cell 131:861–872

    CAS  PubMed  Google Scholar 

  • Tanner MM, Tirkkonen M, Kallioniemi A, Isola J, Kuukasjarvi T, Collins C, Kowbel D, Guan XY, Trent J, Gray JW, Meltzer P, Kallioniemi OP (1996) Independent amplification and frequent co-amplification of three nonsyntenic regions on the long arm of chromosome 20 in human breast cancer. Cancer Res 56:3441–3445

    CAS  PubMed  Google Scholar 

  • Thomson JA, Itskovitz-Eldor J, Shapiro SS, Waknitz MA, Swiergiel JJ, Marshall VS, Jones JM (1998) Embryonic stem cell lines derived from human blastocysts. Science 282:1145–1147

    CAS  PubMed  Google Scholar 

  • Thomson A, Wojtacha D, Hewitt Z, Priddle H, Sottile V, Di Domenico A, Fletcher J, Waterfall M, Corrales NL, Ansell R, McWhir J (2008) Human embryonic stem cells passaged using enzymatic methods retain a normal karyotype and express CD30. Cloning Stem Cells 10:89–106

    CAS  PubMed  Google Scholar 

  • Tonon G, Wong KK, Maulik G, Brennan C, Feng B, Zhang Y, Khatry DB, Protopopov A, You MJ, Aguirre AJ et al (2005) High-resolution genomic profiles of human lung cancer. Proc Natl Acad Sci U S A 102:9625–9630

    CAS  PubMed Central  PubMed  Google Scholar 

  • Utikal J, Maherali N, Kulalert W, Hochedlinger K (2009) Sox2 is dispensable for the reprogramming of melanocytes and melanoma cells into induced pluripotent stem cells. J Cell Sci 122:3502–3510

    CAS  PubMed  Google Scholar 

  • Van Haute L, Spits C, Geens M, Seneca S, Sermon K (2013) Human embryonic stem cells commonly display large mitochondrial DNA deletions. Nat Biotechnol 31:20–23

    PubMed  Google Scholar 

  • Varela C, Denis JA, Polentes J, Feyeux M, Aubert S, Champon B, Pietu G, Peschanski M, Lefort N (2012) Recurrent genomic instability of chromosome 1q in neural derivatives of human embryonic stem cells. J Clin Invest 122:569–574

    CAS  PubMed Central  PubMed  Google Scholar 

  • Werbowetski-Ogilvie TE, Bosse M, Stewart M, Schnerch A, Ramos-Mejia V, Rouleau A, Wynder T, Smith MJ, Dingwall S, Carter T et al (2009) Characterization of human embryonic stem cells with features of neoplastic progression. Nat Biotechnol 27:91–97

    CAS  PubMed  Google Scholar 

  • Wissing S, Munoz-Lopez M, Macia A, Yang Z, Montano M, Collins W, Garcia-Perez JL, Moran JV, Greene WC (2012) Reprogramming somatic cells into iPS cells activates LINE-1 retroelement mobility. Hum Mol Genet 21:208–218

    PubMed  Google Scholar 

  • Woltjen K, Michael IP, Mohseni P, Desai R, Mileikovsky M, Hamalainen R, Cowling R, Wang W, Liu P, Gertsenstein M et al (2009) piggyBac transposition reprograms fibroblasts to induced pluripotent stem cells. Nature 458:766–770

    CAS  PubMed Central  PubMed  Google Scholar 

  • Wu H, Kim KJ, Mehta K, Paxia S, Sundstrom A, Anantharaman T, Kuraishy AI, Doan T, Ghosh J, Pyle AD et al (2008) Copy number variant analysis of human embryonic stem cells. Stem Cells 26:1484–1489

    CAS  PubMed Central  PubMed  Google Scholar 

  • Yakubov E, Rechavi G, Rozenblatt S, Givol D (2010) Reprogramming of human fibroblasts to pluripotent stem cells using mRNA of four transcription factors. Biochem Biophys Res Commun 394:189–193

    CAS  PubMed  Google Scholar 

  • Yang Y, Geldmacher DS, Herrup K (2001) DNA replication precedes neuronal cell death in Alzheimer’s disease. J Neurosci 21:2661–2668

    CAS  PubMed  Google Scholar 

  • Young MA, Larson DE, Sun CW, George DR, Ding L, Miller CA, Lin L, Pawlik KM, Chen K et al (2012) Background mutations in parental cells account for most of the genetic heterogeneity of induced pluripotent stem cells. Cell Stem Cell 10:570–582

    CAS  PubMed Central  PubMed  Google Scholar 

  • Yu J, Vodyanik MA, Smuga-Otto K, Antosiewicz-Bourget J, Frane JL, Tian S, Nie J, Jonsdottir GA, Ruotti V, Stewart R et al (2007) Induced pluripotent stem cell lines derived from human somatic cells. Science 318:1917–1920

    CAS  PubMed  Google Scholar 

  • Yurov YB, Iourov IY, Vorsanova SG, Liehr T, Kolotii AD, Kutsev SI, Pellestor F, Beresheva AK, Demidova IA, Kravets VS et al (2007) Aneuploidy and confined chromosomal mosaicism in the developing human brain. PLoS One 2:e558

    PubMed Central  PubMed  Google Scholar 

  • Yurov YB, Vorsanova SG, Iourov IY (2009) GIN'n'CIN hypothesis of brain aging: deciphering the role of somatic genetic instabilities and neural aneuploidy during ontogeny. Mol Cytogenet 2:23

    PubMed Central  PubMed  Google Scholar 

  • Zhou H, Wu S, Joo JY, Zhu S, Han DW, Lin T, Trauger S, Bien G, Yao S, Zhu Y et al (2009) Generation of induced pluripotent stem cells using recombinant proteins. Cell Stem Cell 4:381–384

    CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. French Institute of Health and Medical Research, UMR 861, I-Stem, French Muscular Dystrophy Association, Institute for Stem Cell Therapy and Exploration of Monogenic Diseases, University of Évry Val d’Essonne, Evry cedex, France

    Nathalie Lefort & Marc Peschanski

Authors
  1. Nathalie Lefort
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Marc Peschanski
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding authors

Correspondence to Nathalie Lefort or Marc Peschanski .

Editor information

Editors and Affiliations

  1. French Institute of Health and Medical Research U1130, French National Center for Scientific Research, Pierre-and-Marie-Curie University, Paris, France

    Marie-Pierre Junier

  2. Departments of Pediatrics and Pathology & Cell Biology, Columbia University College of Physicians and Surgeons, New York, New York, USA

    Steven G. Kernie

Rights and permissions

Reprints and permissions

Copyright information

© 2014 Springer Science+Business Media New York

About this chapter

Cite this chapter

Lefort, N., Peschanski, M. (2014). Genomic Integrity of Embryonic and Neural Stem Cells. In: Junier, MP., Kernie, S. (eds) Endogenous Stem Cell-Based Brain Remodeling in Mammals. Stem Cell Biology and Regenerative Medicine. Springer, Boston, MA. https://doi.org/10.1007/978-1-4899-7399-3_9

Download citation

Publish with us

Policies and ethics

Search

Navigation