Rett Syndrome and Stem Cell Research

  • Keita TsujimuraEmail author
  • Kinichi NakashimaEmail author


Rett syndrome (RTT) is a devastating neurodevelopmental disorder resulting from mutations in the X-linked gene encoding methyl-CpG-binding protein 2 (MECP2). MECP2 mutations are also associated with other neurodevelopmental diseases, including autism and schizophrenia. Therefore, elucidating the mechanism of RTT can contribute to understanding the pathogenesis of a wide range of neurodevelopmental diseases. Despite its importance, however, the RTT pathogenesis remains unclear, and effective therapeutic treatment has not been developed. Offering an opportunity to move toward this goal, however, is the recent advance in the stem cell research field of the development of induced pluripotent stem cell (iPSC) technology. This technology can yield important insights into disease pathophysiology and has the potential to provide disease models for screening new drugs. Here, we discuss applications of recent stem cell technology to the field of research on RTT and describe the stem cell biology of RTT pathogenesis.


MeCP2 Rett syndrome Neurodevelopmental disorders Induced pluripotent stem cells (iPSCs) Neural stem cells (NSCs) 



This study was in part supported by JSPS KAKENHI Grant Number 16 K18391 to K.T. and MEXT KAKENHI Grant Number 17H01390 to K.N., Foundation of Synapse and Neurocircuit Pathology, and Intramural Research Grant 27-7 for Neurological and Psychiatric Disorders of the National Center of Neurology and Psychiatry. We thank Elizabeth Nakajima for critical reading of the manuscript.


  1. 1.
    Amir RE, Van den Veyver IB, Wan M, Tran CQ, Francke U, Zoghbi HY (1999) Rett syndrome is caused by mutations in X-linked MECP2, encoding methyl-CpG-binding protein 2. Nat Genet 23:185–188CrossRefPubMedGoogle Scholar
  2. 2.
    Ananiev G, Williams EC, Li H, Chang Q (2011) Isogenic pairs of wild type and mutant induced pluripotent stem cell (iPSC) lines from Rett syndrome patients as in vitro disease model. PLoS One 6:e25255CrossRefPubMedPubMedCentralGoogle Scholar
  3. 3.
    Andoh-Noda T, Akamatsu W, Miyake K, Matsumoto T, Yamaguchi R, Sanosaka T et al (2015) Differentiation of multipotent neural stem cells derived from Rett syndrome patients is biased toward the astrocytic lineage. Mol Brain 8:31CrossRefPubMedPubMedCentralGoogle Scholar
  4. 4.
    Armstrong D, Dunn JK, Antalffy B, Trivedi R (1995) Selective dendritic alterations in the cortex of Rett syndrome. J Neuropathol Exp Neurol 54:195–201CrossRefPubMedGoogle Scholar
  5. 5.
    Baker SA, Chen L, Wilkins AD, Yu P, Lichtarge O, Zoghbi HY (2013) An AT-hook domain in MeCP2 determines the clinical course of Rett syndrome and related disorders. Cell 152:984–996CrossRefPubMedPubMedCentralGoogle Scholar
  6. 6.
    Bienvenu T, Chelly J (2006) Molecular genetics of Rett syndrome: when DNA methylation goes unrecognized. Nat Rev Genet 7:415–426CrossRefPubMedGoogle Scholar
  7. 7.
    Brero A, Easwaran HP, Nowak D, Grunewald I, Cremer T, Leonhardt H et al (2005) Methyl CpG-binding proteins induce large-scale chromatin reorganization during terminal differentiation. J Cell Biol 169:733–743CrossRefPubMedPubMedCentralGoogle Scholar
  8. 8.
    Chahrour M, Jung SY, Shaw C, Zhou X, Wong ST, Qin J et al (2008) MeCP2, a key contributor to neurological disease activates and represses transcription. Science 320:1224–1229CrossRefPubMedPubMedCentralGoogle Scholar
  9. 9.
    Chahrour M, Zoghbi HY (2007) The story of Rett syndrome: from clinic to neurobiology. Neuron 56:422–437CrossRefPubMedGoogle Scholar
  10. 10.
    Chao HT, Chen H, Samaco RC, Xue M, Chahrour M, Yoo J et al (2010) Dysfunction in GABA signalling mediates autism-like stereotypies and Rett syndrome phenotypes. Nature 468:263–269CrossRefPubMedPubMedCentralGoogle Scholar
  11. 11.
    Chen RZ, Akbarian S, Tudor M, Jaenisch R (2001) Deficiency of methyl-CpG binding protein-2 in CNS neurons results in a Rett-like phenotype in mice. Nat Genet 27:327–331CrossRefPubMedGoogle Scholar
  12. 12.
    Chen Y, Yu J, Niu Y, Qin D, Liu H, Li G et al (2017) Modeling Rett syndrome using TALEN-edited MECP2 mutant cynomolgus monkeys. Cell 169:945–955CrossRefPubMedPubMedCentralGoogle Scholar
  13. 13.
    Cheng TL, Wang Z, Liao Q, Zhu Y, Zhou WH, Xu W et al (2014) MeCP2 suppresses nuclear microRNA processing and dendritic growth by regulating the DGCR8/Drosha complex. Dev Cell 28:547–560CrossRefPubMedGoogle Scholar
  14. 14.
    Cheung AY, Horvath LM, Grafodatskaya D, Pasceri P, Weksberg R, Hotta A et al (2011) Isolation of MECP2-null Rett syndrome patient hiPS cells and isogenic controls through X-chromosome inactivation. Hum Mol Genet 20:2103–2115CrossRefPubMedPubMedCentralGoogle Scholar
  15. 15.
    Christian M, Cermak T, Doyle EL, Schmidt C, Zhang F, Hummel A et al (2010) Targeting DNA double-strand breaks with TAL effector nucleases. Genetics 186:757–761CrossRefPubMedPubMedCentralGoogle Scholar
  16. 16.
    Christodoulou J, Grimm A, Maher T, Bennetts B (2003) RettBASE: the IRSA MECP2 variation database-a new mutation database in evolution. Hum Mutat 21:466–472CrossRefPubMedGoogle Scholar
  17. 17.
    Colantuoni C, Jeon OH, Hyder K, Chenchik A, Khimani AH, Narayanan V et al (2001) Gene expression profiling in postmortem Rett syndrome brain: differential gene expression and patient classification. Neurobiol Dis 8:847–865CrossRefPubMedGoogle Scholar
  18. 18.
    Cong L, Ran FA, Cox D, Lin S, Barretto R, Habib N et al (2013) Multiplex genome engineering using CRISPR-Cas systems. Science 339:819–823CrossRefPubMedPubMedCentralGoogle Scholar
  19. 19.
    Cronk JC, Derecki NC, Ji E, Xu Y, Lampano AE, Smirnov I et al (2015) Methyl-CpG binding protein 2 regulates microglia and macrophage gene expression in response to inflammatory stimuli. Immunity 42:679–691CrossRefPubMedPubMedCentralGoogle Scholar
  20. 20.
    Dragich JM, Kim YH, Arnold AP, Schanen NC (2007) Differential distribution of the MeCP2 splice variants in the postnatal mouse brain. J Comp Neurol 501:526–542CrossRefPubMedGoogle Scholar
  21. 21.
    Dutta D, Heo I, Clevers H (2017) Disease modeling in stem cell-derived 3D organoid systems. Trends Mol Med 23:393–410CrossRefPubMedGoogle Scholar
  22. 22.
    Ernst C (2016) Proliferation and differentiation deficits are a major convergence point for neurodevelopmental disorders. Trends Neurosci 39:290–299CrossRefPubMedGoogle Scholar
  23. 23.
    Fukuda T, Itoh M, Ichikawa T, Washiyama K, Goto Y (2005) Delayed maturation of neuronal architecture and synaptogenesis in cerebral cortex of Mecp2-deficient mice. J Neuropathol Exp Neurol 64:537–544CrossRefPubMedGoogle Scholar
  24. 24.
    Fyffe SL, Neul JL, Samaco RC, Chao HT, Ben-Shachar S, Moretti P et al (2008) Deletion of Mecp2 in Sim1-expressing neurons reveals a critical role for MeCP2 in feeding behavior, aggression, and the response to stress. Neuron 59:947–958CrossRefPubMedPubMedCentralGoogle Scholar
  25. 25.
    Gemelli T, Berton O, Nelson ED, Perrotti LI, Jaenisch R, Monteggia LM (2006) Postnatal loss of methyl-CpG binding protein 2 in the forebrain is sufficient to mediate behavioral aspects of Rett syndrome in mice. Biol Psychiatry 59:468–476CrossRefPubMedGoogle Scholar
  26. 26.
    Giacometti E, Luikenhuis S, Beard C, Jaenisch R (2007) Partial rescue of MeCP2 deficiency by postnatal activation of MeCP2. Proc Natl Acad Sci U S A 104:1931–1936CrossRefPubMedPubMedCentralGoogle Scholar
  27. 27.
    Guy J, Hendrich B, Holmes M, Martin JE, Bird A (2001) A mouse Mecp2-null mutation causes neurological symptoms that mimic Rett syndrome. Nat Genet 27:322–326CrossRefPubMedGoogle Scholar
  28. 28.
    Harikrishnan KN, Chow MZ, Baker EK, Pal S, Bassal S, Brasacchio D et al (2005) Brahma links the SWI/SNF chromatin-remodeling complex with MeCP2-dependent transcriptional silencing. Nat Genet 37:254–264CrossRefPubMedGoogle Scholar
  29. 29.
    Heckman LD, Chahrour MH, Zoghbi HY (2014) Rett-causing mutations reveal two domains critical for MeCP2 function and for toxicity in MECP2 duplication syndrome mice. Elife 3:e02676CrossRefPubMedCentralGoogle Scholar
  30. 30.
    Hendrich B, Bird A (1998) Identification and characterization of a family of mammalian methyl-CpG binding proteins. Mol Cell Biol 18:6538–6547CrossRefPubMedPubMedCentralGoogle Scholar
  31. 31.
    Hockemeyer D, Soldner F, Beard C, Gao Q, Mitalipova M, DeKelver RC et al (2009) Efficient targeting of expressed and silent genes in human ESCs and iPSCs using zinc-finger nucleases. Nat Biotechnol 27:851–857CrossRefPubMedPubMedCentralGoogle Scholar
  32. 32.
    Hockemeyer D, Wang H, Kiani S, Lai CS, Gao Q, Cassady JP et al (2011) Genetic engineering of human pluripotent cells using TALE nucleases. Nat Biotechnol 29:731–734CrossRefPubMedPubMedCentralGoogle Scholar
  33. 33.
    Hotta A, Cheung AY, Farra N, Vijayaragavan K, Seguin CA, Draper JS et al (2009) Isolation of human iPS cells using EOS lentiviral vectors to select for pluripotency. Nat Methods 6:370–376CrossRefPubMedGoogle Scholar
  34. 34.
    Jellinger K, Armstrong D, Zoghbi HY, Percy AK (1988) Neuropathology of Rett syndrome. Acta Neuropathol 76:142–158CrossRefPubMedGoogle Scholar
  35. 35.
    Jinek M, Chylinski K, Fonfara I, Hauer M, Doudna JA, Charpentier E (2012) A programmable dual-RNA-guided DNA endonuclease in adaptive bacterial immunity. Science 337:816–821CrossRefGoogle Scholar
  36. 36.
    Jo J, Xiao Y, Sun AX, Cukuroglu E, Tran HD, Goke J et al (2016) Midbrain-like organoids from human pluripotent stem cells contain functional dopaminergic and neuromelanin-producing neurons. Cell Stem Cell 19:248–257CrossRefPubMedPubMedCentralGoogle Scholar
  37. 37.
    Jones PL, Veenstra GJ, Wade PA, Vermaak D, Kass SU, Landsberger N et al (1998) Methylated DNA and MeCP2 recruit histone deacetylase to repress transcription. Nat Genet 19:187–191CrossRefPubMedGoogle Scholar
  38. 38.
    Kerr B, Soto CJ, Saez M, Abrams A, Walz K, Young JI (2012) Transgenic complementation of MeCP2 deficiency: phenotypic rescue of Mecp2-null mice by isoform-specific transgenes. Eur J Hum Genet 20:69–76CrossRefPubMedGoogle Scholar
  39. 39.
    Kim KY, Hysolli E, Park IH (2011) Neuronal maturation defect in induced pluripotent stem cells from patients with Rett syndrome. Proc Natl Acad Sci U S A 108:14169–14174CrossRefPubMedPubMedCentralGoogle Scholar
  40. 40.
    Kishi N, Macklis JD (2004) MECP2 is progressively expressed in post-migratory neurons and is involved in neuronal maturation rather than cell fate decisions. Mol Cell Neurosci 27:306–321CrossRefPubMedGoogle Scholar
  41. 41.
    Kohyama J, Kojima T, Takatsuka E, Yamashita T, Namiki J, Hsieh J et al (2008) Epigenetic regulation of neural cell differentiation plasticity in the adult mammalian brain. Proc Natl Acad Sci U S A 105:18012–18017CrossRefPubMedPubMedCentralGoogle Scholar
  42. 42.
    Kriaucionis S, Bird A (2004) The major form of MeCP2 has a novel N-terminus generated by alternative splicing. Nucleic Acids Res 32:1818–1823CrossRefPubMedPubMedCentralGoogle Scholar
  43. 43.
    Lancaster MA, Renner M, Martin CA, Wenzel D, Bicknell LS, Hurles ME et al (2013) Cerebral organoids model human brain development and microcephaly. Nature 501:373–379CrossRefPubMedGoogle Scholar
  44. 44.
    Li H, Zhong X, Chau KF, Santistevan NJ, Guo W, Kong G et al (2014) Cell cycle-linked MeCP2 phosphorylation modulates adult neurogenesis involving the Notch signalling pathway. Nat Commun 5:5601CrossRefPubMedPubMedCentralGoogle Scholar
  45. 45.
    Li Y, Wang H, Muffat J, Cheng AW, Orlando DA, Loven J et al (2013) Global transcriptional and translational repression in human-embryonic-stem-cell-derived Rett syndrome neurons. Cell Stem Cell 13:446–458CrossRefPubMedPubMedCentralGoogle Scholar
  46. 46.
    Lioy DT, Garg SK, Monaghan CE, Raber J, Foust KD, Kaspar BK et al (2011) A role for glia in the progression of Rett’s syndrome. Nature 475:497–500CrossRefPubMedPubMedCentralGoogle Scholar
  47. 47.
    Liu H, Chen Y, Niu Y, Zhang K, Kang Y, Ge W et al (2014) TALEN-mediated gene mutagenesis in rhesus and cynomolgus monkeys. Cell Stem Cell 14:323–328CrossRefPubMedPubMedCentralGoogle Scholar
  48. 48.
    Luikenhuis S, Giacometti E, Beard CF, Jaenisch R (2004) Expression of MeCP2 in postmitotic neurons rescues Rett syndrome in mice. Proc Natl Acad Sci U S A 101:6033–6038CrossRefPubMedPubMedCentralGoogle Scholar
  49. 49.
    Lyst MJ, Ekiert R, Ebert DH, Merusi C, Nowak J, Selfridge J et al (2013) Rett syndrome mutations abolish the interaction of MeCP2 with the NCoR/SMRT co-repressor. Nat Neurosci 16:898–902CrossRefPubMedGoogle Scholar
  50. 50.
    Marchetto MC, Carromeu C, Acab A, Yu D, Yeo GW, Mu Y et al (2010) A model for neural development and treatment of Rett syndrome using human induced pluripotent stem cells. Cell 143:527–539CrossRefPubMedPubMedCentralGoogle Scholar
  51. 51.
    Mariani J, Coppola G, Zhang P, Abyzov A, Provini L, Tomasini L et al (2015) FOXG1-dependent dysregulation of GABA/glutamate neuron differentiation in autism spectrum disorders. Cell 162:375–390CrossRefPubMedPubMedCentralGoogle Scholar
  52. 52.
    Maunakea AK, Chepelev I, Cui K, Zhao K (2013) Intragenic DNA methylation modulates alternative splicing by recruiting MeCP2 to promote exon recognition. Cell Res 23:1256–1269CrossRefPubMedPubMedCentralGoogle Scholar
  53. 53.
    Mellen M, Ayata P, Dewell S, Kriaucionis S, Heintz N (2012) MeCP2 binds to 5hmC enriched in the nervous system. Cell 151:1417–1430CrossRefPubMedPubMedCentralGoogle Scholar
  54. 54.
    Mellios N, Feldman DA, Sheridan SD, Ip JPK, Kwok S, Amoah SK et al (2018) MeCP2-regulated miRNAs control early human neurogenesis through differential effects on ERK and AKT signaling. Mol Psychiatry 23:1051-1065CrossRefPubMedPubMedCentralGoogle Scholar
  55. 55.
    Mnatzakanian GN, Lohi H, Munteanu I, Alfred SE, Yamada T, MacLeod PJ et al (2004) A previously unidentified MECP2 open reading frame defines a new protein isoform relevant to Rett syndrome. Nat Genet 36:339–341CrossRefPubMedGoogle Scholar
  56. 56.
    Namihira M, Nakashima K (2013) Mechanisms of astrocytogenesis in the mammalian brain. Curr Opin Neurobiol 23:921–927CrossRefPubMedGoogle Scholar
  57. 57.
    Nan X, Ng HH, Johnson CA, Laherty CD, Turner BM, Eisenman RN (1998) Transcriptional repression by the methyl-CpG-binding protein MeCP2 involves a histone deacetylase complex. Nature 393:386–389CrossRefPubMedGoogle Scholar
  58. 58.
    Neul JL, Fang P, Barrish J, Lane J, Caeg EB, Smith EO et al (2008) Specific mutations in methyl-CpG-binding protein 2 confer different severity in Rett syndrome. Neurology 70:1313–1321CrossRefPubMedPubMedCentralGoogle Scholar
  59. 59.
    Okabe Y, Kusaga A, Takahashi T, Mitsumasu C, Murai Y, Tanaka E et al (2010) Neural development of methyl-CpG-binding protein 2 null embryonic stem cells: a system for studying Rett syndrome. Brain Res 1360:17–27CrossRefPubMedGoogle Scholar
  60. 60.
    Okabe Y, Takahashi T, Mitsumasu C, Kosai K, Tanaka E, Matsuishi T (2012) Alterations of gene expression and glutamate clearance in astrocytes derived from an MeCP2-null mouse model of Rett syndrome. PLoS One 7:e35354CrossRefPubMedPubMedCentralGoogle Scholar
  61. 61.
    Pan H, Li MR, Nelson P, Bao XH, Wu XR, Yu S (2006) Large deletions of the MECP2 gene in Chinese patients with classical Rett syndrome. Clin Genet 70:418–419CrossRefPubMedGoogle Scholar
  62. 62.
    Perez-Pinera P, Kocak DD, Vockley CM, Adler AF, Kabadi AM, Polstein LR et al (2013) RNA-guided gene activation by CRISPR-Cas9-based transcription factors. Nat Methods 10:973–976CrossRefPubMedPubMedCentralGoogle Scholar
  63. 63.
    Ravn K, Nielsen JB, Skjeldal OH, Kerr A, Hulten M, Schwartz M (2005) Large genomic rearrangements in MECP2. Hum Mutat 25:324CrossRefPubMedGoogle Scholar
  64. 64.
    Reiss AL, Faruque F, Naidu S, Abrams M, Beaty T, Bryan RN et al (1993) Neuroanatomy of Rett syndrome: a volumetric imaging study. Ann Neurol 34:227–234CrossRefPubMedGoogle Scholar
  65. 65.
    Rett A (1966) On a unusual brain atrophy syndrome in hyperammonemia in childhood. Wien Med Wochenschr 116:723–726PubMedGoogle Scholar
  66. 66.
    Ricciardi S, Boggio EM, Grosso S, Lonetti G, Forlani G, Stefanelli G et al (2011) Reduced AKT/mTOR signaling and protein synthesis dysregulation in a Rett syndrome animal model. Hum Mol Genet 20:1182–1196CrossRefPubMedGoogle Scholar
  67. 67.
    Sanjana NE, Cong L, Zhou Y, Cunniff MM, Feng G, Zhang F (2012) A transcription activator-like effector toolbox for genome engineering. Nat Protoc 7:171–192CrossRefPubMedPubMedCentralGoogle Scholar
  68. 68.
    Setoguchi H, Namihira M, Kohyama J, Asano H, Sanosaka T, Nakashima K (2006) Methyl-CpG binding proteins are involved in restricting differentiation plasticity in neurons. J Neurosci Res 84:969–979CrossRefPubMedGoogle Scholar
  69. 69.
    Shahbazian MD, Antalffy B, Armstrong DL, Zoghbi HY (2002) Insight into Rett syndrome: MeCP2 levels display tissue- and cell-specific differences and correlate with neuronal maturation. Hum Mol Genet 11:115–124CrossRefPubMedGoogle Scholar
  70. 70.
    Singh J, Saxena A, Christodoulou J, Ravine D (2008) MECP2 genomic structure and function: insight from ENCODE. Nucleic Acids Res 36:6035–6047CrossRefPubMedPubMedCentralGoogle Scholar
  71. 71.
    Skene PJ, Illingworth RS, Webb S, Kerr AR, James KD, Turner DJ et al (2010) Neuronal MeCP2 is expressed at near histone-octamer levels and globally alters the chromatin state. Mol Cell 37:457–468CrossRefPubMedPubMedCentralGoogle Scholar
  72. 72.
    Svendsen CN, ter Borg MG, Armstrong RJ, Rosser AE, Chandran S, Ostenfeld T et al (1998) A new method for the rapid and long term growth of human neural precursor cells. J Neurosci Methods 85:141–152CrossRefPubMedGoogle Scholar
  73. 73.
    Takahashi K, Tanabe K, Ohnuki M, Narita M, Ichisaka T, Tomoda K et al (2007) Induction of pluripotent stem cells from adult human fibroblasts by defined factors. Cell 131:861–872CrossRefGoogle Scholar
  74. 74.
    Takahashi K, Yamanaka S (2006) Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors. Cell 126:663–676CrossRefGoogle Scholar
  75. 75.
    Tillotson R, Selfridge J, Koerner MV, Gadalla KKE, Guy J, De Sousa D et al (2017) Radically truncated MeCP2 rescues Rett syndrome-like neurological defects. Nature 550:398–401CrossRefPubMedPubMedCentralGoogle Scholar
  76. 76.
    Trappe R, Laccone F, Cobilanschi J, Meins M, Huppke P, Hanefeld F et al (2001) MECP2 mutations in sporadic cases of Rett syndrome are almost exclusively of paternal origin. Am J Hum Genet 68:1093–1101CrossRefPubMedPubMedCentralGoogle Scholar
  77. 77.
    Tsujimura K, Abematsu M, Kohyama J, Namihira M, Nakashima K (2009) Neuronal differentiation of neural precursor cells is promoted by the methyl-CpG-binding protein MeCP2. Exp Neurol 219:104–111CrossRefPubMedGoogle Scholar
  78. 78.
    Tsujimura K, Irie K, Nakashima H, Egashira Y, Fukao Y, Fujiwara M et al (2015) miR-199a links MeCP2 with mTOR signaling and its dysregulation leads to Rett syndrome phenotypes. Cell Rep 12:1887–1901CrossRefGoogle Scholar
  79. 79.
    Veeraragavan S, Wan YW, Connolly DR, Hamilton SM, Ward CS, Soriano S et al (2016) Loss of MeCP2 in the rat models regression, impaired sociability and transcriptional deficits of Rett syndrome. Hum Mol Genet 25:3284–3302CrossRefPubMedPubMedCentralGoogle Scholar
  80. 80.
    Wan M, Lee SS, Zhang X, Houwink-Manville I, Song HR, Amir RE et al (1999) Rett syndrome and beyond: recurrent spontaneous and familial MECP2 mutations at CpG hotspots. Am J Hum Genet 65:1520–1529CrossRefPubMedPubMedCentralGoogle Scholar
  81. 81.
    Young JI, Hong EP, Castle JC, Crespo-Barreto J, Bowman AB, Rose MF et al (2005) Regulation of RNA splicing by the methylation-dependent transcriptional repressor methyl-CpG binding protein 2. Proc Natl Acad Sci U S A 102:17551–17558CrossRefPubMedPubMedCentralGoogle Scholar
  82. 82.
    Yu J, Vodyanik MA, Smuga-Otto K, Antosiewicz-Bourget J, Frane JL, Tian S et al (2007) Induced pluripotent stem cell lines derived from human somatic cells. Science 318:1917–1920CrossRefGoogle Scholar
  83. 83.
    Zhang W, Peterson M, Beyer B, Frankel WN, Zhang ZW (2014) Loss of MeCP2 from forebrain excitatory neurons leads to cortical hyperexcitation and seizures. J Neurosci 34:2754–2763CrossRefPubMedPubMedCentralGoogle Scholar
  84. 84.
    Zou J, Maeder ML, Mali P, Pruett-Miller SM, Thibodeau-Beganny S, Chou BK et al (2009) Gene targeting of a disease-related gene in human induced pluripotent stem and embryonic stem cells. Cell Stem Cell 5:97–110CrossRefPubMedPubMedCentralGoogle Scholar

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Authors and Affiliations

  1. 1.Department of PsychiatryNagoya University Graduate School of MedicineShowa, NagoyaJapan
  2. 2.Institute for Advanced Research, Nagoya UniversityChikusa, NagoyaJapan
  3. 3.Department of Stem Cell Biology and MedicineGraduate School of Medical Sciences, Kyushu UniversityHigashi-ku, FukuokaJapan

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