Modeling Neurodevelopmental Disorders Using Human Pluripotent Stem Cells

Stem Cell Reviews and Reports

Volumn 10, Issue 4, 2014, Pages 494-511

  Telias, Michael ^a   Ben Yosef, Dalit ^a  

^a TEL AVIV UNIVERSITY   (Israel)

Author keywords

Disease models; Electrophysiology; Human pluripotent stem cells; Neural differentiation; Neurodevelopmental disorders

Indexed keywords

ACTION POTENTIAL; ANIMAL; BIOLOGICAL MODEL; CELL DIFFERENTIATION; CYTOLOGY; DEGENERATIVE DISEASE; DEVELOPMENTAL DISORDER; EMBRYONIC STEM CELL; HUMAN; NERVOUS SYSTEM DEVELOPMENT; NEURAL STEM CELL; PATHOLOGY; PHYSIOLOGY; PLURIPOTENT STEM CELL;

ACTION POTENTIALS; ANIMALS; CELL DIFFERENTIATION; DEVELOPMENTAL DISABILITIES; EMBRYONIC STEM CELLS; HUMANS; MODELS, NEUROLOGICAL; NEURAL STEM CELLS; NEURODEGENERATIVE DISEASES; NEUROGENESIS; PLURIPOTENT STEM CELLS;

EID: 84915813061     PISSN: 15508943     EISSN: 15586804     Source Type: Journal    
DOI: 10.1007/s12015-014-9507-2     Document Type: Article

References (217)

1. Goldstein, S., & Reynolds, C. R. (1999). Handbook of neurodevelopmental and genetic disorders in children (p. 602). New York: Guilford Press. xvi.
2. Clegg, J., Gillott, A., & Jones, J. (2013). Conceptual issues in neurodevelopmental disorders: lives out of synch. Curr Opin Psychiatry, 26(3), 289–94.
3. Shinoda, Y., Sadakata, T., & Furuichi, T. (2013). Animal models of autism spectrum disorder (ASD): a synaptic-level approach to autistic-like behavior in mice. Exp Anim, 62(2), 71–8.
4. Gadad, B. S., Hewitson, L., Young, K. A., & German, D. C. (2013). Neuropathology and Animal Models of Autism: Genetic and Environmental Factors. Autism Res Treat, 2013, 731935.
5. Lu, J., Delli-Bovi, L.C., Hecht, J., Folkerth, R., and Sheen, V.L. (2011). Generation of neural stem cells from discarded human fetal cortical tissue. J Vis Exp, (51).
6. Verwer, R. W., Hermens, W. T., Dijkhuizen, P., ter Brake, O., Baker, R. E., Salehi, A., et al. (2002). Cells in human postmortem brain tissue slices remain alive for several weeks in culture. FASEB J, 16(1), 54–60.
7. Mayer, E. J., Carter, D. A., Ren, Y., Hughes, E. H., Rice, C. M., Halfpenny, C. A., et al. (2005). Neural progenitor cells from postmortem adult human retina. Br J Ophthalmol, 89(1), 102–6.
8. Thomson, J. A., Itskovitz-Eldor, J., Shapiro, S. S., Waknitz, M. A., Swiergiel, J. J., Marshall, V. S., et al. (1998). Embryonic stem cell lines derived from human blastocysts. Science, 282(5391), 1145–7.
9. 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(5), 861–72.
10. Peitz, M., Jungverdorben, J., & Brustle, O. (2013). Disease-specific iPS cell models in neuroscience. Curr Mol Med, 13(5), 832–41.
11. Nakano, T., Ando, S., Takata, N., Kawada, M., Muguruma, K., Sekiguchi, K., et al. (2012). Self-formation of optic cups and storable stratified neural retina from human ESCs. Cell Stem Cell, 10(6), 771–85.
12. Lancaster, M. A., Renner, M., Martin, C. A., Wenzel, D., Bicknell, L. S., Hurles, M. E., et al. (2013). Cerebral organoids model human brain development and microcephaly. Nature, 501(7467), 373–9.
13. Little, J. (2000). Epidemiology of neurodevelopmental disorders in children. Prostaglandins Leukot Essent Fatty Acids, 63(1–2), 11–20.
14. Petersen, M. C., Kube, D. A., & Palmer, F. B. (1998). Classification of developmental delays. Semin Pediatr Neurol, 5(1), 2–14.
15. Korkmaz, B. (2011). Theory of mind and neurodevelopmental disorders of childhood. Pediatr Res, 69(5 Pt 2), 101R–8R.
16. Barkovich, A. J., Guerrini, R., Kuzniecky, R. I., Jackson, G. D., & Dobyns, W. B. (2012). A developmental and genetic classification for malformations of cortical development: update 2012. Brain, 135(Pt 5), 1348–69.
17. Nowakowski, R. S., & Hayes, N. L. (1999). CNS development: an overview. Dev Psychopathol, 11(3), 395–417.
18. Stiles, J., & Jernigan, T. L. (2010). The basics of brain development. Neuropsychol Rev, 20(4), 327–48.
19. Hrvoj-Mihic, B., Bienvenu, T., Stefanacci, L., Muotri, A. R., & Semendeferi, K. (2013). Evolution, development, and plasticity of the human brain: from molecules to bones. Front Hum Neurosci, 7, 707.
20. Chaboub, L. S., & Deneen, B. (2012). Developmental origins of astrocyte heterogeneity: the final frontier of CNS development. Dev Neurosci, 34(5), 379–88.
21. Webster, H., & Astrom, K. E. (2009). Gliogenesis: historical perspectives, 1839–1985. Adv Anat Embryol Cell Biol, 202, 1–109.
22. Sequerra, E. B., Costa, M. R., Menezes, J. R., & Hedin-Pereira, C. (2013). Adult neural stem cells: plastic or restricted neuronal fates? Development, 140(16), 3303–9.
23. Bellenchi, G. C., Volpicelli, F., Piscopo, V., Perrone-Capano, C., & di Porzio, U. (2013). Adult neural stem cells: an endogenous tool to repair brain injury? J Neurochem, 124(2), 159–67.
24. Bourgeois, J. P. (1997). Synaptogenesis, heterochrony and epigenesis in the mammalian neocortex. Acta Paediatr Suppl, 422, 27–33.
25. Berlucchi, G., & Buchtel, H. A. (2009). Neuronal plasticity: historical roots and evolution of meaning. Exp Brain Res, 192(3), 307–19.
26. van Loo, K. M., & Martens, G. J. (2007). Genetic and environmental factors in complex neurodevelopmental disorders. Curr Genomics, 8(7), 429–44.
27. Pichichero, M. E. (2009). The PANDAS syndrome. Adv Exp Med Biol, 634, 205–16.
28. Schendel, D. E. (2001). Infection in pregnancy and cerebral palsy. J Am Med Womens Assoc, 56(3), 105–8.
29. Osterhues, A., Ali, N. S., & Michels, K. B. (2013). The role of folic acid fortification in neural tube defects: a review. Crit Rev Food Sci Nutr, 53(11), 1180–90.
30. Volpe, P., Campobasso, G., De Robertis, V., & Rembouskos, G. (2009). Disorders of prosencephalic development. Prenat Diagn, 29(4), 340–54.
31. Schuurmans, C., & Kurrasch, D. M. (2013). Neurodevelopmental consequences of maternal distress: what do we really know? Clin Genet, 83(2), 108–17.
32. Manning, M. A., & Eugene Hoyme, H. (2007). Fetal alcohol spectrum disorders: a practical clinical approach to diagnosis. Neurosci Biobehav Rev, 31(2), 230–8.
33. Sankar, C., & Mundkur, N. (2005). Cerebral palsy-definition, classification, etiology and early diagnosis. Indian J Pediatr, 72(10), 865–8.
34. Ryan, S. G. (1999). Genetic susceptibility to neurodevelopmental disorders. J Child Neurol, 14(3), 187–95.
35. Skuse, D. H. (1997). Genetic factors in the etiology of child psychiatric disorders. Curr Opin Pediatr, 9(4), 354–60.
36. Schendel, D., Rice, C., & Cunniff, C. (2010). The contribution of rare diseases to understanding the epidemiology of neurodevelopmental disabilities. Adv Exp Med Biol, 686, 433–53.
37. Coe, B. P., Girirajan, S., & Eichler, E. E. (2012). A genetic model for neurodevelopmental disease. Curr Opin Neurobiol, 22(5), 829–36.
38. Poduri, A., Evrony, G. D., Cai, X., & Walsh, C. A. (2013). Somatic mutation, genomic variation, and neurological disease. Science, 341(6141), 1237758.
39. Fernandes, A. M., Meletti, T., Guimaraes, R., Stelling, M. P., Marinho, P. A., Valladao, A. S., et al. (2010). Worldwide survey of published procedures to culture human embryonic stem cells. Cell Transplant, 19(5), 509–23.
40. Frumkin, T., Malcov, M., Telias, M., Gold, V., Schwartz, T., Azem, F., et al. (2010). Human embryonic stem cells carrying mutations for severe genetic disorders. Vitro Cell Dev Biol Anim, 46(3–4), 327–36.
41. Vazin, T., & Freed, W. J. (2010). Human embryonic stem cells: derivation, culture, and differentiation: a review. Restor Neurol Neurosci, 28(4), 589–603.
42. Crocco, M. C., Fratnz, N., & Bos-Mikich, A. (2013). Substrates and supplements for hESCs: a critical review. J Assist Reprod Genet, 30(3), 315–23.
43. Nichols, J., & Smith, A. (2012). Pluripotency in the embryo and in culture. Cold Spring Harb Perspect Biol, 4(8), a008128.
44. Deb, K. D., Jayaprakash, A. D., Sharma, V., & Totey, S. (2008). Embryonic stem cells: from markers to market. Rejuvenation Res, 11(1), 19–37.
45. Ameen, C., Strehl, R., Bjorquist, P., Lindahl, A., Hyllner, J., & Sartipy, P. (2008). Human embryonic stem cells: current technologies and emerging industrial applications. Crit Rev Oncol Hematol, 65(1), 54–80.
46. Unger, C., Skottman, H., Blomberg, P., Dilber, M. S., & Hovatta, O. (2008). Good manufacturing practice and clinical-grade human embryonic stem cell lines. Hum Mol Genet, 17(R1), R48–53.
47. Strelchenko, N., & Verlinsky, Y. (2006). Embryonic stem cells from morula. Methods Enzymol, 418, 93–108.
48. Ben-Yosef, D., Amit, A., Malcov, M., Frumkin, T., Ben-Yehudah, A., Eldar, I., et al. (2012). Female sex bias in human embryonic stem cell lines. Stem Cells Dev, 21(3), 363–72.
49. Biancotti, J. C., & Lavon, N. (2012). Derivation, expansion, and characterization of human embryonic stem cell lines from aneuploid embryos. Methods Mol Biol, 873, 163–78.
50. Ben-Yehudah, A., Malcov, M., Frumkin, T., & Ben-Yosef, D. (2012). Mutated human embryonic stem cells for the study of human genetic disorders. Methods Mol Biol, 873, 179–207.
51. Dvash, T., Ben-Yosef, D., & Eiges, R. (2006). Human embryonic stem cells as a powerful tool for studying human embryogenesis. Pediatr Res, 60(2), 111–7.
52. Dvash, T., & Benvenisty, N. (2004). Human embryonic stem cells as a model for early human development. Best Pract Res Clin Obstet Gynaecol, 18(6), 929–40.
53. Gepstein, L. (2002). Derivation and potential applications of human embryonic stem cells. Circ Res, 91(10), 866–76.
54. Darr, H., & Benvenisty, N. (2006). Human embryonic stem cells: the battle between self-renewal and differentiation. Regen Med, 1(3), 317–25.
55. Friedrich Ben-Nun, I., & Benvenisty, N. (2006). Human embryonic stem cells as a cellular model for human disorders. Mol Cell Endocrinol, 252(1–2), 154–9.
56. Ben-Yosef, D., Malcov, M., & Eiges, R. (2008). PGD-derived human embryonic stem cell lines as a powerful tool for the study of human genetic disorders. Mol Cell Endocrinol, 282(1–2), 153–8.
57. Edwards, R. G. (2005). Ethics and moral philosophy in the initiation of IVF, preimplantation diagnosis and stem cells. Reprod Biomed Online, 10(Suppl 1), 1–8.
58. Edwards, R. G. (2002). Personal pathways to embryonic stem cells. Reprod Biomed Online, 4(3), 263–78.
59. Verlinsky, Y., Strelchenko, N., Kukharenko, V., Rechitsky, S., Verlinsky, O., Galat, V., et al. (2005). Human embryonic stem cell lines with genetic disorders. Reprod Biomed Online, 10(1), 105–10.
60. Taei, A., Gourabi, H., Seifinejad, A., Totonchi, M., Shahbazi, E., Valojerdi, M. R., et al. (2010). Derivation of new human embryonic stem cell lines from preimplantation genetic screening and diagnosis-analyzed embryos. Vitro Cell Dev Biol Anim, 46(3–4), 395–402.
61. Jaroudi, S., & Wells, D. (2013). Microarray-CGH for the assessment of aneuploidy in human polar bodies and oocytes. Methods Mol Biol, 957, 267–83.
62. Aran, B., Sole, M., Rodriguez-Piza, I., Parriego, M., Munoz, Y., Boada, M., et al. (2012). Vitrified blastocysts from Preimplantation Genetic Diagnosis (PGD) as a source for human Embryonic Stem Cell (hESC) derivation. J Assist Reprod Genet, 29(10), 1013–20.
63. Liu, Y., Li, Y., Hwang, A., Wang, S. Y., Jia, C. W., Yu, L., et al. (2011). Comparison of three embryo culture methods for derivation of human embryonic stem cells from discarded embryos. Cell Reprogram, 13(3), 233–9.
64. Fan, Y., Luo, Y., Chen, X., & Sun, X. (2010). A modified culture medium increases blastocyst formation and the efficiency of human embryonic stem cell derivation from poor-quality embryos. J Reprod Dev, 56(5), 533–9.
65. Meng, G., Liu, S., Li, X., Krawetz, R., & Rancourt, D. E. (2010). Derivation of human embryonic stem cell lines after blastocyst microsurgery. Biochem Cell Biol, 88(3), 479–90.
66. Tropel, P., Tournois, J., Come, J., Varela, C., Moutou, C., Fragner, P., et al. (2010). High-efficiency derivation of human embryonic stem cell lines following pre-implantation genetic diagnosis. Vitro Cell Dev Biol Anim, 46(3–4), 376–85.
67. Ilic, D., Caceres, E., Lu, S., Julian, P., Foulk, R., & Krtolica, A. (2010). Effect of karyotype on successful human embryonic stem cell derivation. Stem Cells Dev, 19(1), 39–46.
68. Menendez, P., Wang, L., & Bhatia, M. (2005). Genetic manipulation of human embryonic stem cells: a system to study early human development and potential therapeutic applications. Curr Gene Ther, 5(4), 375–85.
69. Epsztejn-Litman, S., & Eiges, R. (2010). Genetic manipulation of human embryonic stem cells. Methods Mol Biol, 584, 387–411.
70. Braam, S. R., Denning, C., & Mummery, C. L. (2010). Genetic manipulation of human embryonic stem cells in serum and feeder-free media. Methods Mol Biol, 584, 413–23.
71. Li, M., Suzuki, K., Kim, N.Y., Liu, G.H., and Izpisua Belmonte, J.C. (2013). A cut above the rest: targeted genome editing technologies in human pluripotent stem cells. J Biol Chem.
72. Takahashi, K., & Yamanaka, S. (2006). Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors. Cell, 126(4), 663–76.
73. Kallur, T., Darsalia, V., Lindvall, O., & Kokaia, Z. (2006). Human fetal cortical and striatal neural stem cells generate region-specific neurons in vitro and differentiate extensively to neurons after intrastriatal transplantation in neonatal rats. J Neurosci Res, 84(8), 1630–44.
74. Kallur, T., Gisler, R., Lindvall, O., & Kokaia, Z. (2008). Pax6 promotes neurogenesis in human neural stem cells. Mol Cell Neurosci, 38(4), 616–28.
75. Darbinyan, A., Kaminski, R., White, M. K., Darbinian, N., & Khalili, K. (2013). Isolation and propagation of primary human and rodent embryonic neural progenitor cells and cortical neurons. Methods Mol Biol, 1078, 45–54.
76. Chailangkarn, T., Acab, A., & Muotri, A. R. (2012). Modeling neurodevelopmental disorders using human neurons. Curr Opin Neurobiol, 22(5), 785–90.
77. Cundiff, P. E., & Anderson, S. A. (2011). Impact of induced pluripotent stem cells on the study of central nervous system disease. Curr Opin Genet Dev, 21(3), 354–61.
78. Wang, H., & Doering, L. C. (2012). Induced pluripotent stem cells to model and treat neurogenetic disorders. Neural Plast, 2012, 346053.
79. Elkabetz, Y., & Studer, L. (2008). Human ESC-derived neural rosettes and neural stem cell progression. Cold Spring Harb Symp Quant Biol, 73, 377–87.
80. Telias, M., Segal, M., & Ben-Yosef, D. (2013). Neural differentiation of Fragile X human Embryonic Stem Cells reveals abnormal patterns of development despite successful neurogenesis. Dev Biol, 374(1), 32–45.
81. Muguruma, K., & Sasai, Y. (2012). In vitro recapitulation of neural development using embryonic stem cells: from neurogenesis to histogenesis. Dev Growth Differ, 54(3), 349–57.
82. Tornero, D., Wattananit, S., Gronning Madsen, M., Koch, P., Wood, J., Tatarishvili, J., et al. (2013). Human induced pluripotent stem cell-derived cortical neurons integrate in stroke-injured cortex and improve functional recovery. Brain.
83. Tonnesen, J., Parish, C. L., Sorensen, A. T., Andersson, A., Lundberg, C., Deisseroth, K., et al. (2011). Functional integration of grafted neural stem cell-derived dopaminergic neurons monitored by optogenetics in an in vitro Parkinson model. PLoS One, 6(3), e17560.
84. Badger, J.L., Cordero-Llana, O., Hartfield, E.M., and Wade-Martins, R. (2014). Parkinson’s disease in a dish - Using stem cells as a molecular tool. Neuropharmacology, 76 Pt A: p. 88–96.
85. Deleidi, M., Cooper, O., Hargus, G., Levy, A., & Isacson, O. (2011). Oct4-induced reprogramming is required for adult brain neural stem cell differentiation into midbrain dopaminergic neurons. PLoS One, 6(5), e19926.
86. Daadi, M. M. (2008). In vitro assays for neural stem cell differentiation: induction of dopaminergic phenotype. Methods Mol Biol, 438, 205–12.
87. Mackay-Sim, A. (2013). Patient-derived stem cells: pathways to drug discovery for brain diseases. Front Cell Neurosci, 7, 29.
88. Boissart, C., Poulet, A., Georges, P., Darville, H., Julita, E., Delorme, R., et al. (2013). Differentiation from human pluripotent stem cells of cortical neurons of the superficial layers amenable to psychiatric disease modeling and high-throughput drug screening. Transl Psychiatry, 3, e294.
89. Di Giorgio, F. P., Carrasco, M. A., Siao, M. C., Maniatis, T., & Eggan, K. (2007). Non-cell autonomous effect of glia on motor neurons in an embryonic stem cell-based ALS model. Nat Neurosci, 10(5), 608–14.
90. Grade, S., Bernardino, L., and Malva, J.O. (2013). Oligodendrogenesis from neural stem cells: Perspectives for remyelinating strategies. Int J Dev Neurosci.
91. Izrael, M., Zhang, P., Kaufman, R., Shinder, V., Ella, R., Amit, M., et al. (2007). Human oligodendrocytes derived from embryonic stem cells: Effect of noggin on phenotypic differentiation in vitro and on myelination in vivo. Mol Cell Neurosci, 34(3), 310–23.
92. Geschwind, D. H., & Levitt, P. (2007). Autism spectrum disorders: developmental disconnection syndromes. Curr Opin Neurobiol, 17(1), 103–11.
93. Zwaigenbaum, L., Bryson, S., & Garon, N. (2013). Early identification of autism spectrum disorders. Behav Brain Res, 251, 133–46.
94. Association, A.P., (2013). Diagnostic and Statistical Manual of Mental Disorders, 5th Edition (DSM-5). American Psychiatric Association
95. Huerta, M., Bishop, S. L., Duncan, A., Hus, V., & Lord, C. (2012). Application of DSM-5 criteria for autism spectrum disorder to three samples of children with DSM-IV diagnoses of pervasive developmental disorders. Am J Psychiatry, 169(10), 1056–64.
96. Rapin, I., & Tuchman, R. F. (2008). What is new in autism? Curr Opin Neurol, 21(2), 143–9.
97. Santangelo, S. L., & Tsatsanis, K. (2005). What is known about autism: genes, brain, and behavior. Am J Pharmacogenomics, 5(2), 71–92.
98. Piggot, J., Shirinyan, D., Shemmassian, S., Vazirian, S., & Alarcon, M. (2009). Neural systems approaches to the neurogenetics of autism spectrum disorders. Neuroscience, 164(1), 247–56.
99. Jeste, S.S. and Geschwind, D.H. (2014). Disentangling the heterogeneity of autism spectrum disorder through genetic findings. Nat Rev Neurol.
100. Autism, Developmental Disabilities Monitoring Network Surveillance Year Principal, I., Centers for Disease, C., and Prevention. (2009). Prevalence of autism spectrum disorders - Autism and Developmental Disabilities Monitoring Network, United States, 2006. MMWR Surveill Summ, 58(10), 1–20.
101. Van Wijngaarden-Cremers, P.J., van Eeten, E., Groen, W.B., Van Deurzen, P.A., Oosterling, I.J., and Van der Gaag, R.J. (2013). Gender and Age Differences in the Core Triad of Impairments in Autism Spectrum Disorders: A Systematic Review and Meta-analysis. J Autism Dev Disord.
102. Lin, M., Pedrosa, E., Shah, A., Hrabovsky, A., Maqbool, S., Zheng, D., et al. (2011). RNA-Seq of human neurons derived from iPS cells reveals candidate long non-coding RNAs involved in neurogenesis and neuropsychiatric disorders. PLoS One, 6(9), e23356.
103. Lin, M., Hrabovsky, A., Pedrosa, E., Wang, T., Zheng, D., & Lachman, H. M. (2012). Allele-biased expression in differentiating human neurons: implications for neuropsychiatric disorders. PLoS One, 7(8), e44017.
104. Stamou, M., Streifel, K. M., Goines, P. E., & Lein, P. J. (2013). Neuronal connectivity as a convergent target of gene x environment interactions that confer risk for Autism Spectrum Disorders. Neurotoxicol Teratol, 36, 3–16.
105. Chanda, S., Marro, S., Wernig, M., & Sudhof, T. C. (2013). Neurons generated by direct conversion of fibroblasts reproduce synaptic phenotype caused by autism-associated neuroligin-3 mutation. Proc Natl Acad Sci U S A, 110(41), 16622–7.
106. DeRosa, B. A., Van Baaren, J. M., Dubey, G. K., Lee, J. M., Cuccaro, M. L., Vance, J. M., et al. (2012). Derivation of autism spectrum disorder-specific induced pluripotent stem cells from peripheral blood mononuclear cells. Neurosci Lett, 516(1), 9–14.
107. Zeng, L., Zhang, P., Shi, L., Yamamoto, V., Lu, W., & Wang, K. (2013). Functional impacts of NRXN1 knockdown on neurodevelopment in stem cell models. PLoS One, 8(3), e59685.
108. Gargus, J. J. (2006). Ion channel functional candidate genes in multigenic neuropsychiatric disease. Biol Psychiatry, 60(2), 177–85.
109. Bader, P. L., Faizi, M., Kim, L. H., Owen, S. F., Tadross, M. R., Alfa, R. W., et al. (2011). Mouse model of Timothy syndrome recapitulates triad of autistic traits. Proc Natl Acad Sci U S A, 108(37), 15432–7.
110. Cohen-Kutner, M., Yahalom, Y., Trus, M., & Atlas, D. (2012). Calcineurin Controls Voltage-Dependent-Inactivation (VDI) of the Normal and Timothy Cardiac Channels. Sci Rep, 2, 366.
111. Pasca, S. P., Portmann, T., Voineagu, I., Yazawa, M., Shcheglovitov, A., Pasca, A. M., et al. (2011). Using iPSC-derived neurons to uncover cellular phenotypes associated with Timothy syndrome. Nat Med, 17(12), 1657–62.
112. Yazawa, M., & Dolmetsch, R. E. (2013). Modeling Timothy syndrome with iPS cells. J Cardiovasc Transl Res, 6(1), 1–9.
113. Krey, J. F., Pasca, S. P., Shcheglovitov, A., Yazawa, M., Schwemberger, R., Rasmusson, R., et al. (2013). Timothy syndrome is associated with activity-dependent dendritic retraction in rodent and human neurons. Nat Neurosci, 16(2), 201–9.
114. Penagarikano, O., Mulle, J. G., & Warren, S. T. (2007). The pathophysiology of fragile x syndrome. Annu Rev Genomics Hum Genet, 8, 109–29.
115. Budimirovic, D. B., & Kaufmann, W. E. (2011). What can we learn about autism from studying fragile X syndrome? Dev Neurosci, 33(5), 379–94.
116. Rinehart, N. J., Cornish, K. M., & Tonge, B. J. (2011). Gender differences in neurodevelopmental disorders: autism and fragile x syndrome. Curr Top Behav Neurosci, 8, 209–29.
117. Hagerman, R. J. (2006). Lessons from fragile X regarding neurobiology, autism, and neurodegeneration. J Dev Behav Pediatr, 27(1), 63–74.
118. Fernandez, E., Rajan, N., & Bagni, C. (2013). The FMRP regulon: from targets to disease convergence. Front Neurosci, 7, 191.
119. Loesch, D., & Hagerman, R. (2012). Unstable mutations in the FMR1 gene and the phenotypes. Adv Exp Med Biol, 769, 78–114.
120. van Eyk, C. L., & Richards, R. I. (2012). Dynamic mutations: where are they now? Adv Exp Med Biol, 769, 55–77.
121. Willemsen, R., Bontekoe, C. J., Severijnen, L. A., & Oostra, B. A. (2002). Timing of the absence of FMR1 expression in full mutation chorionic villi. Hum Genet, 110(6), 601–5.
122. Abitbol, M., Menini, C., Delezoide, A. L., Rhyner, T., Vekemans, M., & Mallet, J. (1993). Nucleus basalis magnocellularis and hippocampus are the major sites of FMR-1 expression in the human fetal brain. Nat Genet, 4(2), 147–53.
123. Hergersberg, M., Matsuo, K., Gassmann, M., Schaffner, W., Luscher, B., Rulicke, T., et al. (1995). Tissue-specific expression of a FMR1/beta-galactosidase fusion gene in transgenic mice. Hum Mol Genet, 4(3), 359–66.
124. Ascano, M., Jr., Mukherjee, N., Bandaru, P., Miller, J. B., Nusbaum, J. D., Corcoran, D. L., et al. (2012). FMRP targets distinct mRNA sequence elements to regulate protein expression. Nature, 492(7429), 382–6.
125. Jayaseelan, S., & Tenenbaum, S. A. (2012). Neurodevelopmental disorders: Signalling pathways of fragile X syndrome. Nature, 492(7429), 359–60.
126. Sidorov, M. S., Auerbach, B. D., & Bear, M. F. (2013). Fragile X mental retardation protein and synaptic plasticity. Mol Brain, 6, 15.
127. Levenga, J., de Vrij, F. M., Buijsen, R. A., Li, T., Nieuwenhuizen, I. M., Pop, A., et al. (2011). Subregion-specific dendritic spine abnormalities in the hippocampus of Fmr1 KO mice. Neurobiol Learn Mem, 95(4), 467–72.
128. Ng, M. C., Yang, Y. L., & Lu, K. T. (2013). Behavioral and synaptic circuit features in a zebrafish model of fragile X syndrome. PLoS One, 8(3), e51456.
129. Friedman, S.H., Dani, N., Rushton, E., and Broadie, K. (2013). Fragile X mental retardation protein regulates trans-synaptic signaling in Drosophila. Dis Model Mech.
130. Eiges, R., Urbach, A., Malcov, M., Frumkin, T., Schwartz, T., Amit, A., et al. (2007). Developmental study of fragile X syndrome using human embryonic stem cells derived from preimplantation genetically diagnosed embryos. Cell Stem Cell, 1(5), 568–77.
131. Urbach, A., Bar-Nur, O., Daley, G. Q., & Benvenisty, N. (2010). Differential modeling of fragile X syndrome by human embryonic stem cells and induced pluripotent stem cells. Cell Stem Cell, 6(5), 407–11.
132. Sheridan, S. D., Theriault, K. M., Reis, S. A., Zhou, F., Madison, J. M., Daheron, L., et al. (2011). Epigenetic characterization of the FMR1 gene and aberrant neurodevelopment in human induced pluripotent stem cell models of fragile X syndrome. PLoS One, 6(10), e26203.
133. Bar-Nur, O., Caspi, I., & Benvenisty, N. (2012). Molecular analysis of FMR1 reactivation in fragile-X induced pluripotent stem cells and their neuronal derivatives. J Mol Cell Biol, 4(3), 180–3.
134. Castren, M., Tervonen, T., Karkkainen, V., Heinonen, S., Castren, E., Larsson, K., et al. (2005). Altered differentiation of neural stem cells in fragile X syndrome. Proc Natl Acad Sci U S A, 102(49), 17834–9.
135. Alisch, R. S., Wang, T., Chopra, P., Visootsak, J., Conneely, K. N., & Warren, S. T. (2013). Genome-wide analysis validates aberrant methylation in fragile X syndrome is specific to the FMR1 locus. BMC Med Genet, 14, 18.
136. Hagerman, P. (2013). Fragile X-associated tremor/ataxia syndrome (FXTAS): pathology and mechanisms. Acta Neuropathol, 126(1), 1–19.
137. Hagerman, R., & Hagerman, P. (2013). Advances in clinical and molecular understanding of the FMR1 premutation and fragile X-associated tremor/ataxia syndrome. Lancet Neurol, 12(8), 786–98.
138. Liu, J., Koscielska, K. A., Cao, Z., Hulsizer, S., Grace, N., Mitchell, G., et al. (2012). Signaling defects in iPSC-derived fragile X premutation neurons. Hum Mol Genet, 21(17), 3795–805.
139. Weng, S. M., Bailey, M. E., & Cobb, S. R. (2011). Rett syndrome: from bed to bench. Pediatr Neonatol, 52(6), 309–16.
140. Na, E. S., Nelson, E. D., Kavalali, E. T., & Monteggia, L. M. (2013). The impact of MeCP2 loss- or gain-of-function on synaptic plasticity. Neuropsychopharmacology, 38(1), 212–9.
141. Guerrini, R., & Parrini, E. (2012). Epilepsy in Rett syndrome, and CDKL5- and FOXG1-gene-related encephalopathies. Epilepsia, 53(12), 2067–78.
142. 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(5), 1093–101.
143. Williamson, S. L., & Christodoulou, J. (2006). Rett syndrome: new clinical and molecular insights. Eur J Hum Genet, 14(8), 896–903.
144. Neul, J. L. (2012). The relationship of Rett syndrome and MECP2 disorders to autism. Dialogues Clin Neurosci, 14(3), 253–62.
145. Percy, A. K. (2011). Rett syndrome: exploring the autism link. Arch Neurol, 68(8), 985–9.
146. Hotta, A., Cheung, A. Y., Farra, N., Vijayaragavan, K., Seguin, C. A., Draper, J. S., et al. (2009). Isolation of human iPS cells using EOS lentiviral vectors to select for pluripotency. Nat Methods, 6(5), 370–6.
147. Muotri, A. R., Marchetto, M. C., Coufal, N. G., Oefner, R., Yeo, G., Nakashima, K., et al. (2010). L1 retrotransposition in neurons is modulated by MeCP2. Nature, 468(7322), 443–6.
148. Marchetto, M. C., Carromeu, C., Acab, A., Yu, D., Yeo, G. W., Mu, Y., et al. (2010). A model for neural development and treatment of Rett syndrome using human induced pluripotent stem cells. Cell, 143(4), 527–39.
149. Studer, L. (2010). Neuroscience: Excessive mobility interrupted. Nature, 468(7322), 383–4.
150. Walsh, R. M., & Hochedlinger, K. (2010). Modeling Rett syndrome with stem cells. Cell, 143(4), 499–500.
151. Di Stefano, B., Maffioletti, S. M., Gentner, B., Ungaro, F., Schira, G., Naldini, L., et al. (2011). A microRNA-based system for selecting and maintaining the pluripotent state in human induced pluripotent stem cells. Stem Cells, 29(11), 1684–95.
152. Pomp, O., Dreesen, O., Leong, D. F., Meller-Pomp, O., Tan, T. T., Zhou, F., et al. (2011). Unexpected X chromosome skewing during culture and reprogramming of human somatic cells can be alleviated by exogenous telomerase. Cell Stem Cell, 9(2), 156–65.
153. Cheung, A. Y., Horvath, L. M., 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(11), 2103–15.
154. Ananiev, G., Williams, E. C., 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(9), e25255.
155. Kim, K. Y., Hysolli, E., & Park, I. H. (2011). Neuronal maturation defect in induced pluripotent stem cells from patients with Rett syndrome. Proc Natl Acad Sci U S A, 108(34), 14169–74.
156. Farra, N., Zhang, W. B., Pasceri, P., Eubanks, J. H., Salter, M. W., & Ellis, J. (2012). Rett syndrome induced pluripotent stem cell-derived neurons reveal novel neurophysiological alterations. Mol Psychiatry, 17(12), 1261–71.
157. Larimore, J., Ryder, P. V., Kim, K. Y., Ambrose, L. A., Chapleau, C., Calfa, G., et al. (2013). MeCP2 regulates the synaptic expression of a Dysbindin-BLOC-1 network component in mouse brain and human induced pluripotent stem cell-derived neurons. PLoS One, 8(6), e65069.
158. Amenduni, M., De Filippis, R., Cheung, A. Y., Disciglio, V., Epistolato, M. C., Ariani, F., et al. (2011). iPS cells to model CDKL5-related disorders. Eur J Hum Genet, 19(12), 1246–55.
159. Ricciardi, S., Ungaro, F., Hambrock, M., Rademacher, N., Stefanelli, G., Brambilla, D., et al. (2012). CDKL5 ensures excitatory synapse stability by reinforcing NGL-1-PSD95 interaction in the postsynaptic compartment and is impaired in patient iPSC-derived neurons. Nat Cell Biol, 14(9), 911–23.
160. Opitz, J. M., & Gilbert-Barness, E. F. (1990). Reflections on the pathogenesis of Down syndrome. Am J Med Genet Suppl, 7, 38–51.
161. Sturgeon, X., Le, T., Ahmed, M. M., & Gardiner, K. J. (2012). Pathways to cognitive deficits in Down syndrome. Prog Brain Res, 197, 73–100.
162. Patterson, T., Rapsey, C. M., & Glue, P. (2013). Systematic review of cognitive development across childhood in Down syndrome: implications for treatment interventions. J Intellect Disabil Res, 57(4), 306–18.
163. Lott, I. T. (2012). Neurological phenotypes for Down syndrome across the life span. Prog Brain Res, 197, 101–21.
164. Parker, S. E., Mai, C. T., Canfield, M. A., Rickard, R., Wang, Y., Meyer, R. E., et al. (2010). Updated National Birth Prevalence estimates for selected birth defects in the United States, 2004–2006. Birth Defects Res A Clin Mol Teratol, 88(12), 1008–16.
165. Weijerman, M. E., & de Winter, J. P. (2010). Clinical practice. The care of children with Down syndrome. Eur J Pediatr, 169(12), 1445–52.
166. Weksler, M. E., Szabo, P., Relkin, N. R., Reidenberg, M. M., Weksler, B. B., & Coppus, A. M. (2013). Alzheimer’s disease and Down’s syndrome: treating two paths to dementia. Autoimmun Rev, 12(6), 670–3.
167. Cardenas, A. M., Ardiles, A. O., Barraza, N., Baez-Matus, X., & Caviedes, P. (2012). Role of tau protein in neuronal damage in Alzheimer’s disease and Down syndrome. Arch Med Res, 43(8), 645–54.
168. Creau, N. (2012). Molecular and cellular alterations in Down syndrome: toward the identification of targets for therapeutics. Neural Plast, 2012, 171639.
169. Canzonetta, C., Mulligan, C., Deutsch, S., Ruf, S., O’Doherty, A., Lyle, R., et al. (2008). DYRK1A-dosage imbalance perturbs NRSF/REST levels, deregulating pluripotency and embryonic stem cell fate in Down syndrome. Am J Hum Genet, 83(3), 388–400.
170. Hernandez, D., Mee, P. J., Martin, J. E., Tybulewicz, V. L., & Fisher, E. M. (1999). Transchromosomal mouse embryonic stem cell lines and chimeric mice that contain freely segregating segments of human chromosome 21. Hum Mol Genet, 8(5), 923–33.
171. Doherty, A. M., & Fisher, E. M. (2003). Microcell-mediated chromosome transfer (MMCT): small cells with huge potential. Mamm Genome, 14(9), 583–92.
172. Biancotti, J. C., Narwani, K., Buehler, N., Mandefro, B., Golan-Lev, T., Yanuka, O., et al. (2010). Human embryonic stem cells as models for aneuploid chromosomal syndromes. Stem Cells, 28(9), 1530–40.
173. Mou, X., Wu, Y., Cao, H., Meng, Q., Wang, Q., & Sun, C. (2012). Generation of disease-specific induced pluripotent stem cells from patients with different karyotypes of Down syndrome. Stem Cell Res Ther, 3(2), 14.
174. Chou, S. T., Byrska-Bishop, M., Tober, J. M., Yao, Y., Vandorn, D., Opalinska, J. B., et al. (2012). Trisomy 21-associated defects in human primitive hematopoiesis revealed through induced pluripotent stem cells. Proc Natl Acad Sci U S A, 109(43), 17573–8.
175. Maclean, G. A., Menne, T. F., Guo, G., Sanchez, D. J., Park, I. H., Daley, G. Q., et al. (2012). Altered hematopoiesis in trisomy 21 as revealed through in vitro differentiation of isogenic human pluripotent cells. Proc Natl Acad Sci U S A, 109(43), 17567–72.
176. Li, L. B., Chang, K. H., Wang, P. R., Hirata, R. K., Papayannopoulou, T., & Russell, D. W. (2012). Trisomy correction in Down syndrome induced pluripotent stem cells. Cell Stem Cell, 11(5), 615–9.
177. Lu, H. E., Yang, Y. C., Chen, S. M., Su, H. L., Huang, P. C., Tsai, M. S., et al. (2013). Modeling neurogenesis impairment in Down syndrome with induced pluripotent stem cells from Trisomy 21 amniotic fluid cells. Exp Cell Res, 319(4), 498–505.
178. Briggs, J. A., Sun, J., Shepherd, J., Ovchinnikov, D. A., Chung, T. L., Nayler, S. P., et al. (2013). Integration-free induced pluripotent stem cells model genetic and neural developmental features of down syndrome etiology. Stem Cells, 31(3), 467–78.
179. Weick, J. P., Held, D. L., Bonadurer, G. F., 3rd, Doers, M. E., Liu, Y., Maguire, C., et al. (2013). Deficits in human trisomy 21 iPSCs and neurons. Proc Natl Acad Sci U S A, 110(24), 9962–7.
180. Jiang, J., Jing, Y., Cost, G. J., Chiang, J. C., Kolpa, H. J., Cotton, A. M., et al. (2013). Translating dosage compensation to trisomy 21. Nature, 500(7462), 296–300.
181. Shi, Y., Kirwan, P., Smith, J., MacLean, G., Orkin, S. H., & Livesey, F. J. (2012). A human stem cell model of early Alzheimer’s disease pathology in Down syndrome. Sci Transl Med, 4(124), 124ra29.
182. Cassidy, S. B., Schwartz, S., Miller, J. L., & Driscoll, D. J. (2012). Prader-Willi syndrome. Genet Med, 14(1), 10–26.
183. Kernohan, K. D., & Berube, N. G. (2010). Genetic and epigenetic dysregulation of imprinted genes in the brain. Epigenomics, 2(6), 743–63.
184. Thibert, R. L., Larson, A. M., Hsieh, D. T., Raby, A. R., & Thiele, E. A. (2013). Neurologic manifestations of Angelman syndrome. Pediatr Neurol, 48(4), 271–9.
185. Whittington, J., & Holland, A. (2010). Neurobehavioral phenotype in Prader-Willi syndrome. Am J Med Genet C Semin Med Genet, 154C(4), 438–47.
186. Chamberlain, S. J., & Lalande, M. (2010). Neurodevelopmental disorders involving genomic imprinting at human chromosome 15q11-q13. Neurobiol Dis, 39(1), 13–20.
187. Yang, J., Cai, J., Zhang, Y., Wang, X., Li, W., Xu, J., et al. (2010). Induced pluripotent stem cells can be used to model the genomic imprinting disorder Prader-Willi syndrome. J Biol Chem, 285(51), 40303–11.
188. Chamberlain, S. J., Chen, P. F., Ng, K. Y., Bourgois-Rocha, F., Lemtiri-Chlieh, F., Levine, E. S., et al. (2010). Induced pluripotent stem cell models of the genomic imprinting disorders Angelman and Prader-Willi syndromes. Proc Natl Acad Sci U S A, 107(41), 17668–73.
189. Nyhan, W. L. (1997). The recognition of Lesch-Nyhan syndrome as an inborn error of purine metabolism. J Inherit Metab Dis, 20(2), 171–8.
190. Jinnah, H. A., Visser, J. E., Harris, J. C., Verdu, A., Larovere, L., Ceballos-Picot, I., et al. (2006). Delineation of the motor disorder of Lesch-Nyhan disease. Brain, 129(Pt 5), 1201–17.
191. Nyhan, W.L., O’Neill, J.P., Jinnah, H.A., and Harris, J.C., Lesch-Nyhan Syndrome, in GeneReviews, R.A. Pagon, et al., Editors. 1993: Seattle (WA).
192. Visser, J. E., Bar, P. R., & Jinnah, H. A. (2000). Lesch-Nyhan disease and the basal ganglia. Brain Res Brain Res Rev, 32(2–3), 449–75.
193. Saito, Y., & Takashima, S. (2000). Neurotransmitter changes in the pathophysiology of Lesch-Nyhan syndrome. Brain Dev, 22(Suppl 1), S122–31.
194. Chen, B.C., Balasubramaniam, S., McGown, I.N., O’Neill, J.P., Chng, G.S., Keng, W.T., et al. (2013). Treatment of Lesch-Nyhan disease with S-adenosylmethionine: Experience with five young Malaysians, including a girl. Brain Dev.
195. Kallay, K., Liptai, Z., Benyo, G., Kassa, C., Goda, V., Sinko, J., et al. (2012). Successful unrelated umbilical cord blood transplantation in Lesch-Nyhan syndrome. Metab Brain Dis, 27(2), 193–6.
196. Visser, J. E., Schretlen, D. J., Bloem, B. R., & Jinnah, H. A. (2011). Levodopa is not a useful treatment for Lesch-Nyhan disease. Mov Disord, 26(4), 746–9.
197. Urbach, A., Schuldiner, M., & Benvenisty, N. (2004). Modeling for Lesch-Nyhan disease by gene targeting in human embryonic stem cells. Stem Cells, 22(4), 635–41.
198. Park, I. H., Arora, N., Huo, H., Maherali, N., Ahfeldt, T., Shimamura, A., et al. (2008). Disease-specific induced pluripotent stem cells. Cell, 134(5), 877–86.
199. Khan, I. F., Hirata, R. K., Wang, P. R., Li, Y., Kho, J., Nelson, A., et al. (2010). Engineering of human pluripotent stem cells by AAV-mediated gene targeting. Mol Ther, 18(6), 1192–9.
200. Mastrangelo, L., Kim, J. E., Miyanohara, A., Kang, T. H., & Friedmann, T. (2012). Purinergic signaling in human pluripotent stem cells is regulated by the housekeeping gene encoding hypoxanthine guanine phosphoribosyltransferase. Proc Natl Acad Sci U S A, 109(9), 3377–82.
201. Mekhoubad, S., Bock, C., de Boer, A. S., Kiskinis, E., Meissner, A., & Eggan, K. (2012). Erosion of dosage compensation impacts human iPSC disease modeling. Cell Stem Cell, 10(5), 595–609.
202. Sidransky, E. (2012). Gaucher disease: insights from a rare Mendelian disorder. Discov Med, 14(77), 273–81.
203. Grabowski, G. A. (2012). Gaucher disease and other storage disorders. Hematology Am Soc Hematol Educ Program, 2012, 13–8.
204. Rosenbloom, B. E., & Weinreb, N. J. (2013). Gaucher disease: a comprehensive review. Crit Rev Oncog, 18(3), 163–75.
205. Vitner, E. B., & Futerman, A. H. (2013). Neuronal forms of Gaucher disease. Handb Exp Pharmacol, 216, 405–19.
206. Panicker, L. M., Miller, D., Park, T. S., Patel, B., Azevedo, J. L., Awad, O., et al. (2012). Induced pluripotent stem cell model recapitulates pathologic hallmarks of Gaucher disease. Proc Natl Acad Sci U S A, 109(44), 18054–9.
207. Tiscornia, G., Vivas, E. L., Matalonga, L., Berniakovich, I., Barragan Monasterio, M., Eguizabal, C., et al. (2013). Neuronopathic Gaucher’s disease: induced pluripotent stem cells for disease modelling and testing chaperone activity of small compounds. Hum Mol Genet, 22(4), 633–45.
208. Byrne, J. A. (2008). Generation of isogenic pluripotent stem cells. Hum Mol Genet, 17(R1), 37–41.
209. Soldner, F., Laganiere, J., Cheng, A. W., Hockemeyer, D., Gao, Q., Alagappan, R., et al. (2011). Generation of isogenic pluripotent stem cells differing exclusively at two early onset Parkinson point mutations. Cell, 146(2), 318–31.
210. Conti, L., & Cattaneo, E. (2010). Neural stem cell systems: physiological players or in vitro entities? Nat Rev Neurosci, 11(3), 176–87.
211. Chambers, S. M., Mica, Y., Studer, L., & Tomishima, M. J. (2011). Converting human pluripotent stem cells to neural tissue and neurons to model neurodegeneration. Methods Mol Biol, 793, 87–97.
212. Chambers, S. M., Fasano, C. A., Papapetrou, E. P., Tomishima, M., Sadelain, M., & Studer, L. (2009). Highly efficient neural conversion of human ES and iPS cells by dual inhibition of SMAD signaling. Nat Biotechnol, 27(3), 275–80.
213. LaVaute, T. M., Yoo, Y. D., Pankratz, M. T., Weick, J. P., Gerstner, J. R., & Zhang, S. C. (2009). Regulation of neural specification from human embryonic stem cells by BMP and FGF. Stem Cells, 27(8), 1741–9.
214. Li, X. J., Hu, B. Y., Jones, S. A., Zhang, Y. S., Lavaute, T., Du, Z. W., et al. (2008). Directed differentiation of ventral spinal progenitors and motor neurons from human embryonic stem cells by small molecules. Stem Cells, 26(4), 886–93.
215. Johnson, M. A., Weick, J. P., Pearce, R. A., & Zhang, S. C. (2007). Functional neural development from human embryonic stem cells: accelerated synaptic activity via astrocyte coculture. J Neurosci, 27(12), 3069–77.
216. Zhang, Y., Pak, C., Han, Y., Ahlenius, H., Zhang, Z., Chanda, S., et al. (2013). Rapid single-step induction of functional neurons from human pluripotent stem cells. Neuron, 78(5), 785–98.
217. Kim, J. E., O’Sullivan, M. L., Sanchez, C. A., Hwang, M., Israel, M. A., Brennand, K., et al. (2011). Investigating synapse formation and function using human pluripotent stem cell-derived neurons. Proc Natl Acad Sci U S A, 108(7), 3005–10.