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Reprogramming patient-derived cells to study the epilepsies

Abstract

The epilepsies and related disorders of brain circuitry present significant challenges associated with the use of human cells to study disease mechanisms and develop new therapies. Some of these obstacles are being overcome through the use of induced pluripotent stem cells to obtain patient-derived neural cells for in vitro studies and as a source of cell-based treatments. The field is evolving rapidly with the addition of genome-editing approaches and expanding protocols for generating different neural cell types and three-dimensional tissues, but the application of these techniques to neurological disorders, and particularly to the epilepsies, is in its infancy. We discuss the progress made and the distinct advantages and limitations of using patient-derived cells to study or treat epilepsy, as well as critical future directions for the field.

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Figure 1: iPSC differentiation into neural cell types to study epilepsy.
Figure 2: Epilepsy-patient-derived iPSCs may be differentiated into multiple cell types for studies of the mechanisms involved in sudden unexpected death in epilepsy.

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References

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

    Article  CAS  PubMed  Google Scholar 

  2. Takahashi, K. et al. Induction of pluripotent stem cells from adult human fibroblasts by defined factors. Cell 131, 861–872 (2007).

    Article  CAS  PubMed  Google Scholar 

  3. Thomson, J.A. et al. Embryonic stem cell lines derived from human blastocysts. Science 282, 1145–1147 (1998).

    CAS  PubMed  Google Scholar 

  4. Dimos, J.T. et al. Induced pluripotent stem cells generated from patients with ALS can be differentiated into motor neurons. Science 321, 1218–1221 (2008).

    CAS  PubMed  Google Scholar 

  5. Park, I.H. et al. Disease-specific induced pluripotent stem cells. Cell 134, 877–886 (2008).

    CAS  PubMed  PubMed Central  Google Scholar 

  6. Srikanth, P. & Young-Pearse, T.L. Stem cells on the brain: modeling neurodevelopmental and neurodegenerative diseases using human induced pluripotent stem cells. J. Neurogenet. 28, 5–29 (2014).

    CAS  PubMed  PubMed Central  Google Scholar 

  7. Paşca, S.P., Panagiotakos, G. & Dolmetsch, R.E. Generating human neurons in vitro and using them to understand neuropsychiatric disease. Annu. Rev. Neurosci. 37, 479–501 (2014).

    PubMed  Google Scholar 

  8. Okano, H. & Yamanaka, S. iPS cell technologies: significance and applications to CNS regeneration and disease. Mol. Brain 7, 22 (2014).

    PubMed  PubMed Central  Google Scholar 

  9. Sandoe, J. & Eggan, K. Opportunities and challenges of pluripotent stem cell neurodegenerative disease models. Nat. Neurosci. 16, 780–789 (2013).

    CAS  PubMed  Google Scholar 

  10. Lu, P. et al. Long-distance axonal growth from human induced pluripotent stem cells after spinal cord injury. Neuron 83, 789–796 (2014).

    CAS  PubMed  PubMed Central  Google Scholar 

  11. Hargus, G. et al. Differentiated Parkinson patient-derived induced pluripotent stem cells grow in the adult rodent brain and reduce motor asymmetry in Parkinsonian rats. Proc. Natl. Acad. Sci. USA 107, 15921–15926 (2010).

    CAS  PubMed  PubMed Central  Google Scholar 

  12. Wang, S. et al. Human iPSC-derived oligodendrocyte progenitor cells can myelinate and rescue a mouse model of congenital hypomyelination. Cell Stem Cell 12, 252–264 (2013).

    CAS  PubMed  PubMed Central  Google Scholar 

  13. Oki, K. et al. Human-induced pluripotent stem cells form functional neurons and improve recovery after grafting in stroke-damaged brain. Stem Cells 30, 1120–1133 (2012).

    CAS  PubMed  Google Scholar 

  14. Chin, M.H. et al. Induced pluripotent stem cells and embryonic stem cells are distinguished by gene expression signatures. Cell Stem Cell 5, 111–123 (2009).

    CAS  PubMed  PubMed Central  Google Scholar 

  15. Guenther, M.G. et al. Chromatin structure and gene expression programs of human embryonic and induced pluripotent stem cells. Cell Stem Cell 7, 249–257 (2010).

    CAS  PubMed  PubMed Central  Google Scholar 

  16. Stadtfeld, M. & Hochedlinger, K. Induced pluripotency: history, mechanisms, and applications. Genes Dev. 24, 2239–2263 (2010).

    CAS  PubMed  PubMed Central  Google Scholar 

  17. Hanna, J.H., Saha, K. & Jaenisch, R. Pluripotency and cellular reprogramming: facts, hypotheses, unresolved issues. Cell 143, 508–525 (2010).

    CAS  PubMed  PubMed Central  Google Scholar 

  18. Loh, Y.H. et al. Generation of induced pluripotent stem cells from human blood. Blood 113, 5476–5479 (2009).

    CAS  PubMed  PubMed Central  Google Scholar 

  19. Seki, T. et al. Generation of induced pluripotent stem cells from human terminally differentiated circulating T cells. Cell Stem Cell 7, 11–14 (2010).

    CAS  PubMed  Google Scholar 

  20. Okita, K. et al. 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 (2013).

    CAS  PubMed  Google Scholar 

  21. Fusaki, N., Ban, H., Nishiyama, A., Saeki, K. & Hasegawa, M. 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 (2009).

    CAS  PubMed  PubMed Central  Google Scholar 

  22. Yu, J. et al. Human induced pluripotent stem cells free of vector and transgene sequences. Science 324, 797–801 (2009).

    CAS  PubMed  PubMed Central  Google Scholar 

  23. Müller, F.J. et al. A bioinformatic assay for pluripotency in human cells. Nat. Methods 8, 315–317 (2011).

    PubMed  PubMed Central  Google Scholar 

  24. Bock, C. et al. Reference maps of human ES and iPS cell variation enable high-throughput characterization of pluripotent cell lines. Cell 144, 439–452 (2011).

    CAS  PubMed  PubMed Central  Google Scholar 

  25. Theunissen, T.W. & Jaenisch, R. Molecular control of induced pluripotency. Cell Stem Cell 14, 720–734 (2014).

    CAS  PubMed  PubMed Central  Google Scholar 

  26. Morizane, A. et al. Direct comparison of autologous and allogeneic transplantation of iPSC-derived neural cells in the brain of a nonhuman primate. Stem Cell Reports 1, 283–292 (2013).

    CAS  PubMed  PubMed Central  Google Scholar 

  27. Marchetto, M.C., Brennand, K.J., Boyer, L.F. & Gage, F.H. Induced pluripotent stem cells (iPSCs) and neurological disease modeling: progress and promises. Hum. Mol. Genet. 20, R109–R115 (2011).

    CAS  PubMed  PubMed Central  Google Scholar 

  28. Chailangkarn, T., Acab, A. & Muotri, A.R. Modeling neurodevelopmental disorders using human neurons. Curr. Opin. Neurobiol. 22, 785–790 (2012).

    CAS  PubMed  PubMed Central  Google Scholar 

  29. Jang, J. et al. Induced pluripotent stem cells for modeling of pediatric neurological disorders. Biotechnol. J. 9, 871–881 (2014).

    CAS  PubMed  Google Scholar 

  30. Wainger, B.J. et al. Intrinsic membrane hyperexcitability of amyotrophic lateral sclerosis patient-derived motor neurons. Cell Rep. 7, 1–11 (2014).

    CAS  PubMed  PubMed Central  Google Scholar 

  31. Lancaster, M.A. et al. Cerebral organoids model human brain development and microcephaly. Nature 501, 373–379 (2013).

    CAS  PubMed  Google Scholar 

  32. Brodie, M.J., Barry, S.J., Bamagous, G.A., Norrie, J.D. & Kwan, P. Patterns of treatment response in newly diagnosed epilepsy. Neurology 78, 1548–1554 (2012).

    CAS  PubMed  PubMed Central  Google Scholar 

  33. Miller, J.D. et al. Human iPSC-based modeling of late-onset disease via progerin-induced aging. Cell Stem Cell 13, 691–705 (2013).

    CAS  PubMed  PubMed Central  Google Scholar 

  34. Mekhoubad, S. et al. Erosion of dosage compensation impacts human iPSC disease modeling. Cell Stem Cell 10, 595–609 (2012).

    CAS  PubMed  PubMed Central  Google Scholar 

  35. Tomoda, K. et al. Derivation conditions impact X-inactivation status in female human induced pluripotent stem cells. Cell Stem Cell 11, 91–99 (2012).

    CAS  PubMed  PubMed Central  Google Scholar 

  36. Zeng, H. et al. Large-scale cellular-resolution gene profiling in human neocortex reveals species-specific molecular signatures. Cell 149, 483–496 (2012).

    CAS  PubMed  PubMed Central  Google Scholar 

  37. Wang, X., Tsai, J.W., LaMonica, B. & Kriegstein, A.R. A new subtype of progenitor cell in the mouse embryonic neocortex. Nat. Neurosci. 14, 555–561 (2011).

    CAS  PubMed  PubMed Central  Google Scholar 

  38. LaMonica, B.E., Lui, J.H., Wang, X. & Kriegstein, A.R. OSVZ progenitors in the human cortex: an updated perspective on neurodevelopmental disease. Curr. Opin. Neurobiol. 22, 747–753 (2012).

    CAS  PubMed  PubMed Central  Google Scholar 

  39. Shcheglovitov, A. et al. SHANK3 and IGF1 restore synaptic deficits in neurons from 22q13 deletion syndrome patients. Nature 503, 267–271 (2013).

    CAS  PubMed  PubMed Central  Google Scholar 

  40. Wang, X., Xu, Q., Bey, A.L., Lee, Y. & Jiang, Y.H. Transcriptional and functional complexity of Shank3 provides a molecular framework to understand the phenotypic heterogeneity of SHANK3 causing autism and Shank3 mutant mice. Mol. Autism 5, 30 (2014).

    CAS  PubMed  PubMed Central  Google Scholar 

  41. Yoon, K.J. et al. Modeling a genetic risk for schizophrenia in iPSCs and mice reveals neural stem cell deficits associated with adherens junctions and polarity. Cell Stem Cell 15, 79–91 (2014).

    CAS  PubMed  PubMed Central  Google Scholar 

  42. Dolce, A., Ben-Zeev, B., Naidu, S. & Kossoff, E.H. Rett syndrome and epilepsy: an update for child neurologists. Pediatr. Neurol. 48, 337–345 (2013).

    PubMed  Google Scholar 

  43. Dajani, R., Koo, S.E., Sullivan, G.J. & Park, I.H. Investigation of Rett syndrome using pluripotent stem cells. J. Cell. Biochem. 114, 2446–2453 (2013).

    CAS  PubMed  PubMed Central  Google Scholar 

  44. Marchetto, M.C. et al. A model for neural development and treatment of Rett syndrome using human induced pluripotent stem cells. Cell 143, 527–539 (2010).

    CAS  PubMed  PubMed Central  Google Scholar 

  45. Cheung, A.Y. et al. Isolation of MECP2-null Rett Syndrome patient hiPS cells and isogenic controls through X-chromosome inactivation. Hum. Mol. Genet. 20, 2103–2115 (2011).

    CAS  PubMed  PubMed Central  Google Scholar 

  46. Ananiev, G., Williams, E.C., Li, H. & Chang, Q. 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, e25255 (2011).

    CAS  PubMed  PubMed Central  Google Scholar 

  47. Kim, K.Y., Hysolli, E. & Park, I.H. Neuronal maturation defect in induced pluripotent stem cells from patients with Rett syndrome. Proc. Natl. Acad. Sci. USA 108, 14169–14174 (2011).

    CAS  PubMed  PubMed Central  Google Scholar 

  48. Williams, E.C. et al. Mutant astrocytes differentiated from Rett syndrome patients-specific iPSCs have adverse effects on wild-type neurons. Hum. Mol. Genet. 23, 2968–2980 (2014).

    CAS  PubMed  PubMed Central  Google Scholar 

  49. Berry-Kravis, E. Epilepsy in fragile X syndrome. Dev. Med. Child Neurol. 44, 724–728 (2002).

    PubMed  Google Scholar 

  50. Wang, T., Bray, S.M. & Warren, S.T. New perspectives on the biology of fragile X syndrome. Curr. Opin. Genet. Dev. 22, 256–263 (2012).

    CAS  PubMed  PubMed Central  Google Scholar 

  51. Eiges, R. et al. Establishment of human embryonic stem cell-transfected clones carrying a marker for undifferentiated cells. Curr. Biol. 11, 514–518 (2001).

    CAS  PubMed  Google Scholar 

  52. Urbach, A., Bar-Nur, O., Daley, G.Q. & Benvenisty, N. Differential modeling of fragile X syndrome by human embryonic stem cells and induced pluripotent stem cells. Cell Stem Cell 6, 407–411 (2010).

    CAS  PubMed  PubMed Central  Google Scholar 

  53. Sheridan, S.D. et al. Epigenetic characterization of the FMR1 gene and aberrant neurodevelopment in human induced pluripotent stem cell models of fragile X syndrome. PLoS ONE 6, e26203 (2011).

    CAS  PubMed  PubMed Central  Google Scholar 

  54. Liu, J. et al. Signaling defects in iPSC-derived fragile X premutation neurons. Hum. Mol. Genet. 21, 3795–3805 (2012).

    CAS  PubMed  PubMed Central  Google Scholar 

  55. Telias, M., Segal, M. & Ben-Yosef, D. Neural differentiation of Fragile X human embryonic stem cells reveals abnormal patterns of development despite successful neurogenesis. Dev. Biol. 374, 32–45 (2013).

    CAS  PubMed  Google Scholar 

  56. Splawski, I. et al. Ca(V)1.2 calcium channel dysfunction causes a multisystem disorder including arrhythmia and autism. Cell 119, 19–31 (2004).

    CAS  PubMed  Google Scholar 

  57. Yazawa, M. et al. Using induced pluripotent stem cells to investigate cardiac phenotypes in Timothy syndrome. Nature 471, 230–234 (2011).

    CAS  PubMed  PubMed Central  Google Scholar 

  58. Paşca, S.P. et al. Using iPSC-derived neurons to uncover cellular phenotypes associated with Timothy syndrome. Nat. Med. 17, 1657–1662 (2011).

    PubMed  PubMed Central  Google Scholar 

  59. Krey, J.F. et al. Timothy syndrome is associated with activity-dependent dendritic retraction in rodent and human neurons. Nat. Neurosci. 16, 201–209 (2013).

    CAS  PubMed  PubMed Central  Google Scholar 

  60. Marini, C. et al. The genetics of Dravet syndrome. Epilepsia 52 (suppl. 2), 24–29 (2011).

    CAS  PubMed  Google Scholar 

  61. Ragona, F. et al. Cognitive development in Dravet syndrome: a retrospective, multicenter study of 26 patients. Epilepsia 52, 386–392 (2011).

    PubMed  Google Scholar 

  62. Yu, F.H. et al. Reduced sodium current in GABAergic interneurons in a mouse model of severe myoclonic epilepsy in infancy. Nat. Neurosci. 9, 1142–1149 (2006).

    CAS  PubMed  Google Scholar 

  63. Ogiwara, I. et al. Na(v)1.1 localizes to axons of parvalbumin-positive inhibitory interneurons: a circuit basis for epileptic seizures in mice carrying an Scn1a gene mutation. J. Neurosci. 27, 5903–5914 (2007).

    CAS  PubMed  PubMed Central  Google Scholar 

  64. Higurashi, N. et al. A human Dravet syndrome model from patient induced pluripotent stem cells. Mol. Brain 6, 19 (2013).

    CAS  PubMed  PubMed Central  Google Scholar 

  65. Jiao, J. et al. Modeling Dravet syndrome using induced pluripotent stem cells (iPSCs) and directly converted neurons. Hum. Mol. Genet. 22, 4241–4252 (2013).

    CAS  PubMed  Google Scholar 

  66. Liu, Y. et al. Dravet syndrome patient-derived neurons suggest a novel epilepsy mechanism. Ann. Neurol. 74, 128–139 (2013).

    CAS  PubMed  PubMed Central  Google Scholar 

  67. Mistry, A.M. et al. Strain- and age-dependent hippocampal neuron sodium currents correlate with epilepsy severity in Dravet syndrome mice. Neurobiol. Dis. 65, 1–11 (2014).

    CAS  PubMed  PubMed Central  Google Scholar 

  68. Leyser, M., Penna, P.S., de Almeida, A.C., Vasconcelos, M.M. & Nascimento, O.J. Revisiting epilepsy and the electroencephalogram patterns in Angelman syndrome. Neurol. Sci. 35, 701–705 (2014).

    PubMed  Google Scholar 

  69. Williams, C.A., Driscoll, D.J. & Dagli, A.I. Clinical and genetic aspects of Angelman syndrome. Genet. Med. 12, 385–395 (2010).

    CAS  PubMed  Google Scholar 

  70. Chamberlain, S.J. et al. Induced pluripotent stem cell models of the genomic imprinting disorders Angelman and Prader-Willi syndromes. Proc. Natl. Acad. Sci. USA 107, 17668–17673 (2010).

    CAS  PubMed  PubMed Central  Google Scholar 

  71. Ricciardi, S. et al. 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, 911–923 (2012).

    CAS  PubMed  PubMed Central  Google Scholar 

  72. Livide, G. et al. GluD1 is a common altered player in neuronal differentiation from both MECP2-mutated and CDKL5-mutated iPS cells. Eur. J. Hum. Genet. (2014).

  73. Southwell, D.G. et al. Interneurons from embryonic development to cell-based therapy. Science 344, 1240622 (2014).

    PubMed  PubMed Central  Google Scholar 

  74. Tyson, J.A. & Anderson, S.A. GABAergic interneuron transplants to study development and treat disease. Trends Neurosci. 37, 169–177 (2014).

    CAS  PubMed  PubMed Central  Google Scholar 

  75. Tanaka, D.H. & Nakajima, K. GABAergic interneuron migration and the evolution of the neocortex. Dev. Growth Differ. 54, 366–372 (2012).

    CAS  PubMed  Google Scholar 

  76. Guo, J. & Anton, E.S. Decision making during interneuron migration in the developing cerebral cortex. Trends Cell Biol. 24, 342–351 (2014).

    CAS  PubMed  PubMed Central  Google Scholar 

  77. Letinic, K., Zoncu, R. & Rakic, P. Origin of GABAergic neurons in the human neocortex. Nature 417, 645–649 (2002).

    CAS  PubMed  Google Scholar 

  78. Zecevic, N., Hu, F. & Jakovcevski, I. Interneurons in the developing human neocortex. Dev. Neurobiol. 71, 18–33 (2011).

    PubMed  PubMed Central  Google Scholar 

  79. Ma, T. et al. Subcortical origins of human and monkey neocortical interneurons. Nat. Neurosci. 16, 1588–1597 (2013).

    CAS  PubMed  Google Scholar 

  80. Hansen, D.V. et al. Non-epithelial stem cells and cortical interneuron production in the human ganglionic eminences. Nat. Neurosci. 16, 1576–1587 (2013).

    CAS  PubMed  PubMed Central  Google Scholar 

  81. Wichterle, H., Garcia-Verdugo, J.M., Herrera, D.G. & Alvarez-Buylla, A. Young neurons from medial ganglionic eminence disperse in adult and embryonic brain. Nat. Neurosci. 2, 461–466 (1999).

    CAS  PubMed  Google Scholar 

  82. Maroof, A.M., Brown, K., Shi, S.H., Studer, L. & Anderson, S.A. Prospective isolation of cortical interneuron precursors from mouse embryonic stem cells. J. Neurosci. 30, 4667–4675 (2010).

    CAS  PubMed  PubMed Central  Google Scholar 

  83. Danjo, T. et al. Subregional specification of embryonic stem cell-derived ventral telencephalic tissues by timed and combinatory treatment with extrinsic signals. J. Neurosci. 31, 1919–1933 (2011).

    CAS  PubMed  PubMed Central  Google Scholar 

  84. Au, E. et al. A modular gain-of-function approach to generate cortical interneuron subtypes from ES cells. Neuron 80, 1145–1158 (2013).

    CAS  PubMed  PubMed Central  Google Scholar 

  85. Maisano, X. et al. Differentiation and functional incorporation of embryonic stem cell-derived GABAergic interneurons in the dentate gyrus of mice with temporal lobe epilepsy. J. Neurosci. 32, 46–61 (2012).

    CAS  PubMed  PubMed Central  Google Scholar 

  86. Fertuzinhos, S. et al. Selective depletion of molecularly defined cortical interneurons in human holoprosencephaly with severe striatal hypoplasia. Cereb. Cortex 19, 2196–2207 (2009).

    PubMed  PubMed Central  Google Scholar 

  87. Maroof, A.M. et al. Directed differentiation and functional maturation of cortical interneurons from human embryonic stem cells. Cell Stem Cell 12, 559–572 (2013).

    CAS  PubMed  PubMed Central  Google Scholar 

  88. Nicholas, C.R. et al. Functional maturation of hPSC-derived forebrain interneurons requires an extended timeline and mimics human neural development. Cell Stem Cell 12, 573–586 (2013).

    CAS  PubMed  PubMed Central  Google Scholar 

  89. Liu, Y. et al. Medial ganglionic eminence-like cells derived from human embryonic stem cells correct learning and memory deficits. Nat. Biotechnol. 31, 440–447 (2013).

    PubMed  PubMed Central  Google Scholar 

  90. Kim, T.G. et al. Efficient specification of interneurons from human pluripotent stem cells by dorsoventral and rostrocaudal modulation. Stem Cells 32, 1789–1804 (2014).

    CAS  PubMed  PubMed Central  Google Scholar 

  91. Cunningham, M. et al. hPSC-derived maturing GABAergic interneurons ameliorate seizures and abnormal behavior in epileptic mice. Cell Stem Cell 15, 559–573 (2014).

    CAS  PubMed  PubMed Central  Google Scholar 

  92. Alvarez-Dolado, M. et al. Cortical inhibition modified by embryonic neural precursors grafted into the postnatal brain. J. Neurosci. 26, 7380–7389 (2006).

    CAS  PubMed  PubMed Central  Google Scholar 

  93. Zipancic, I., Calcagnotto, M.E., Piquer-Gil, M., Mello, L.E. & Alvarez-Dolado, M. Transplant of GABAergic precursors restores hippocampal inhibitory function in a mouse model of seizure susceptibility. Cell Transplant. 19, 549–564 (2010).

    CAS  PubMed  Google Scholar 

  94. Vierbuchen, T. et al. Direct conversion of fibroblasts to functional neurons by defined factors. Nature 463, 1035–1041 (2010).

    CAS  PubMed  PubMed Central  Google Scholar 

  95. Ring, K.L. et al. Direct reprogramming of mouse and human fibroblasts into multipotent neural stem cells with a single factor. Cell Stem Cell 11, 100–109 (2012).

    CAS  PubMed  PubMed Central  Google Scholar 

  96. Kim, H.S., Bernitz, J., Lee, D.F. & Lemischka, I.R. Genomic editing tools to model human diseases with isogenic pluripotent stem cells. Stem Cells Dev. 23, 2673–2686 (2014).

    CAS  PubMed  PubMed Central  Google Scholar 

  97. Halai, R. & Cooper, M.A. Using label-free screening technology to improve efficiency in drug discovery. Expert Opin. Drug Discov. 7, 123–131 (2012).

    CAS  PubMed  Google Scholar 

  98. Yu, D.X. et al. Modeling hippocampal neurogenesis using human pluripotent stem cells. Stem Cell Reports 2, 295–310 (2014).

    CAS  PubMed  PubMed Central  Google Scholar 

  99. Chen, C. et al. Role of astroglia in Down's syndrome revealed by patient-derived human-induced pluripotent stem cells. Nat. Commun. 5, 4430 (2014).

    CAS  PubMed  Google Scholar 

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Acknowledgements

The authors thank L. Isom and S. Barmada for comments on the manuscript; X. Du, G. Patino and Y. Liu for providing data for the figures; and the US National Institutes of Health (grants NS065450 and NS076916 to J.M.P. and grant MH066912 to S.A.A.) and Citizens United for Research in Epilepsy (to J.M.P.) for financial support.

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Parent, J., Anderson, S. Reprogramming patient-derived cells to study the epilepsies. Nat Neurosci 18, 360–366 (2015). https://doi.org/10.1038/nn.3944

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