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Opportunities and challenges of pluripotent stem cell neurodegenerative disease models

Nature Neuroscience volume 16, pages 780–789 (2013)Cite this article

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Abstract

Human neurodegenerative disorders are among the most difficult to study. In particular, the inability to readily obtain the faulty cell types most relevant to these diseases has impeded progress for decades. Recent advances in pluripotent stem cell technology now grant access to substantial quantities of disease-pertinent neurons both with and without predisposing mutations. While this suite of technologies has revolutionized the field of 'in vitro disease modeling', great care must be taken in their deployment if robust, durable discoveries are to be made. Here we review what we perceive to be several of the stumbling blocks in the use of stem cells for the study of neurological disease and offer strategies to overcome them.

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Figure 1: Variability amongst cohorts of pluripotent stem cells may lead to erroneous conclusions in disease modeling experiments driven by atypical cell lines.
Figure 2: The diversity of neuronal cultures derived from pluripotent stem cells can interfere with phenotypic observations.
Figure 3: Observation of neurons resistant to the disease being studied could allow meaningful comparisons between vulnerable and resistant neurons derived from control and patient pluripotent cell lines.

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References

  1. Kiskinis, E. & Eggan, K. Progress toward the clinical application of patient-specific pluripotent stem cells. J. Clin. Invest. 120, 51–59 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Wichterle, H., Lieberam, I. & Porter, J. Directed differentiation of embryonic stem cells into motor neurons. Cell 110, 385–397 (2002).

    Article  CAS  PubMed  Google Scholar 

  3. Zhang, S.-C., Wernig, M., Duncan, I.D., Brustle, O. & Thomson, J.A. In vitro differentiation of transplantable neural precursors from human embryonic stem cells. Nat. Biotechnol. 19, 1129–1133 (2001).

    Article  CAS  PubMed  Google Scholar 

  4. Murry, C.E. & Keller, G. Differentiation of embryonic stem cells to clinically relevant populations: lessons from embryonic development. Cell 132, 661–680 (2008).

    Article  CAS  PubMed  Google Scholar 

  5. Bellin, M., Marchetto, M.C., Gage, F.H. & Mummery, C.L. Induced pluripotent stem cells: the new patient? Nat. Rev. Mol. Cell Biol. 13, 713–726 (2012).

    Article  CAS  PubMed  Google Scholar 

  6. 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 

  7. 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).

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Liu, G.-H. et al. Progressive degeneration of human neural stem cells caused by pathogenic LRRK2. Nature 491, 603–607 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Han, S.S.W., Williams, L.A. & Eggan, K.C. Constructing and deconstructing stem cell models of neurological disease. Neuron 70, 626–644 (2011).

    Article  CAS  PubMed  Google Scholar 

  11. Yagi, T. et al. Modeling familial Alzheimer's disease with induced pluripotent stem cells. Hum. Mol. Genet. 20, 4530–4539 (2011).

    Article  CAS  PubMed  Google Scholar 

  12. Sánchez-Danés, A. et al. Disease-specific phenotypes in dopamine neurons from human iPS-based models of genetic and sporadic Parkinson's disease. EMBO Mol. Med. 80, 380–395 (2012).

    Article  CAS  Google Scholar 

  13. Jeon, I. et al. Neuronal properties, in vivo effects, and pathology of a Huntington's disease patient-derived induced pluripotent stem cells. Stem Cells 30, 2054–2062 (2012).

    Article  CAS  PubMed  Google Scholar 

  14. Ebert, A.D. et al. Induced pluripotent stem cells from a spinal muscular atrophy patient. Nature 457, 277–280 (2009).

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Brennand, K.J. et al. Modelling schizophrenia using human induced pluripotent stem cells. Nature 473, 221–225 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Boulting, G.L. et al. A functionally characterized test set of human induced pluripotent stem cells. Nat. Biotechnol. 29, 279–286 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Xu, C. et al. Feeder-free growth of undifferentiated human embryonic stem cells. Nat. Biotechnol. 19, 971–974 (2001).

    Article  CAS  PubMed  Google Scholar 

  20. Chen, A.E. et al. Optimal timing of inner cell mass isolation increases the efficiency of human embryonic stem cell derivation and allows generation of sibling cell lines. Cell Stem Cell 4, 103–106 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  22. Di Giorgio, F.P., Boulting, G., Bobrowicz, S. & Eggan, K. Human embryonic stem cell-derived motor neurons are sensitive to the toxic effect of glial cells carrying an ALS-causing mutation. Cell Stem Cell 3, 637–648 (2008).

    Article  CAS  PubMed  Google Scholar 

  23. Marchetto, M.C.N. et al. Non-cell-autonomous effect of human SOD1 G37R astrocytes on motor neurons derived from human embryonic stem cells. Cell Stem Cell 3, 649–657 (2008).

    Article  CAS  PubMed  Google Scholar 

  24. Verlinsky, Y. et al. Human embryonic stem cell lines with genetic disorders. Reprod. Biomed. Online 10, 105–110 (2005).

    Article  CAS  PubMed  Google Scholar 

  25. Mateizel, I. et al. Derivation of human embryonic stem cell lines from embryos obtained after IVF and after PGD for monogenic disorders. Hum. Reprod. 21, 503–511 (2006).

    Article  CAS  PubMed  Google Scholar 

  26. Yu, J. et al. Induced pluripotent stem cell lines derived from human somatic cells. Science 318, 1917–1920 (2007).

    Article  CAS  PubMed  Google Scholar 

  27. 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).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. 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).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Ohi, Y. et al. Incomplete DNA methylation underlies a transcriptional memory of somatic cells in human iPS cells. Nat. Cell Biol. 13, 541–549 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Daley, G.Q. et al. Broader implications of defining standards for the pluripotency of iPSCs. Cell Stem Cell 4, 200–201 (2009).

    Article  CAS  PubMed  Google Scholar 

  33. Lister, R. et al. Hotspots of aberrant epigenomic reprogramming in human induced pluripotent stem cells. Nature 471, 68–73 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Marchetto, M.C.N. et al. Transcriptional signature and memory retention of human-induced pluripotent stem cells. PLoS ONE 4, e7076 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Polo, J.M. et al. Cell type of origin influences the molecular and functional properties of mouse induced pluripotent stem cells. Nat. Biotechnol. 28, 848–855 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Silva, S.S., Rowntree, R.K., Mekhoubad, S. & Lee, J.T. X-chromosome inactivation and epigenetic fluidity in human embryonic stem cells. Proc. Natl. Acad. Sci. USA 105, 4820–4825 (2008).

    Article  PubMed  PubMed Central  Google Scholar 

  37. Osafune, K. et al. Marked differences in differentiation propensity among human embryonic stem cell lines. Nat. Biotechnol. 26, 313–315 (2008).

    Article  CAS  PubMed  Google Scholar 

  38. Hu, B., Weick, J., Yu, J. & Ma, L. Neural differentiation of human induced pluripotent stem cells follows developmental principles but with variable potency. Proc. Natl. Acad. Sci. USA 107, 4335–4340 (2010).

    Article  PubMed  PubMed Central  Google Scholar 

  39. Kondo, T. et al. Modeling Alzheimer's disease with iPSCs reveals stress phenotypes associated with intracellular Aβ and differential drug responsiveness. Cell Stem Cell 12, 487–496 (2013).

    Article  CAS  PubMed  Google Scholar 

  40. Huntington's Consortium. Induced pluripotent stem cells from patients with Huntington's disease show CAG-repeat-expansion-associated phenotypes. Cell Stem Cell 11, 264–278 (2012).

  41. Chang, T. et al. Brief report: phenotypic rescue of induced pluripotent stem cell-derived motoneurons of a spinal muscular atrophy patient. Stem Cells 29, 2090–2093 (2011).

    Article  CAS  PubMed  Google Scholar 

  42. Soldner, F. et al. Generation of isogenic pluripotent stem cells differing exclusively at two early onset Parkinson point mutations. Cell 146, 318–331 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. An, M.C. et al. Genetic correction of Huntington's disease phenotypes in induced pluripotent stem cells. Cell Stem Cell 11, 253–263 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Khan, I.F., Hirata, R.K. & Russell, D.W. AAV-mediated gene targeting methods for human cells. Nat. Protoc. 6, 482–501 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Aizawa, E. et al. Efficient and accurate homologous recombination in hESCs and hiPSCs using helper-dependent adenoviral vectors. Mol. Ther. 20, 424–431 (2012).

    Article  CAS  PubMed  Google Scholar 

  46. Andersen, M.S., Sørensen, C.B., Bolund, L. & Jensen, T.G. Mechanisms underlying targeted gene correction using chimeric RNA/DNA and single-stranded DNA oligonucleotides. J. Mol. Med. 80, 770–781 (2002).

    Article  CAS  PubMed  Google Scholar 

  47. Zou, J. et al. Gene targeting of a disease-related gene in human induced pluripotent stem and embryonic stem cells. Cell Stem Cell 5, 97–110 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Mali, P. et al. RNA-guided human genome engineering via Cas9. Science 339, 823–826 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  49. Hockemeyer, D. et al. Genetic engineering of human pluripotent cells using TALE nucleases. Nat. Biotechnol. 29, 731–734 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. Urnov, F.D., Rebar, E.J., Holmes, M.C., Zhang, H.S. & Gregory, P.D. Genome editing with engineered zinc finger nucleases. Nat. Rev. Genet. 11, 636–646 (2010).

    Article  CAS  PubMed  Google Scholar 

  51. Reinhardt, P. et al. Genetic correction of a LRRK2 mutation in human iPSCs links Parkinsonian neurodegeneration to ERK-dependent changes in gene expression. Cell Stem Cell 12, 354–367 (2013).

    Article  CAS  PubMed  Google Scholar 

  52. Corti, S. et al. Genetic correction of human induced pluripotent stem cells from patients with spinal muscular atrophy. Sci. Transl. Med. 4, 165ra162 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  53. Lombardo, A. et al. Site-specific integration and tailoring of cassette design for sustainable gene transfer. Nat. Methods 8, 861–869 (2011).

    Article  CAS  PubMed  Google Scholar 

  54. Yusa, K. et al. Targeted gene correction of α1-antitrypsin deficiency in induced pluripotent stem cells. Nature 478, 391–394 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  55. Qiurong, D. et al. A TALEN genome-editing system for generating human stem cell-based disease models. Cell Stem Cell 12, 238–251 (2012).

    Google Scholar 

  56. Kanning, K.C., Kaplan, A. & Henderson, C.E. Motor neuron diversity in development and disease. Annu. Rev. Neurosci. 33, 409–440 (2010).

    Article  CAS  PubMed  Google Scholar 

  57. Chambers, S.M. et al. Combined small-molecule inhibition accelerates developmental timing and converts human pluripotent stem cells into nociceptors. Nat. Biotechnol. 30, 715–720 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  58. Wataya, T. et al. Minimization of exogenous signals in ES cell culture induces rostral hypothalamic differentiation. Proc. Natl. Acad. Sci. USA 105, 11796–11801 (2008).

    Article  PubMed  PubMed Central  Google Scholar 

  59. Kriks, S. et al. Dopamine neurons derived from human ES cells efficiently engraft in animal models of Parkinson's disease. Nature 418, 50–56 (2011).

    Google Scholar 

  60. Yuan, S.H. et al. Cell-surface marker signatures for the isolation of neural stem cells, glia and neurons derived from human pluripotent stem cells. PLoS ONE 6, e17540 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  61. Di Giorgio, F.P., Carrasco, M., Siao, M., Maniatis, T. & Eggan, K. Non-cell autonomous effect of glia on motor neurons in an embryonic stem cell-based ALS model. Nat. Neurosci. 10, 608–614 (2007).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  62. Lobsiger, C.S. & Cleveland, D.W. Glial cells as intrinsic components of non-cell-autonomous neurodegenerative disease. Nat. Neurosci. 10, 1355–1360 (2007).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  63. Amoroso, M.W. et al. Accelerated high-yield generation of limb-innervating motor neurons from human stem cells. J. Neurosci. 33, 574–586 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  64. Bilican, B. et al. Mutant induced pluripotent stem cell lines recapitulate aspects of TDP-43 proteinopathies and reveal cell-specific vulnerability. Proc. Natl. Acad. Sci. USA 109, 5803–5808 (2012).

    Article  PubMed  PubMed Central  Google Scholar 

  65. Hockemeyer, D. et al. Efficient targeting of expressed and silent genes in human ESCs and iPSCs using zinc-finger nucleases. Nat. Biotechnol. 27, 851–857 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  66. Sergent-Tanguy, S., Chagneau, C., Neveu, I. & Naveilhan, P. Fluorescent activated cell sorting (FACS): a rapid and reliable method to estimate the number of neurons in a mixed population. J. Neurosci. Methods 129, 73–79 (2003).

    Article  PubMed  Google Scholar 

  67. Vodyanik, M.A., Thomson, J.A. & Slukvin, I.I. Leukosialin (CD43) defines hematopoietic progenitors in human embryonic stem cell differentiation cultures. Blood 108, 2095–2105 (2006).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  68. Singh Roy, N. et al. Enhancer-specified GFP-based FACS purification of human spinal motor neurons from embryonic stem cells. Exp. Neurol. 196, 224–234 (2005).

    Article  CAS  PubMed  Google Scholar 

  69. Molyneaux, B.J., Arlotta, P., Menezes, J.R.L. & Macklis, J.D. Neuronal subtype specification in the cerebral cortex. Nat. Rev. Neurosci. 8, 427–437 (2007).

    Article  CAS  PubMed  Google Scholar 

  70. Dawson, T.M. & Dawson, V.L. Neuroprotective and neurorestorative strategies for Parkinson's disease. Nat. Neurosci. 5, 1058–1061 (2002).

    Article  CAS  PubMed  Google Scholar 

  71. Nunes, I., Tovmasian, L.T., Silva, R.M., Burke, R.E. & Goff, S.P. Pitx3 is required for development of substantia nigra dopaminergic neurons. Proc. Natl. Acad. Sci. USA 100, 4245–4250 (2003).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  72. von Steyern, F.V. et al. The homeodomain transcription factors Islet 1 and HB9 are expressed in adult alpha and gamma motoneurons identified by selective retrograde tracing. Eur. J. Neurosci. 11, 2093–2102 (1999).

    Article  Google Scholar 

  73. Takazawa, T. et al. Maturation of spinal motor neurons derived from human embryonic stem cells. PLoS ONE 7, e40154 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  74. Kim, J.E. et al. Investigating synapse formation and function using human pluripotent stem cell-derived neurons. Proc. Natl. Acad. Sci. USA 108, 3005–3010 (2011).

    Article  PubMed  PubMed Central  Google Scholar 

  75. Shi, Y., Kirwan, P., Smith, J., Robinson, H.P.C. & Livesey, F.J. Human cerebral cortex development from pluripotent stem cells to functional excitatory synapses. Nat. Neurosci. 15, 477–486 (2012).

    Article  CAS  PubMed  Google Scholar 

  76. Delaloy, C. et al. MicroRNA-9 coordinates proliferation and migration of human embryonic stem cell-derived neural progenitors. Cell Stem Cell 6, 323–335 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  77. Juurlink, B.H.J. & Walz, W. Neural cell culture techniques. Neuromethods 33, 53–102 (1998).

    Google Scholar 

  78. Pang, Z.P. et al. Induction of human neuronal cells by defined transcription factors. Nature 476, 220–223 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  79. Son, E.Y. et al. Conversion of mouse and human fibroblasts into functional spinal motor neurons. Cell Stem Cell 9, 205–218 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  80. Hester, M. et al. Rapid and efficient generation of functional motor neurons from human pluripotent stem cells using gene delivered transcription factor codes. Mol. Ther. 19, 1905–1912 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  81. Christopherson, K.S. et al. Thrombospondins are astrocyte-secreted proteins that promote CNS synaptogenesis. Cell 120, 421–433 (2005).

    Article  CAS  PubMed  Google Scholar 

  82. Keller, J.N., Huang, F. & Markesbery, W. Decreased levels of proteasome activity and proteasome expression in aging spinal cord. Neuroscience 98, 149–156 (2000).

    Article  CAS  PubMed  Google Scholar 

  83. Erraji-Benchekroun, L. et al. Molecular aging in human prefrontal cortex is selective and continuous throughout adult life. Biol. Psychiatry 57, 549–558 (2005).

    Article  CAS  PubMed  Google Scholar 

  84. Cheung, I. et al. Developmental regulation and individual differences of neuronal H3K4me3 epigenomes in the prefrontal cortex. Proc. Natl. Acad. Sci. USA 107, 8824–8829 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  85. Wong, E. & Cuervo, A.M. Autophagy gone awry in neurodegenerative diseases. Nat. Neurosci. 13, 805–811 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  86. Matus, S., Glimcher, L.H. & Hetz, C. Protein folding stress in neurodegenerative diseases: a glimpse into the ER. Curr. Opin. Cell Biol. 23, 239–252 (2011).

    Article  CAS  PubMed  Google Scholar 

  87. Alegre-Abarrategui, J., Ansorge, O., Esiri, M. & Wade-Martins, R. LRRK2 is a component of granular alpha-synuclein pathology in the brainstem of Parkinson's disease. Neuropathol. Appl. Neurobiol. 34, 272–283 (2008).

    Article  CAS  PubMed  Google Scholar 

  88. Shi, Y. et al. A human stem cell model of early Alzheimer's disease pathology in Down syndrome. Sci. Transl. Med. 4, 124ra129 (2012).

    Google Scholar 

  89. Egawa, N. et al. Drug screening for ALS using patient-specific induced pluripotent stem cells. Sci. Transl. Med. 4, 145ra104 (2012).

  90. Cooper, O. et al. Pharmacological rescue of mitochondrial deficits in iPSC-derived neural cells from patients with familial Parkinson's disease. Sci. Transl. Med. 4, 141ra190 (2012).

    Article  CAS  Google Scholar 

  91. Koch, P. et al. Excitation-induced ataxin-3 aggregation in neurons from patients with Machado-Joseph disease. Nature. 480, 543–546 (2011).

    Article  CAS  PubMed  Google Scholar 

  92. Nguyen, H.N. et al. LRRK2 mutant iPSC-derived DA neurons demonstrate increased susceptibility to oxidative stress. Cell Stem Cell 8, 267–280 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  93. Fabian, M.A. et al. A small molecule–kinase interaction map for clinical kinase inhibitors. Nat. Biotechnol. 23, 329–336 (2005).

    Article  CAS  PubMed  Google Scholar 

  94. Double, K.L., Reyes, S., Werry, E. & Halliday, G. Selective cell death in neurodegeneration: why are some neurons spared in vulnerable regions? Prog. Neurobiol. 92, 316–329 (2010).

    Article  CAS  PubMed  Google Scholar 

  95. Saxena, S., Cabuy, E. & Caroni, P. A role for motoneuron subtype–selective ER stress in disease manifestations of FALS mice. Nat. Neurosci. 12, 627–636 (2009).

    Article  CAS  PubMed  Google Scholar 

  96. Rosen, D.R. et al. Mutations in Cu/Zn superoxide dismutase gene are associated with familial amyotrophic lateral sclerosis. Nature 362, 59–62 (1993).

    Article  CAS  PubMed  Google Scholar 

  97. Brockington, A. et al. Unravelling the enigma of selective vulnerability in neurodegeneration: motor neurons resistant to degeneration in ALS show distinct gene expression characteristics and decreased susceptibility to excitotoxicity. Acta Neuropathol. 125, 95–109 (2013).

    Article  CAS  PubMed  Google Scholar 

  98. Renton, A.E. et al. A hexanucleotide repeat expansion in C9ORF72 is the cause of chromosome 9p21-linked ALS-FTD. Neuron 72, 257–268 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  99. Seeley, W.W. et al. Early frontotemporal dementia targets neurons unique to apes and humans. Ann. Neurol. 60, 660–667 (2006).

    Article  PubMed  Google Scholar 

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Acknowledgements

We would like to thank S. Dutra, L. Williams, F. Merkle and J. Klim for discussions and comments on the manuscript.

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  1. Department of Molecular and Cellular Biology, Harvard University, Cambridge, Massachusetts, USA

    Jackson Sandoe

  2. Department of Stem Cell and Regenerative Biology, Harvard Stem Cell Institute, Harvard University, Cambridge, Massachusetts, USA

    Jackson Sandoe & Kevin Eggan

  3. The Howard Hughes Medical Institute, Harvard University, Cambridge, Massachusetts, USA

    Kevin Eggan

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Correspondence to Kevin Eggan.

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K.E. is an author on a patent describing the lineage scorecard.

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Sandoe, J., Eggan, K. Opportunities and challenges of pluripotent stem cell neurodegenerative disease models. Nat Neurosci 16, 780–789 (2013). https://doi.org/10.1038/nn.3425

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