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GABAergic Neurons from Mouse Embryonic Stem Cells Possess Functional Properties of Striatal Neurons In Vitro, and Develop into Striatal Neurons In Vivo in a Mouse Model of Huntington’s Disease

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Abstract

Huntington’s disease (HD) is a neurodegenerative disease where GABAergic medium spiny neurons (MSNs) in the striatum degenerate. Embryonic stem cell-derived neural transplantation may provide an appropriate therapy for HD. Here we aimed to develop a suitable protocol to obtain a high percentage of functional GABAergic neurons from mouse embryonic stem cells (mESCs), and then tested their differentiation potential in vivo. The monolayer method was compared with the embryoid body and five stage method for its efficiency in generating GABAergic neurons from mESCs. All three methods yielded a similar percentage of GABAergic neurons from mESCs. Monolayer method-derived GABAergic neurons expressed the MSN marker dopamine- and cyclic AMP-regulated phosphoprotein (DARPP32). The pluripotent stem cell population could be eliminated in vitro by treating cells with puromycin and retinoic acid. Using patch-clamp recordings, the functional properties of GABAergic neurons derived from mESCs were compared to GABAergic neurons derived from primary lateral ganglionic eminence. Both types of neurons showed active membrane properties (voltage-gated Na+ and K+ currents, Na+-dependent action potentials, and spontaneous postsynaptic currents) and possessed functional glutamatergic receptors and transporters. mESC-derived neural progenitors were transplanted into a mouse model of HD. Grafted cells differentiated to mature neurons expressing glutamate decarboxylase, dopamine type 1 receptors, and DARPP32. Also, neural precursors and dividing populations were found in the grafts. In summary, mESCs are able to differentiate efficiently into functional GABAergic neurons using defined in vitro conditions, and these survive and differentiate following grafting to a mouse model of HD.

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References

  1. Deng, Y. P., Albin, R. L., Penney, J. B., Young, A. B., Anderson, K. D., & Reiner, A. (2004). Differential loss of striatal projection systems in Huntington’s disease: A quantitative immunohistochemical study. Journal of Chemical Neuroanatomy, 27(3), 143–164.

    Article  PubMed  CAS  Google Scholar 

  2. Reiner, A., Albin, R. L., Anderson, K. D., D’Amato, C. J., Penney, J. B., & Young, A. B. (1988). Differential loss of striatal projection neurons in Huntington disease. Proceedings of the National Academy of Sciences of the United States of America, 85, 5733–5737.

    Article  PubMed  CAS  Google Scholar 

  3. Martin, G. R. (1981). Isolation of a pluripotent cell line from early mouse embryos cultured in medium conditioned by teratocarcinoma stem cells. Proceedings of the National Academy of Sciences of the United States of America, 78(12), 7634–7638.

    Article  PubMed  CAS  Google Scholar 

  4. Ying, Q. L., Stavridis, M., Griffiths, D., Li, M., & Smith, A. (2003). Conversion of embryonic stem cells into neuroectodermal precursors in adherent monoculture. Nature Biotechnology, 21(2), 183–186.

    Article  PubMed  CAS  Google Scholar 

  5. Bain, G., Kitchens, D., Yao, M., Huettner, J. E., & Gottlieb, D. I. (1995). Embryonic stem cells express neuronal properties in vitro. Developmental Biology, 168(2), 342–357.

    Article  PubMed  CAS  Google Scholar 

  6. Fraichard, A., Chassande, O., Bilbaut, G., Dehay, C., Savatier, P., & Samarut, J. (1995). In vitro differentiation of embryonic stem cells into glial cells and functional neurons. Journal of Cell Science, 108(Pt 10), 3181–3188.

    PubMed  CAS  Google Scholar 

  7. Lang, R. J., Haynes, J. M., Kelly, J., et al. (2004). Electrical and neurotransmitter activity of mature neurons derived from mouse embryonic stem cells by Sox-1 lineage selection and directed differentiation. European Journal Neuroscience, 20(12), 3209–3221.

    Article  CAS  Google Scholar 

  8. Strubing, C., Ahnert-Hilger, G., Shan, J., Wiedenmann, B., Hescheler, J., & Wobus, A. M. (1995). Differentiation of pluripotent embryonic stem cells into the neuronal lineage in vitro gives rise to mature inhibitory and excitatory neurons. Mechanisms of Development, 53(2), 275–287.

    Article  PubMed  CAS  Google Scholar 

  9. Okabe, S., Forsberg-Nilsson, K., Spiro, A. C., Segal, M., & McKay, R. D. (1996). Development of neuronal precursor cells and functional postmitotic neurons from embryonic stem cells in vitro. Mechanisms of Development, 59(1), 89–102.

    Article  PubMed  CAS  Google Scholar 

  10. Westmoreland, J. J., Hancock, C. R., & Condie, B. G. (2001). Neuronal development of embryonic stem cells: A model of GABAergic neuron differentiation. Biochemical and Biophysical Research Communications, 284(3), 674–680.

    Article  PubMed  CAS  Google Scholar 

  11. Schubert, D., Heinemann, S., Carlisle, W., et al. (1974). Clonal cell lines from the rat central nervous system. Nature, 249(454), 224–227.

    Article  PubMed  CAS  Google Scholar 

  12. Ryder, E. F., Snyder, E. Y., & Cepko, C. L. (1990). Establishment and characterization of multipotent neural cell lines using retrovirus vector-mediated oncogene transfer. Journal of Neurobiology, 21(2), 356–375.

    Article  PubMed  CAS  Google Scholar 

  13. Sucher, N. J., Brose, N., Deitcher, D. L., et al. (1993). Expression of endogenous NMDAR1 transcripts without receptor protein suggests post-transcriptional control in PC12 cells. Journal of Biological Chemistry, 268(30), 22299–22304.

    PubMed  CAS  Google Scholar 

  14. Hales, T. G., & Tyndale, R. F. (1994). Few cell lines with GABAA mRNAs have functional receptors. Journal of Neuroscience, 14(9), 5429–5436.

    PubMed  CAS  Google Scholar 

  15. Dihne, M., Bernreuther, C., Hagel, C., Wesche, K.O., Schachner, M. (2006). Embryonic stem cell-derived neuronally committed precursor cells with reduced teratoma formation after transplantation into the lesioned adult mouse brain. SC. 24(6), 1458–1466.

  16. Bernreuther, C., Dihne, M., Johann, V., et al. (2006). Neural cell adhesion molecule L1-transfected embryonic stem cells promote functional recovery after excitotoxic lesion of the mouse striatum. Journal of Neuroscience, 26(45), 11532–11539.

    Article  PubMed  CAS  Google Scholar 

  17. Hargus, G., Cui, Y., Schmid, J.S., et al. (2008). Tenascin-R promotes neuronal differentiation of embryonic stem cells and recruitment of host-derived neural precursor cells after excitotoxic lesion of the mouse striatum. SC. 26(8),1973–1984.

  18. Aubry, L., Bugi, A., Lefort, N., Rousseau, F., Peschanski, M., & Perrier, A. L. (2008). Striatal progenitors derived from human ES cells mature into DARPP32 neurons in vitro and in quinolinic acid-lesioned rats. Proceedings of the National Academy of Sciences of the United States of America, 105(43), 16707–16712.

    Article  PubMed  CAS  Google Scholar 

  19. Nasonkin, I., Mahairaki, V., Xu, L., et al. (2009). Long-term, stable differentiation of human embryonic stem cell-derived neural precursors grafted into the adult mammalian neostriatum. SC. 27(10), 2414–2426.

  20. Aubert, J., Stavridis, M. P., Tweedie, S., et al. (2003). Screening for mammalian neural genes via fluorescence-activated cell sorter purification of neural precursors from Sox1-gfp knock-in mice. Proceedings of the National Academy of Sciences of the United States of America, 100(Suppl 1), 11836–11841.

    Article  PubMed  CAS  Google Scholar 

  21. Lee, S. H., Lumelsky, N., Studer, L., Auerbach, J. M., & McKay, R. D. (2000). Efficient generation of midbrain and hindbrain neurons from mouse embryonic stem cells. Nature Biotechnology, 18(6), 675–679.

    Article  PubMed  CAS  Google Scholar 

  22. Nowak, L., Bregestovski, P., Ascher, P., Herbet, A., & Prochiantz, A. (1984). Magnesium gates glutamate-activated channels in mouse central neurones. Nature, 307(5950), 462–465.

    Article  PubMed  CAS  Google Scholar 

  23. Dinsmore, J., Ratliff, J., Deacon, T., et al. (1996). Embryonic stem cells differentiated in vitro as a novel source of cells for transplantation. Cell Transplantation, 5(2), 131–143.

    Article  PubMed  CAS  Google Scholar 

  24. Chatzi, C., Scott, R. H., Pu, J., et al. (2009). Derivation of homogeneous GABAergic neurons from mouse embryonic stem cells. Experimental Neurology, 217(2), 407–416.

    Article  PubMed  CAS  Google Scholar 

  25. Spiliotopoulos, D., Goffredo, D., Conti, L., et al. (2009). An optimized experimental strategy for efficient conversion of embryonic stem (ES)-derived mouse neural stem (NS) cells into a nearly homogeneous mature neuronal population. Neurobiology of Disease, 34(2), 320–331.

    Article  PubMed  CAS  Google Scholar 

  26. Ouimet, C. C., Miller, P. E., Hemmings, H. C., Walaas, S. I., & Greengard, P. (1984). DARPP-32, a dopamine- and adenosine-3′:5′-monophosphate-regulated phosphoprotein enriched in dopamine-innervated brain regions. Journal of Neuroscience, 4, 111–124.

    PubMed  CAS  Google Scholar 

  27. Anderson, K. D., & Reiner, A. (1991). Immunohistochemical localization of DARPP-32 in striatal projection neurons and striatal interneurons: Implications for the localization of D1-like dopamine receptors on different types of striatal neurons. Brain Research, 568(1–2), 235–243.

    Article  PubMed  CAS  Google Scholar 

  28. Aizman, O., Brismar, H., Uhlen, P., et al. (2000). Anatomical and physiological evidence for D1 and D2 dopamine receptor colocalization in neostriatal neurons. Nature Neuroscience, 3(3), 226–230.

    Article  PubMed  CAS  Google Scholar 

  29. Greengard, P., Nairn, A. C., Girault, J. A., et al. (1998). The DARPP-32/protein phosphatase-1 cascade: A model for signal integration. Brain Research Brain Research Reviews, 26(2–3), 274–284.

    Article  PubMed  CAS  Google Scholar 

  30. Ivkovic, S., & Ehrlich, M. E. (1999). Expression of the striatal DARPP-32/ARPP-21 phenotype in GABAergic neurons requires neurotrophins in vivo and in vitro. Journal of Neuroscience, 19(13), 5409–5419.

    PubMed  CAS  Google Scholar 

  31. Kawaguchi, Y. (1993). Physiological, morphological, and histochemical characterization of three classes of interneurons in rat neostriatum. Journal of Neuroscience, 13(11), 4908–4923.

    PubMed  CAS  Google Scholar 

  32. Bracci, E., Centonze, D., Bernardi, G., & Calabresi, P. (2003). Voltage-dependent membrane potential oscillations of rat striatal fast-spiking interneurons. Journal of Physiology, 549(Pt 1), 121–130.

    Article  PubMed  CAS  Google Scholar 

  33. Fricker-Gates, R. A., White, A., Gates, M. A., & Dunnett, S. B. (2004). Striatal neurons in striatal grafts are derived from both post-mitotic cells and dividing progenitors. European Journal of Neuroscience, 19(3), 513–520.

    Article  PubMed  Google Scholar 

  34. Kawaguchi, Y., Wilson, C. J., & Emson, P. C. (1989). Intracellular recording of identified neostriatal patch and matrix spiny cells in a slice preparation preserving cortical inputs. Journal of Neurophysiology, 62(5), 1052–1068.

    PubMed  CAS  Google Scholar 

  35. Tepper, J. M., & Trent, F. (1993). In vivo studies of the postnatal development of rat neostriatal neurons. Progress in Brain Research, 99, 35–50.

    Article  PubMed  CAS  Google Scholar 

  36. Tepper, J. M., Sharpe, N. A., Koos, T. Z., & Trent, F. (1998). Postnatal development of the rat neostriatum: Electrophysiological, light- and electron-microscopic studies. Developmental Neuroscience, 20(2–3), 125–145.

    Article  PubMed  CAS  Google Scholar 

  37. Finley, M. F., Kulkarni, N., & Huettner, J. E. (1996). Synapse formation and establishment of neuronal polarity by P19 embryonic carcinoma cells and embryonic stem cells. Journal of Neuroscience, 16(3), 1056–1065.

    PubMed  CAS  Google Scholar 

  38. Li, M., Pevny, L., Lovell-Badge, R., & Smith, A. (1998). Generation of purified neural precursors from embryonic stem cells by lineage selection. Current Biology, 8(17), 971–974.

    Article  PubMed  CAS  Google Scholar 

  39. Conti, L., Pollard, S. M., Gorba, T., et al. (2005). Niche-independent symmetrical self-renewal of a mammalian tissue stem cell. PLoS Biology, 3(9), e283.

    Article  PubMed  Google Scholar 

  40. Yoshizaki, T., Inaji, M., Kouike, H., et al. (2004). Isolation and transplantation of dopaminergic neurons generated from mouse embryonic stem cells. Neuroscience Letters, 363(1), 33–37.

    Article  PubMed  CAS  Google Scholar 

  41. Fukuda, H., Takahashi, J., Watanabe, K., et al. (2006). Fluorescence-activated cell sorting-based purification of embryonic stem cell-derived neural precursors averts tumor formation after transplantation. SC. 24(3),763–771.

    Google Scholar 

  42. Chung, S., Shin, B. S., Hedlund, E., et al. (2006). Genetic selection of sox1GFP-expressing neural precursors removes residual tumorigenic pluripotent stem cells and attenuates tumor formation after transplantation. Journal of Neurochemistry, 97(5), 1467–1480.

    Article  PubMed  CAS  Google Scholar 

  43. Manthorpe, M., Nieto-Sampedro, M., Skaper, S. D., et al. (1983). Neuronotrophic activity in brain wounds of the developing rat. Correlation with implant survival in the wound cavity. Brain Research, 267(1), 47–56.

    Article  PubMed  CAS  Google Scholar 

  44. Nieto-Sampedro, M., Manthrope, M., Barbin, G., Varon, S., & Cotman, C. W. (1983). Injury-induced neuronotrophic activity in adult rat brain: Correlation with survival of delayed implants in the wound cavity. Journal of Neuroscience, 3, 2219–2229.

    PubMed  CAS  Google Scholar 

  45. Needels, D. L., Nieto-Sampedro, M., Whittemore, S. R., & Cotman, C. W. (1985). Neuronotrophic activity for ciliary ganglion neurons. Induction following injury to the brain of neonatal, adult, and aged rats. Brain Research, 350(1–2), 275–284.

    PubMed  CAS  Google Scholar 

  46. Gage, F.H., Björklund, A. (1986). Enhanced graft survival in the hippocampus following selective denervation. Nsci. 17, 89–98.

    Google Scholar 

  47. Watts, C., & Dunnett, S. B. (1998). Effects of severity of host striatal damage on the morphological development of intrastriatal transplants in a rodent model of Huntington’s disease: Implications for timing of surgical development. Journal of Neurosurgery, 89, 367–374.

    Article  Google Scholar 

  48. Curtis, M. A., Penney, E. B., Pearson, A. G., et al. (2003). Increased cell proliferation and neurogenesis in the adult human Huntington’s disease brain. Proceedings of the National Academy of Sciences of the United States of America, 100(15), 9023–9027.

    Article  PubMed  CAS  Google Scholar 

  49. Tattersfield, A.S., Croon, R.J., Liu, Y.W., Kells, A.P., Faull, R.L., Connor, B. (2004). Neurogenesis in the striatum of the quinolinic acid lesion model of Huntington’s disease. Nsci. 127(2), 319–332.

    Google Scholar 

  50. Wang, Y., Sheen, V. L., & Macklis, J. D. (1998). Cortical interneurons upregulate neurotrophins in vivo in response to targeted apoptotic degeneration of neighboring pyramidal neurons. Experimental Neurology, 154(2), 389–402.

    Article  PubMed  CAS  Google Scholar 

  51. McKeon, R. J., Schreiber, R. C., Rudge, J. S., & Silver, J. (1991). Reduction of neurite outgrowth in a model of glial scarring following CNS injury is correlated with the expression of inhibitory molecules on reactive astrocytes. Journal of Neuroscience, 11(11), 3398–3411.

    PubMed  CAS  Google Scholar 

  52. Lundberg, C., Winkler, C., Whittemore, S. R., & Björklund, A. (1996). Conditionally immortalised neural progenitor cells grafted to the striatum exhibit site-specific neuronal differentiation and establish connections with the host globus pallidus. Neurobiology of Disease, 3, 33–50.

    Article  PubMed  CAS  Google Scholar 

  53. Faijerson, J., Tinsley, R. B., Aprico, K., et al. (2006). Reactive astrogliosis induces astrocytic differentiation of adult neural stem/progenitor cells in vitro. Journal of Neuroscience Research, 84(7), 1415–1424.

    Article  PubMed  CAS  Google Scholar 

  54. Joannides, A.J., Webber, D.J., Raineteau, O., et al. (2007). Environmental signals regulate lineage choice and temporal maturation of neural stem cells from human embryonic stem cells. B. 130(Pt 5), 1263–1275.

  55. Jensen, J. B., Bjorklund, A., & Parmar, M. (2004). Striatal neuron differentiation from neurosphere-expanded progenitors depends on Gsh2 expression. Journal of Neuroscience, 24(31), 6958–6967.

    Article  PubMed  CAS  Google Scholar 

  56. Dobrossy, M. D., & Dunnett, S. B. (2006). Morphological and cellular changes within embryonic striatal grafts associated with enriched environment and involuntary exercise. European Journal of Neuroscience, 24(11), 3223–3233.

    Article  PubMed  Google Scholar 

  57. Fricker-Gates, R. A., Winkler, C., Kirik, D., Rosenblad, C., Carpenter, M. K., & Björklund, A. (2000). EGF infusion stimulates the proliferation and migration of embryonic progenitor cells transplanted in the adult rat striatum. Experimental Neurology, 165(2), 237–247.

    Article  PubMed  CAS  Google Scholar 

  58. Eriksson, C., Bjorklund, A., & Wictorin, K. (2003). Neuronal differentiation following transplantation of expanded mouse neurosphere cultures derived from different embryonic forebrain regions. Experimental Neurology, 184(2), 615–635.

    Article  PubMed  Google Scholar 

  59. McBride, J. L., Behrstock, S. P., Chen, E. Y., et al. (2004). Human neural stem cell transplants improve motor function in a rat model of Huntington’s disease. The Journal of Comparative Neurology, 475(2), 211–219.

    Article  PubMed  Google Scholar 

  60. Visnyei, K., Tatsukawa, K. J., Erickson, R. I., et al. (2006). Neural progenitor implantation restores metabolic deficits in the brain following striatal quinolinic acid lesion. Experimental Neurology, 197(2), 465–474.

    Article  PubMed  Google Scholar 

  61. Fricker, R. A., Carpenter, M. K., Winkler, C., Greco, C., Gates, M. A., & Björklund, A. (1999). Site-specific migration and neuronal differentiation of human neural progenitor cells after transplantation in the adult rat brain. Journal of Neuroscience, 19(14), 5990–6005.

    PubMed  CAS  Google Scholar 

  62. Armstrong, R. J., Watts, C., Svendsen, C. N., Dunnett, S. B., & Rosser, A. E. (2000). Survival, neuronal differentiation, and fiber outgrowth of propagated human neural precursor grafts in an animal model of Huntington’s disease. Cell Transplantation, 9(1), 55–64.

    PubMed  CAS  Google Scholar 

  63. Zhang, R.L., Zhang, L., Zhang, Z.G., et al. (2003). Migration and differentiation of adult rat subventricular zone progenitor cells transplanted into the adult rat striatum. Nsci. 116(2):373–382.

    Google Scholar 

  64. Toresson, H., Mata, d.U., Fagerstrom, C., Perlmann, T., Campbell, K. (1999). Retinoids are produced by glia in the lateral ganglionic eminence and regulate striatal neuron differentiation. D. 126(6), 1317–1326.

  65. Fricker, R.A., Sirinathsinghji, D.J.S., Torres, E.M., Hume, S., Dunnett, S.B. (1997). The effects of donor stage on the survival and function of embryonic striatal grafts. I. Anatomy and development of the grafts. Nsci. 79, 695–710.

    Google Scholar 

  66. Fricker-Gates, R. A., Lundberg, C., & Dunnett, S. B. (2001). Neural transplantation: Restoring complex circuitry in the striatum. Restorative Neurology and Neuroscience, 19(1–2), 119–138.

    PubMed  CAS  Google Scholar 

  67. Chiba, S., Lee, Y.M., Zhou, W., Freed, C.R. (2008). Noggin enhances dopamine neuron production from human embryonic stem cells and improves behavioral outcome after transplantation into Parkinsonian rats. SC. 26(11), 2810–2820.

  68. Sonntag, K.C., Pruszak, J., Yoshizaki, T., van Arensbergen, J., Sanchez-Pernaute, R., Isacson, O. (2007). Enhanced yield of neuroepithelial precursors and midbrain-like dopaminergic neurons from human embryonic stem cells using the bone morphogenic protein antagonist noggin. SC. 25(2), 411–418.

  69. Morizane, A., Takahashi, J., Takagi, Y., Sasai, Y., & Hashimoto, N. (2002). Optimal conditions for in vivo induction of dopaminergic neurons from embryonic stem cells through stromal cell-derived inducing activity. Journal of Neuroscience Research, 69(6), 934–939.

    Article  PubMed  CAS  Google Scholar 

  70. Morizane, A., Takahashi, J., Shinoyama, M., et al. (2006). Generation of graftable dopaminergic neuron progenitors from mouse ES cells by a combination of coculture and neurosphere methods. Journal of Neuroscience Research, 83(6), 1015–1027.

    Article  PubMed  CAS  Google Scholar 

  71. Thinyane, K., Baier, P. C., Schindehutte, J., et al. (2005). Fate of pre-differentiated mouse embryonic stem cells transplanted in unilaterally 6-hydroxydopamine lesioned rats: Histological characterization of the grafted cells. Brain Research, 1045(1–2), 80–87.

    Article  PubMed  CAS  Google Scholar 

  72. Arnhold, S., Klein, H., Semkova, I., Addicks, K., & Schraermeyer, U. (2004). Neurally selected embryonic stem cells induce tumor formation after long-term survival following engraftment into the subretinal space. Investigative Ophthalmology & Visual Science, 45(12), 4251–4255.

    Article  Google Scholar 

  73. Bjorklund, L. M., Sanchez-Pernaute, R., Chung, S., et al. (2002). Embryonic stem cells develop into functional dopaminergic neurons after transplantation in a Parkinson rat model. Proceedings of the National Academy of Sciences of the United States of America, 99(4), 2344–2349.

    Article  PubMed  CAS  Google Scholar 

  74. Brederlau, A., Correia, A.S., Anisimov, S.V., et al. (2006). Transplantation of human embryonic stem cell-derived cells to a rat model of Parkinson’s disease: effect of in vitro differentiation on graft survival and teratoma formation. SC. 24(6), 1433–1440.

  75. Hedlund, E., Pruszak, J., Ferree, A., et al. (2007). Selection of embryonic stem cell-derived enhanced green fluorescent protein-positive dopamine neurons using the tyrosine hydroxylase promoter is confounded by reporter gene expression in immature cell populations. SC. 25(5), 1126–1135.

  76. Hedlund, E., Pruszak, J., Lardaro, T., et al. (2008). Embryonic stem cell-derived Pitx3-enhanced green fluorescent protein midbrain dopamine neurons survive enrichment by fluorescence-activated cell sorting and function in an animal model of Parkinson’s disease. SC. 26(6), 1526–1536.

  77. Friling, S., Andersson, E., Thompson, L. H., et al. (2009). Efficient production of mesencephalic dopamine neurons by Lmx1a expression in embryonic stem cells. Proceedings of the National Academy of Sciences of the United States of America, 106(18), 7613–7618.

    Article  PubMed  CAS  Google Scholar 

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Acknowledgements

We wish to thank Dr. Hugh Hemmings for the generous gift of the DARPP32 antibody. This research was supported by funding from Keele Medical School, Keele University, UK.

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Authors and Affiliations

  1. Institute for Science and Technology in Medicine, Keele University, Keele, ST5 5BG, UK

    Eunju Shin & Rosemary A. Fricker

  2. Neurosurgeon Group, Institute for Science and Technology in Medicine, Keele University, Keele, ST5 5BG, UK

    Mary J. Palmer

  3. MRC Clinical Sciences Centre, Experimental and Clinical Neuroscience Section, Faculty of Medicine, Imperial College London, Hammersmith Hospital Campus, Du Cane Road, London, W12 0NN, UK

    Meng Li

  4. Schools of Medicine and Life Sciences, & Institute for Science and Technology in Medicine, Keele University, Huxley Building, Keele, ST5 5BG, UK

    Rosemary A. Fricker

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  1. Eunju Shin
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Shin, E., Palmer, M.J., Li, M. et al. GABAergic Neurons from Mouse Embryonic Stem Cells Possess Functional Properties of Striatal Neurons In Vitro, and Develop into Striatal Neurons In Vivo in a Mouse Model of Huntington’s Disease. Stem Cell Rev and Rep 8, 513–531 (2012). https://doi.org/10.1007/s12015-011-9290-2

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