Using human neural stem cells to model neurological disease

Nature Reviews Genetics

Volumn 5, Issue 2, 2004, Pages 136-144

  Jakel, Rebekah J ^a,b   Schneider, Bernard L ^b   Svendsen, Clive N ^a,b  

^a UNIVERSITY OF WISCONSIN SCHOOL OF MEDICINE AND PUBLIC HEALTH   (United States)

^b UNIVERSITY OF WISCONSIN MADISON   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

DNA; DOUBLE STRANDED RNA; GREEN FLUORESCENT PROTEIN; MESSENGER RNA; N METHYL DEXTRO ASPARTIC ACID RECEPTOR; SYNUCLEIN; VIRUS VECTOR;

ADULT; AMYOTROPHIC LATERAL SCLEROSIS; ANIMAL MODEL; ASTROCYTE; BASAL GANGLION; BRAIN; DOPAMINERGIC NERVE CELL; EMBRYO; ETHICS; FETUS; GENE EXPRESSION; GENE MUTATION; GENETIC RECOMBINATION; HIPPOCAMPUS; HUMAN; HUMAN CELL; HUNTINGTON CHOREA; LEWY BODY; MODEL; MOUSE; NERVE CELL; NEURAL STEM CELL; NEUROLOGIC DISEASE; NONHUMAN; OLIGODENDROGLIA; PARKINSON DISEASE; POINT MUTATION; POLITICS; POLYMERASE CHAIN REACTION; PRIORITY JOURNAL; REVIEW; STEM CELL; SUBSTANTIA NIGRA; TRANSGENIC MOUSE;

EMBRYO; FETUS; HUMANS; MODELS, BIOLOGICAL; MUTATION; NERVE TISSUE PROTEINS; NERVOUS SYSTEM DISEASES; NEURODEGENERATIVE DISEASES; NEURONS; STEM CELLS;

ANIMALIA; MUS MUSCULUS; RODENTIA;

EID: 0742305862     PISSN: 14710056     EISSN: None     Source Type: Journal    
DOI: 10.1038/nrg1268     Document Type: Review

References (106)

1. Klivenyi, P. et al. Neuroprotective effects of creatine in a transgenic animal model of amyotrophic lateral sclerosis. Nature Med. 5, 347-350 (1999).
2. Groeneveld, G. J. et al. A randomized sequential trial of creatine in amyotrophic lateral sclerosis. Ann. Neurol. 53, 437-445 (2003).
3. Gasser, T. et al. A susceptibility locus for Parkinson's disease maps to chromosome 2p13. Nature Genet. 18, 262-265 (1998).
4. Bonifati, V. et al. Mutations in the DJ-1 gene associated with autosomal recessive early-onset parkinsonism. Science 299, 256-259 (2003).
5. Taylor, J. P., Hardy, J. & Fischbeck, K. H. Toxic proteins in neurodegenerative disease. Science 296, 1991-1995 (2002).
6. Reaume, A. G. et al. Motor neurons in Cu/Zn superoxide dismutase-deficient mice develop normally but exhibit enhanced cell death after axonal injury. Nature Genet. 13, 43-47 (1996).
7. Gurney, M. E. et al. Motor neuron degeneration in mice that express a human Cu,Zn superoxide dismutase mutation. Science 264, 1772-1775 (1994).
8. Zhang, B., Tu, P., Abtahian, F., Trojanowski, J. Q. & Lee, V. M. Neurofilaments and orthograde transport are reduced in ventral root axons of transgenic mice that express human SOD1 with a G93A mutation. J. Cell Biol. 139, 1307-1315 (1997).
9. Howland, D. S. et al. Focal loss of the glutamate transporter EAAT2 in a transgenic rat model of SOD1 mutant-mediated amyotrophic lateral sclerosis (ALS). Proc. Natl Acad. Sci. USA 99, 1604-1609 (2002). Shows that mutant SOD1 can be transgenically expressed in rats, leading to motoneuron death and changes in glial function. However, to obtain a phenotype similar to that of humans requires the insertion of multiple copies of the mutant gene; this is unlike the human disease in which one copy of mutant SOD1 is sufficient to cause ALS.
10. Betarbet, R., Sherer, T. B. & Greenamyre, J. T. Animal models of Parkinson's disease. Bioessays 24, 308-318 (2002).
11. Beal, M. F. Experimental models of Parkinson's disease. Nature Rev. Neurosci. 2, 325-334 (2001).
12. Corsini, G. U., Pintus, S., Bocchetta, A., Piccardi, M. P. & Del Zompo, M. Primate-rodent 3H-MPTP binding differences, and biotransformation of MPTP to a reactive intermediate in vitro. J. Neural Transm. Suppl. 22, 55-60 (1986).
13. Kitada, T. et al. Mutations in the parkin gene cause autosomal recessive juvenile parkinsonism. Nature 392, 605-608 (1998).
14. Polymeropoulos, M. H. et al. Mutation in the α-synuclein gene identified in families with Parkinson's disease. Science 276, 2045-2047 (1997).
15. Kruger, R. et al. Ala30Pro mutation in the gene encoding α-synuclein in Parkinson's disease. Nature Genet. 18, 106-108 (1998).
16. Feany, M. B. & Bender, W. W. A Drosophila model of Parkinson's disease. Nature 404, 394-398 (2000). First fly model of a human neurodegenerative disease. Dopamine neurons were selectively lost and the files had motor deficits.
17. van der, P. H. et al. Neuropathology in mice expressing human α-synuclein. J. Neurosci. 20, 6021-6029 (2000).
18. Masliah, E. et al. Dopaminergic loss and inclusion body formation in α-synuclein mice: implications for neurodegenerative disorders. Science 287, 1265-1269 (2000).
19. Lee, M. K. et al. Human α-synuclein-harbodng familial Parkinson's disease-linked Ala-53 → Thr mutation causes neurodegenerative disease with α-synuclein aggregation in transgenic mice. Proc. Natl Acad. Sci. USA 99, 8968-8973 (2002).
20. Giasson, B. I. et al. Neuronal α-synucleinopathy with severe movement disorder in mice expressing A53T human α-synuclein. Neuron 34, 521-533 (2002).
21. Rathke-Hartlieb, S. et al. Sensitivity to MPTP is not increased in Parkinson's disease-associated mutant α-synuclein transgenic mice. J. Neurochem. 77, 1181-1184 (2001).
22. Lo Bianco, C., Ridet, J. L., Schneider, B. L., Deglon, N. & Aebischer, P. α-synucleinopathy and selective dopaminergic neuron loss in a rat lentiviral-based model of Parkinson's disease. Proc. Natl Acad. Sci. USA 99, 10813-10818 (2002).
23. Kirik, D. et al. Parkinson-like neurodegeneration induced by targeted overexpression of α-synuclein in the nigrostriatal system. J. Neurosci. 22, 2780-2791 (2002).
24. Kirik, D. et al. Nigrostriatal α-synucleinopathy induced by viral vector-mediated overexpression of human α-synuclein: a new primate model of Parkinson's disease. Proc. Natl Acad. Sci. USA 100, 2884-2889 (2003).
25. Singleton, A. B. et al. α-synuclein locus triplication causes Parkinson's disease. Science 302, 841 (2003).
26. Outeiro, T. F. & Lindquist, S. Yeast cells provide insight into α-synuclein biology and pathobiology. Science 302, 1772-1775 (2003).
27. Willingham, S., Outeiro, T. F., DeVit, M. J., Lindquist, S. L. & Muchowski, P. J. Yeast genes that enhance the toxicity of a mutant huntingtin fragment or {α}-synuclein. Science 302, 1769-1772 (2003). First paper to use yeast cells to model differences in molecular and cellular changes associated with either huntingtin or synuclein.
28. The Huntington's Disease Collaborative Research Group. A novel gene containing a trinucleotide repeat that is expanded and unstable on Huntington's disease chromosomes. Cell 72, 971-983 (1993).
29. Mangiarini, L. et al. Exon 1 of the HD gene with an expanded CAG repeat is sufficient to cause a progressive neurological phenotype in transgenic mice. Cell 87, 493-506 (1996).
30. Hodgson, J. G. et al. A YAC mouse model for Huntington's disease with full-length mutant huntingtin, cytoplasmic toxicity, and selective striatal neurodegeneration. Neuron 23, 181-192 (1999).
31. Martindale, D. et al. Length of huntingtin and its polyglutamine tract influences localization and frequency of intracellular aggregates. Nature Genet. 18, 150-154 (1998).
32. Li, S. H., Cheng, A. L., Li, H. & Li, X. J. Cellular defects and altered gene expression in PC12 cells stably expressing mutant huntingtin. J. Neurosci. 19, 5159-5172 (1999).
33. Peters, M. F. et al. Nuclear targeting of mutant Huntingtin increases toxicity. Mol. Cell Neurosci. 14, 121-128 (1999).
34. Wheeler, V. C. et al. Length-dependent gametic CAG repeat instability in the Huntington's disease knock-in mouse. Hum. Mol. Genet. 8, 115-122 (1999).
35. Morton, A. J. & Leavens, W. Mice transgenic for the human Huntington's disease mutation have reduced sensitivity to kainic acid toxicity. Brain Res. Bull. 52, 51-59 (2000).
36. Petersen, A. et al. Mice transgenic for exon 1 of the Huntington's disease gene display reduced striatal sensitivity to neurotoxicity induced by dopamine and 6-hydroxydopamine. Eur. J. Neurosci. 14, 1425-1435 (2001).
37. Petersen, A. et al. Maintenance of susceptibility to neurodegeneration following intrastriatal injections of quinolinic acid in a new transgenic mouse model of Huntington's disease. Exp. Neurol. 175, 297-300 (2002).
38. Snider, B. J. et al. Neocortical neurons cultured from mice with expanded CAG repeats in the huntingtin gene: unaltered vulnerability to excitotoxins and other insults. Neuroscience 120, 617-625 (2003).
39. Wang, X. et al. Immunochemical evidence that human apoB differs when expressed in rodent versus human cells. J. Lipid Res. 44, 547-553 (2003).
40. Ishii, S. et al. α-galactosidase transgenic mouse: heterogeneous gene expression and posttranslational glycosylation in tissues. Glycoconj. J. 15, 591-594 (1998).
41. Kempermann, G., Kuhn, H. G. & Gage, F. H. Genetic influence on neurogenesis in the dentate gyrus of adult mice. Proc. Natl Acad. Sci. USA 94, 10409-10414 (1997).
42. Carlson, G. A. et al. Genetic modification of the phenotypes produced by amyloid precursor protein overexpression in transgenic mice. Hum. Mol. Genet. 6, 1951-1959 (1997).
43. Elsea, S. H. & Lucas, R. E. The mousetrap: what we can learn when the mouse model does not mimic the human disease. ILAR J. 43, 66-79 (2002).
44. Wright, W. E. & Shay, J. W. Telomere dynamics in cancer progression and prevention: fundamental differences in human and mouse telomere biology. Nature Med. 6, 849-851 (2000).
45. Yoshimi, N. et al. Telomerase activity of normal tissues and neoplasms in rat colon carcinogenesis induced by methylazoxymethanol acetate and its difference from that of human colonic tissues. Mol. Carcinog. 16, 1-5 (1996).
46. Ostenfeld, T. et al. Human neural precursor cells express low levels of telomerase in vitro and show diminishing cell proliferation with extensive axonal outgrowth following transplantation. Exp. Neurol. 164, 215-226 (2000).
47. Strong, T. V. et al. Widespread expression of the human and rat Huntington's disease gene in brain and nonneural tissues. Nature Genet. 5, 259-265 (1993).
48. Sawa, A. et al. Increased apoptosis of Huntington disease lymphoblasts associated with repeat length-dependent mitochondrial depolarization. Nature Med. 5, 1194-1198 (1999).
49. Jakab, K. et al. UVB irradiation-induced apoptosis increased in lymphocytes of Huntington's disease patients. Neuroreport 12, 1653-1656 (2001).
50. Tonini, G. P. Neoroblastoma: the result of multistep transformation? Stem Cells 11, 276-282 (1993).
51. Tweddle, D. A. et al. The p53 pathway and its inactivation in neuroblastoma. Cancer Lett. 197, 93-98 (2003).
52. Goggi, J. et al. The neuronal survival effects of rasagiline and deprenyl on fetal human and rat ventral mesencephalic neurons in culture. Neuroreport 11, 3937-3941 (2000).
53. Zhou, W., Schaack, J., Zawada, W. M. & Freed, C. R. Overexpression of human [α]-synuclein causes dopamine neuron death in primary human mesencephalic culture. Brain Res. 926, 42-50 (2002).
54. Xu, J. et al. Dopamine-dependent neurotoxicity of α-synuclein: a mechanism for selective neurodegeneration in Parkinson disease. Nature Med. 8, 600-606 (2002).
55. Thomson, J. A. et al. Embryonic stem cell lines derived from human blastocyts. Science 282, 1145-1147 (1998).
56. 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. Nature Biotechnol. 19, 1129-1133 (2001).
57. Reubinoff, B. E. et al. Neural progenitors from human embryonic stem cells. Nature Biotechnol. 19, 1134-1140 (2001). Together with REF. 56, this paper describes how neural cells can be derived from human ES cells in culture.
58. Svendsen, C. N. et al. A new method for the rapid and long term growth of human neural precursor cells. J. Neurosci. Methods 85, 141-153 (1998).
59. Carpenter, M. K. et al. In vitro expansion of a multipotent population of human neural progenitor cells. Exp. Neurol. 156, 265-278 (1999).
60. Vescovi, A. L. et al. Isolation and cloning of multipotential stem cells from the embryonic human CNS and establishment of transplantable human neural stem cell lines by epigenetic stimulation. Exp. Neurol. 156, 71-83 (1999).
61. Sabate, O. et al. Transplantation to the rat brain of human neural progenitors that were genetically modified using adenoviruses. Nature Genet. 9, 256-260 (1995).
62. Reynolds, B. A. & Weiss, S. Generation of neurons and astrocytes from isolated cells of the adult mammalian central nervous system. Science 255, 1707-1710 (1992).
63. Wright, L. S. et al. Gene expression in human neural stem cells: effects of leukemia inhibitory factor. J. Neurochem. 86, 179-195 (2003). Demonstrates the reproducibility and reliability of microarray analysis of human neural stem-cell cultures and their maintainance over time.
64. Johansson, C. B. et al. Identification of a neural stem cell in the adult mammalian central nervous system. Cell 96, 25-34 (1999).
65. Palmer, T. D., Ray, J. & Gage, F. H. FGF-2-responsive neuronal progenitors reside in proliferative and quiescent regions of the adult rodent brain. Mol. Cell Neurosci. 6, 474-486 (1995).
66. Palmer, T. D., Takahashi, J. & Gage, F. H. The adult rat hippocampus contains primordial neural stem cells. Mol. Cell Neurosci 8, 389-404 (1997).
67. Pincus, D. W. et al. Fibroblast growth factor-2/brain-derived neurotrophic factor-associated maturation of new neurons generated from adult human subependymal cells. Ann. Neurol. 43, 576-585 (1998).
68. Roy, N. S. et al. In vitro neurogenesis by progenitor cells isolated from the adult human hippocampus. Nature Med. 6, 271-277 (2000).
69. Nunes, M. C. et al. Identification and isolation of multipotential neural progenitor cells from the subcortical white matter of the adult human brain. Nature Med. 9, 439-447 (2003).
70. Johansson, C. B., Svensson, M., Wallstedt, L., Janson, A. M. & Frisen, J. Neural stem cells in the adult human brain. Exp. Cell Res. 253, 733-736 (1999).
71. Ostenfeld, T. et al. Regional specification of rodent and human neurospheres. Brain Res. Dev. Brain Res. 134, 43-55 (2002).
72. Hitoshi, S., Tropepe, V., Ekker, M. & van der, K. D. Neural stem cell lineages are regionally specified, but not committed, within distinct compartments of the developing brain. Development 129, 233-244 (2002).
73. D'Amour, K. A. & Gage, F. H. Genetic and functional differences between multipotent neural and pluripotent embryonic stem cells. Proc. Natl Acad. Sci. USA 100, 11866-11872 (2003).
74. Bhattacharyya, A. & Svendsen, C. N. Human neural stem cells: a new tool for studying cortical development in Down's syndrome. Genes Brain Behav. 2, 179-186 (2003).
75. Qian, X. et al. Timing of CNS cell generation: a programmed sequence of neuron and glial cell production from isolated murine cortical stem cells. Neuron 28, 69-80 (2000).
76. Pfeifer, A. Ikawa, M., Dayn, Y. & Verma, I. M. Transgenesis by lentiviral vectors: lack of gene silencing in mammalian embryonic stem cells and preemplantation embryos. Proc. Natl Acad. Sci. USA 99, 2140-2145 (2002).
77. Wu, P., Ye, Y. & Svendsen, C. N. Transduction of human neural progenitor cells using recombinant adeno-associated viral vectors. Gene Ther. 9, 245-255 (2002).
78. Ostenfeld, T. et al. Neurospheres modified to produce glial cell line-derived neurotrophic factor increase the survival of transplanted dopamine neurons. J. Neurosci. Res. 69, 955-965 (2002).
79. Kafri, T., van Praag, H., Gage, F. H. & Verma, I. M. Lentiviral vectors: regulated gene expression. Mol. Ther. 1, 516-521 (2000).
80. Belteki, G., Gertsenstein, M., Ow, D. W. & Nagy, A. Site-specific cassette exchange and germline transmission with mouse ES cells expressing phiC31 integrase. Nature Biotechnol. 21, 321-324 (2003). Shows the use of a Streptomyces phage integrase to obtain site-specific transgene integration in mouse ES cells.
81. Zwaka, T. P. & Thomson, J. A. Homologous recombination in human embryonic stem cells. Nature Biotechnol. 21, 319-321 (2003). Reports the first example of gene insertion through homologous recombination in human embryonic stem cells.
82. Abe, Y. et al. Analysis of neurons created from wild-type and Alzheimer's mutation knock-in embryonic stem cells by a highly efficient differentiation protocol. J. Neurosci. 23, 8513-8525 (2003). One of the first examples to show the utility of stem cells to examine the neuropathology of familial Alzheimer disease using homologous recombination.
83. Bahn, S. et al. Neuronal target genes of the neuron-restrictive silencer factor in neurospheres derived from fetuses with Down's syndrome: a gene expression study. Lancet 359, 310-315 (2002). Shows that neural stem calls can be derived and successfully cultured from human tissue that carries a mutation that is inherited naturally through the germline. Furthermore, gene-expression analysis showed previously unknown changes in the expression of genes that are crucial for cortical development.
84. Hoogeveen, A. T., Willemsen, R. & Oostra, B. A. Fragile X syndrome, the Fragile X related proteins, and animal models. Microsc. Res. Tech. 57, 148-155 (2002).
85. Wichterle, H., Lieberam, I., Porter, J. A. & Jessell, T. M. Directed differentiation of embryonic stem cells into motor neurons. Cell 110, 385-397 (2002).
86. Silani, V., Braga, M., Ciammola, A., Cardin, V. & Scarlato, G. Motor neurons in culture as a model to study ALS. J. Neurol. 247 (Suppl 1), 128-136 (2000).
87. Silani, V. et al. Human developing motor neurons as a tool to study ALS. Amyotroph. Lateral. Scler. Other Motor Neuron Disord 2 (Suppl 1), S69-S76 (2001).
88. Rao, S. D., Yin, H. Z. & Weiss, J. H. Disruption of glial glutamate transport by reactive oxygen species produced in motor neurons. J. Neurosci. 23, 2627-2633 (2003).
89. Caldwell, M. A. et al. Growth factors regulate the survival and fate of cells derived from human neurospheres. Nature Biotechnol. 19, 475-479 (2001).
90. Lotharius, J. & Brundin, P. Impaired dopamine storage resulting from α-synuclein mutations may contribute to the pathogenesis of Pakinson's disease. Hum. Mol. Genet. 11, 2395-2407 (2002).
91. Chu-LaGraff, Q., Kang, X. & Messer, A. Expression of the Huntington's disease transgene in neural stem cell cultures from R6/2 transgenic mice. Brain Res. Bull. 56, 307-312 (2001).
92. Bhide, P. G. et al. Expression of normal and mutant huntingtin in the developing brain. J. Neurosci. 16, 5523-5535 (1996).
93. Rasmussen, A. et al. Huntington disease in children: genotype-phenotype correlation. Neuropediatrics 31, 190-194 (2000).
94. Ramalho-Santos, M., Yoon, S., Matsuzaki, Y., Mulligan, R. C. & Melton, D. A. 'Stemness': transcriptional profiling of embryonic and adult stem cells. Science 298, 597-600 (2002).
95. Ivanova, N. B. et al. A stem cell molecular signature. Science 298, 601-604 (2002). Together with REF. 94, this paper has fuelled a discussion about how to detect basal gene expression that is specific to stem-cell populations (see REFS 95-99). The discussion has shown the complexity of ascertaining global gene expression in cell populations.
96. Evsikov, A. V. & Solter, D. Comment on "Stemness': transcriptional profiling of embryonic and adult stem cells' and 'a stem cell molecular signature'. Science 302, 393 (2003).
97. Fortunel, N. O. et al. Comment on "Stemness': transcriptional profiling of embryonic and adult stem cells' and 'a stem cell molecular signature'. Science 302, 393 (2003).
98. Vogel, G. Stem cells. 'Stemness' genes still elusive. Science 302, 371 (2003).
99. Geschwind, D. H. et al. A genetic analysis of neural progenitor differentiation. Neuron 29, 325-339 (2001).
100. Suslov, O. N., Kukekov, V. G., Ignatova, T. N. & Steindler, D. A. Neural stem cell heterogeneity demonstrated by molecular phenotyping of clonal neurospheres. Proc. Natl Acad. Sci. USA 99, 14506-14511 (2002).
101. Svendsen, C. N. & Caldwell, M. A. Neural stem cells in the developing central nervous system: implications for cell therapy through transplantation. Prog. Brain Res. 127, 13-34 (2000).
102. Richards, S.-J. et al. Transplants of mouse trisomy 16 hippocampus provide a model of Alzheimer's disease neuropathology. EMBO J. 10, 297-303 (1991).
103. Fletcher, L. US stem cell policy comes under fire. Nature Biotechnol. 19, 893-894 (2001).
104. Rowley, J. D., Blackburn, E., Gazzaniga, M. S. & Foster, D. W. Harmful moratorium on stem cell research. Science 297, 1957 (2002).
105. Kennedy, D. Stem cells: still here, still waiting. Science 300, 865 (2003).
106. Disease insights from stem cells. Nature 422, 787 (2003).