Toward stem cell-based phenotypic screens for neurodegenerative diseases

Nature Reviews Neurology

Volumn 11, Issue 6, 2015, Pages 339-350

  Khurana, Vikram ^a   Tardiff, Daniel F ^b   Chung, Chee Yeun ^b   Lindquist, Susan ^b  

^a HARVARD MEDICAL SCHOOL   (United States)

^b WHITEHEAD INSTITUTE FOR BIOMEDICAL RESEARCH   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ALPHA SYNUCLEIN;

CELL SURVIVAL; CELL TRANSDIFFERENTIATION; CELL VIABILITY; DEGENERATIVE DISEASE; GENE TARGETING; GENETIC DIFFERENCE; GENETIC RISK; HIGH THROUGHPUT SCREENING; HUMAN; NONHUMAN; NUCLEAR REPROGRAMMING; OXIDATIVE STRESS; PHENOTYPE; PLURIPOTENT STEM CELL; PRIORITY JOURNAL; PROTEIN EXPRESSION; REVIEW; SACCHAROMYCES CEREVISIAE; SIGNAL TRANSDUCTION; STEM CELL; YEAST CELL; BIOLOGICAL MODEL; GENETIC PREDISPOSITION; GENETIC SCREENING; GENETICS; GLIA; NERVE CELL; PROCEDURES;

GENETIC PREDISPOSITION TO DISEASE; GENETIC TESTING; HUMANS; MODELS, GENETIC; MODELS, NEUROLOGICAL; NEURODEGENERATIVE DISEASES; NEUROGLIA; NEURONS; SACCHAROMYCES CEREVISIAE; STEM CELLS;

EID: 84930574272     PISSN: 17594758     EISSN: 17594766     Source Type: Journal    
DOI: 10.1038/nrneurol.2015.79     Document Type: Review

References (86)

1. 10 facts on dementia. World Health Organization [online], http://www.who.int/features/factfiles/dementia/en/(2015).
2. Lowe, J., Mirra, S. S., Hyman, B. T. & Dickson, D. W. in Greenfield's Neuropathology 8th edn (eds Love, S. et al.) 1031-1152 (CRC Press, 2008).
3. Goedert, M., Spillantini, M. G., Del Tredici, K. & Braak, H. 100 years of Lewy pathology. Nat. Rev. Neurol. 9, 13-24 (2013).
4. Yamanaka, S. Induced pluripotent stem cells: past, present, and future. Cell Stem Cell 10, 678-684 (2012).
5. Yang, N. et al. Generation of oligodendroglial cells by direct lineage conversion. Nat. Biotechnol. 31, 434-439 (2013).
6. Vierbuchen, T. et al. Direct conversion of fibroblasts to functional neurons by defined factors. Nature 463, 1035-1041 (2010).
7. Swinney, D. C. & Anthony, J. How were new medicines discovered? Nat. Rev. Drug Discov. 10, 507-519 (2011).
8. Lee, B.-H., Finley, D. & King, R. W. A high-throughput screening method for identification of inhibitors of the deubiquitinating enzyme USP14. Curr. Protoc. Chem. Biol. 4, 311-330 (2012).
9. Lee, B.-H. et al. Enhancement of proteasome activity by a small-molecule inhibitor of USP14. Nature 467, 179-184 (2010).
10. Taipale, M. et al. Chaperones as thermodynamic sensors of drug-target interactions reveal kinase inhibitor specificities in living cells. Nat. Biotechnol. 31, 630-637 (2013).
11. Treusch, S. et al. Functional links between A? toxicity, endocytic trafficking, and Alzheimer's disease risk factors in yeast. Science 334, 1241-1245 (2011).
12. Volpicelli-Daley, L. A. et al. Exogenous ?-synuclein fibrils induce Lewy body pathology leading to synaptic dysfunction and neuron death. Neuron 72, 57-71 (2011).
13. Chung, C. Y. et al. Identification and rescue of ?-synuclein toxicity in Parkinson patient-derived neurons. Science 342, 983-987 (2013).
14. Khurana, V. & Lindquist, S. Modelling neurodegeneration in Saccharomyces cerevisiae: why cook with baker's yeast? Nat. Rev. Neurosci. 11, 436-449 (2010).
15. Lambert, J. C. et al. Meta-analysis of 74, 046 individuals identifies 11 new susceptibility loci for Alzheimer's disease. Nat. Genet. 45, 1452-1458 (2013).
16. Guerreiro, R., Brás, J. & Hardy, J. SnapShot: Genetics of ALS and FTD. Cell 160, 798-798e1 (2015).
17. Brás, J., Guerreiro, R. & Hardy, J. SnapShot: enetics of Parkinson's disease. Cell 160, 570-570e1 (2015).
18. Huang, Z. et al. A functional variomics tool for discovering drug-resistance genes and drug targets. Cell Rep. 3, 577-585 (2013).
19. Narayan, P., Ehsani, S. & Lindquist, S. Combating neurodegenerative disease with chemical probes and model systems. Nat. Chem. Biol. 10, 911-920 (2014).
20. Yeger-Lotem, E. et al. Bridging high-throughput genetic and transcriptional data reveals cellular responses to alpha-synuclein toxicity. Nat. Genet. 41, 316-323 (2009).
21. Cooper, A. A. et al. Synuclein blocks ER-Golgi traffic and Rab1 rescues neuron loss in Parkinson's models. Science 313, 324-328 (2006).
22. Gitler, A. D. et al.-Synuclein is part of a diverse and highly conserved interaction network that includes PARK9 and manganese toxicity. Nat. Genet. 41, 308-315 (2009).
23. Treusch, S., Cyr, D. M. & Lindquist, S. Amyloid deposits: protection against toxic protein species Cell Cycle 8, 1668-1674 (2009).
24. Gitler, A. D. et al. The Parkinson's disease protein-synuclein disrupts cellular Rab homeostasis. Proc. Natl Acad. Sci. USA 105, 145-150 (2008).
25. Soper, J. H., Kehm, V., Burd, C. G., Bankaitis, V. A. & Lee, V. M. Aggregation of-synuclein in S. cerevisiae is associated with defects in endosomal trafficking and phospholipid biosynthesis. J. Mol. Neurosci. 43, 391-405 (2011).
26. Thayanidhi, N. et al.-Synuclein delays endoplasmic reticulum (ER)-to-Golgi transport in mammalian cells by antagonizing ER/Golgi SNAREs. Mol. Biol. Cell 21, 1850-1863 (2010).
27. Mazzulli, J. R. et al. Gaucher disease glucocerebrosidase and-synuclein form a bidirectional pathogenic loop in synucleinopathies. Cell 146, 37-52 (2011).
28. Macleod, D. A. et al. RAB7L1 interacts with LRRK2 to modify intraneuronal protein sorting and Parkinson's disease risk. Neuron 77, 425-439 (2013).
29. Matlack, K. E. et al. Clioquinol promotes the degradation of metal-dependent amyloid-(A) oligomers to restore endocytosis and ameliorate A toxicity. Proc. Natl Acad. Sci. USA 111, 4013-4018 (2014).
30. Dhungel, N. et al. Parkinson's disease genes VPS35 and EIF4G1 interact genetically and converge on-synuclein. Neuron 85, 76-87 (2015).
31. Elden, A. C. et al. Ataxin-2 intermediate-length polyglutamine expansions are associated with increased risk for ALS. Nature 466, 1069-1075 (2010).
32. Chambers, S. M. et al. Highly efficient neural conversion of human ES and iPS cells by dual inhibition of SMAD signaling. Nat. Biotechnol. 27, 275-280 (2009).
33. Krencik, R., Weick, J. P., Liu, Y., Zhang, Z.-J. & Zhang, S.-C. Specification of transplantable astroglial subtypes from human pluripotent stem cells. Nat. Biotechnol. 29, 528-534 (2011).
34. 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).
35. Takahashi, K. et al. Induction of pluripotent stem cells from adult human fibroblasts by defined factors. Cell 131, 861-872 (2007).
36. 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).
37. Zhou, T. et al. Generation of human induced pluripotent stem cells from urine samples. Nat. Protoc. 7, 2080-2089 (2012).
38. Warren, L. et al. Highly efficient reprogramming to pluripotency and directed differentiation of human cells with synthetic modified mRNA. Cell Stem Cell 7, 618-630 (2010).
39. Yu, J. et al. Human induced pluripotent stem cells free of vector and transgene sequences. Science 324, 797-801 (2009).
40. Okita, K. et al. A more efficient method to generate integration-free human iPS cells. Nat. Methods 8, 409-412 (2011).
41. Zhang, Y. et al. Rapid single-step induction of functional neurons from human pluripotent stem cells. Neuron 78, 785-798 (2013).
42. Sandoe, J. & Eggan, K. Opportunities and challenges of pluripotent stem cell neurodegenerative disease models. Nat. Neurosci. 16, 780-789 (2013).
43. Ran, F. A. et al. Double nicking by RNA-guided CRISPR Cas9 for enhanced genome editing specificity. Cell 154, 1380-1389 (2013).
44. Hsu, P. D. et al. DNA targeting specificity of RNA-guided Cas9 nucleases. Nat. Biotechnol. 31, 827-832 (2013).
45. Wang, H. et al. One-step generation of mice carrying mutations in multiple genes by CRISPR/Cas-mediated genome engineering. Cell 153, 910-918 (2013).
46. Jack, C. R. Jr et al. Tracking pathophysiological processes in Alzheimer's disease: an updated hypothetical model of dynamic biomarkers. Lancet Neurol. 12, 207-216 (2013).
47. Shulman, J. M., De Jager, P. L. & Feany, M. B. Parkinson's disease: genetics and pathogenesis. Annu. Rev. Pathol. 6, 193-222 (2011).
48. Dickson, D. W. et al. Neuropathology of non-motor features of Parkinson disease. Parkinsonism Relat. Disord. 15 (Suppl. 3), S1-S5 (2009).
49. 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, 141ra90 (2012).
50. Nguyen, H. N. et al. LRRK2 mutant iPSC-derived DA neurons demonstrate increased susceptibility to oxidative stress. Cell Stem Cell 8, 267-280 (2011).
51. Ryan, S. D. et al. Isogenic human iPSC Parkinson's model shows nitrosative stress-induced dysfunction in MEF2-PGC1 transcription. Cell 155, 1351-1364 (2013).
52. Miller, J. D. et al. Human iPSC-based modeling of late-onset disease via progerin-induced aging. Cell Stem Cell 13, 691-705 (2013).
53. Lee, G. et al. Modelling pathogenesis and treatment of familial dysautonomia using patient-specific iPSCs. Nature 461, 402-406 (2009).
54. Lee, G. et al. Large-scale screening using familial dysautonomia induced pluripotent stem cells identifies compounds that rescue IKBKAP expression. Nat. Biotechnol. 30, 1244-1248 (2012).
55. Ku, S. et al. Friedreich's ataxia induced pluripotent stem cells model intergenerational GAATTC triplet repeat instability. Cell Stem Cell 7, 631-637 (2010).
56. Hick, A. et al. Neurons and cardiomyocytes derived from induced pluripotent stem cells as a model for mitochondrial defects in Friedreich's ataxia. Dis. Model. Mech. 6, 608-621 (2013).
57. Almeida, S. et al. Induced pluripotent stem cell models of progranulin-deficient frontotemporal dementia uncover specific reversible neuronal defects. Cell Rep. 2, 789-798 (2012).
58. Sanders, L. H. et al. LRRK2 mutations cause mitochondrial DNA damage in iPSC-derived neural cells from Parkinson's disease patients: reversal by gene correction. Neurobiol. Dis. 62, 381-386 (2014).
59. Ebert, A. D. et al. Induced pluripotent stem cells from a spinal muscular atrophy patient. Nature 457, 277-280 (2009).
60. Sendtner, M. Therapy development in spinal muscular atrophy. Nat. Neurosci. 13, 795-799 (2010).
61. Naryshkin, N. A. et al. Motor neuron disease. SMN2 splicing modifiers improve motor function and longevity in mice with spinal muscular atrophy. Science 345, 688-693 (2014).
62. Harper, S. Q. et al. RNA interference improves motor and neuropathological abnormalities in a Huntington's disease mouse model. Proc. Natl Acad. Sci. USA 102, 5820-5825 (2005).
63. Xia, H. et al. RNAi suppresses polyglutamine-induced neurodegeneration in a model of spinocerebellar ataxia. Nat. Med. 10, 816-820 (2004).
64. Keiser, M. S., Geoghegan, J. C., Boudreau, R. L., Lennox, K. A. & Davidson, B. L. RNAi or overexpression: alternative therapies for Spinocerebellar Ataxia Type 1. Neurobiol. Dis. 56, 6-13 (2013).
65. Sareen, D. et al. Targeting RNA foci in iPSC-derived motor neurons from ALS patients with a C9ORF72 repeat expansion. Sci. Transl. Med. 5, 208ra149 (2013).
66. Xu, X. et al. Prevention of-amyloid induced toxicity in human iPS cell-derived neurons by inhibition of Cyclin-dependent kinases and associated cell cycle events. Stem Cell Res. 10, 213-227 (2013).
67. Yahata, N. et al. Anti-A drug screening platform using human iPS cell-derived neurons for the treatment of Alzheimer's disease. PLoS ONE 6, e25788 (2011).
68. Kondo, T. et al. Modeling Alzheimer's disease with iPSCs reveals stress phenotypes associated with Intracellular A and differential drug responsiveness. Cell Stem Cell 12, 487-496 (2013).
69. Burkhardt, M. F. et al. A cellular model for sporadic ALS using patient-derived induced pluripotent stem cells. Mol. Cell. Neurosci. 56, 355-364 (2013).
70. Barmada, S. J. et al. Autophagy induction enhances TDP43 turnover and survival in neuronal ALS models. Nat. Chem. Biol. 10, 677-685 (2014).
71. Skibinski, G. & Finkbeiner, S. Drug discovery in Parkinson's disease-update and developments in the use of cellular models. Int. J. High Throughput Screen. 2011, 15-25 (2011).
72. Egawa, N. et al. Drug screening for ALS using patient-specific induced pluripotent stem cells. Sci. Transl. Med. 4, 145ra104 (2012).
73. Yang, Y. M. et al. A small molecule screen in stem-cell-derived motor neurons identifies a kinase inhibitor as a candidate therapeutic for ALS. Cell Stem Cell 12, 713-726 (2013).
74. Hoïng, S. et al. Discovery of inhibitors of microglial neurotoxicity acting through multiple mechanisms using a stem-cell-based phenotypic assay. Cell Stem Cell 11, 620-632 (2012).
75. Tardiff, D. F., Khurana, V., Chung, C. Y. & Lindquist, S. From yeast to patient neurons and back again: powerful new discovery platforms. Mov. Disord. 10, 1231-1240 (2014).
76. Tardiff, D. F. et al. Yeast reveal a "druggable" Rsp5/Nedd4 network that ameliorates-synuclein toxicity in neurons. Science 342, 979-983 (2013).
77. Auluck, P. K., Caraveo, G. & Lindquist, S.-Synuclein: membrane interactions and toxicity in Parkinson's disease. Annu. Rev. Cell Dev. Biol. 26, 211-233 (2010).
78. Hu, G. & Luo, J. A primer on using pooled shRNA libraries for functional genomic screens. Acta Biochim. Biophys. Sin. (Shanghai) 44, 103-112 (2012).
79. Hasson, S. A. et al. High-content genome-wide RNAi screens identify regulators of parkin upstream of mitophagy. Nature 504, 291-295 (2013).
80. Seibler, P. et al. Mitochondrial Parkin recruitment is impaired in neurons derived from mutant PINK1 induced pluripotent stem cells. J. Neurosci. 31, 5970-5976 (2011).
81. Shalem, O. et al. Genome-scale CRISPR-Cas9 knockout screening in human cells. Science 343, 84-87 (2014).
82. Wang, T., Wei, J. J., Sabatini, D. M. & Lander, E. S. Genetic screens in human cells using the CRISPR-Cas9 system. Science 343, 80-84 (2014).
83. Leeb, M. & Wutz, A. Derivation of haploid embryonic stem cells from mouse embryos. Nature 479, 131-134 (2011).
84. Elling, U. et al. Forward and reverse genetics through derivation of haploid mouse embryonic stem cells. Cell Stem Cell 9, 563-574 (2011).
85. Son, E. Y. et al. Conversion of mouse and human fibroblasts into functional spinal motor neurons. Cell Stem Cell 9, 205-218 (2011).
86. Gupta, R. M. & Musunuru, K. Expanding the genetic editing tool kit: ZFNs, TALENs, and CRISPR-Cas9. J. Clin. Invest. 124, 4154-4161 (2014).