Polyglutamine (polyQ) disorders: The chromatin connection

Nucleus (United States)

Volumn 3, Issue 5, 2012, Pages

  Cohen Carmon, Dorit ^a   Meshorer, Eran ^a  

^a HEBREW UNIVERSITY OF JERUSALEM   (Israel)

Author keywords

Chromatin; Disease; HDAC inhibitors; IPS cells; Neurodegeneration; Pluripotent stem cells; Polyglutamine (polyQ)

Indexed keywords

BUTYRIC ACID; HISTONE DEACETYLASE INHIBITOR; POLYGLUTAMINE; VORINOSTAT;

CELL DIFFERENTIATION; CHROMATIN STRUCTURE; DEGENERATIVE DISEASE; ENZYME REGULATION; EPIGENETICS; GENETIC DISORDER; GENETIC REGULATION; GENOMIC INSTABILITY; HISTONE MODIFICATION; HUMAN; NONHUMAN; PATHOPHYSIOLOGY; PLURIPOTENT STEM CELL; POLYGLUTAMINE DISORDER; REVIEW; TRANSCRIPTION REGULATION; TRINUCLEOTIDE REPEAT;

EID: 84866139184     PISSN: 19491034     EISSN: 19491042     Source Type: Journal    
DOI: None     Document Type: Review

References (96)

1. Orr HT, Zoghbi HY. Trinucleotide repeat disorders. Annu Rev Neurosci 2007; 30:575-621; PMID:17417937; http://dx.doi.org/10.1146/annurev. neuro.29.051605.113042.
2. Liu Y, Wilson SH. DNA base excision repair: a mechanism of trinucleotide repeat expansion. Trends Biochem Sci 2012; 37:162-72; PMID:22285516; http://dx.doi.org/10.1016/j.tibs.2011.12.002.
3. Dion V, Wilson JH. Instability and chromatin structure of expanded trinucleotide repeats. Trends Genet 2009; 25:288-97; PMID:19540013; http://dx.doi. org/10.1016/j.tig.2009.04.007.
4. Grewal SI, Elgin SC. Transcription and RNA interference in the formation of heterochromatin. Nature 2007; 447:399-406; PMID:17522672; http://dx.doi. org/10.1038/nature05914.
5. Morris KV, Chan SW, Jacobsen SE, Looney DJ. Small interfering RNA-induced transcriptional gene silencing in human cells. Science 2004; 305:1289-92; PMID:15297624; http://dx.doi.org/10.1126/science. 1101372.
6. Kim DH, Villeneuve LM, Morris KV, Rossi JJ. Argonaute-1 directs siRNA-mediated transcriptional gene silencing in human cells. Nat Struct Mol Biol 2006; 13:793-7; PMID:16936726; http://dx.doi. org/10.1038/nsmb1142.
7. Lin Y, Leng M, Wan M, Wilson JH. Convergent transcription through a long CAG tract destabilizes repeats and induces apoptosis. Mol Cell Biol 2010; 30:4435-51; PMID:20647539; http://dx.doi.org/10.1128/MCB.00332-10.
8. Lawlor KT, O'Keefe LV, Samaraweera SE, van Eyk CL, McLeod CJ, Maloney CA, et al. Double-stranded RNA is pathogenic in Drosophila models of expanded repeat neurodegenerative diseases. Hum Mol Genet 2011; 20:3757-68; PMID:21724553; http://dx.doi. org/10.1093/hmg/ddr292.
9. Libby RT, Hagerman KA, Pineda VV, Lau R, Cho DH, Baccam SL, et al. CTCF cis-regulates trinucleotide repeat instability in an epigenetic manner: a novel basis for mutational hot spot determination. PLoS Genet 2008; 4:e1000257; PMID:19008940; http://dx.doi. org/10.1371/journal.pgen.1000257.
10. Dion V, Lin Y, Hubert L Jr., Waterland RA, Wilson JH. Dnmt1 deficiency promotes CAG repeat expansion in the mouse germline. Hum Mol Genet 2008; 17:1306-17; PMID:18252747; http://dx.doi.org/10.1093/hmg/ddn019.
11. Bodai L, Pallos J, Thompson LM, Marsh JL. Altered protein acetylation in polyglutamine diseases. Curr Med Chem 2003; 10:2577-87; PMID:14529472; http://dx.doi.org/10.2174/0929867033456530.
12. Jung J, Bonini N. CREB-binding protein modulates repeat instability in a Drosophila model for polyQ disease. Science 2007; 315:1857-9; PMID:17332375; http://dx.doi.org/10.1126/science.1139517.
13. Debacker K, Frizzell A, Gleeson O, Kirkham-McCarthy L, Mertz T, Lahue RS. Histone deacetylase complexes promote trinucleotide repeat expansions. PLoS Biol 2012; 10:e1001257; PMID:22363205; http://dx.doi. org/10.1371/journal.pbio.1001257.
14. Nightingale KP, O'Neill LP, Turner BM. Histone modifications: signalling receptors and potential elements of a heritable epigenetic code. Curr Opin Genet Dev 2006; 16:125-36; PMID:16503131; http://dx.doi. org/10.1016/j.gde.2006.02.015.
15. Benn CL, Sun T, Sadri-Vakili G, McFarland KN, DiRocco DP, Yohrling GJ, et al. Huntingtin modulates transcription, occupies gene promoters in vivo, and binds directly to DNA in a polyglutaminedependent manner. J Neurosci 2008; 28:10720-33; PMID:18923047; http://dx.doi.org/10.1523/JNEUROSCI.2126-08.2008.
16. Harjes P, Wanker EE. The hunt for huntingtin function: interaction partners tell many different stories. Trends Biochem Sci 2003; 28:425-33; PMID:12932731; http://dx.doi.org/10.1016/S0968-0004(03)00168-3.
17. Li SH, Li XJ. Huntingtin-protein interactions and the pathogenesis of Huntington's disease. Trends Genet 2004; 20:146-54; PMID:15036808; http://dx.doi. org/10.1016/j.tig.2004.01.008.
18. Luthi-Carter R, Hanson SA, Strand AD, Bergstrom DA, Chun W, Peters NL, et al. Dysregulation of gene expression in the R6/2 model of polyglutamine disease: parallel changes in muscle and brain. Hum Mol Genet 2002; 11:1911-26; PMID:12165554; http://dx.doi. org/10.1093/hmg/11.17.1911.
19. Stack EC, Kubilus JK, Smith K, Cormier K, Del Signore SJ, Guelin E, et al. Chronology of behavioral symptoms and neuropathological sequela in R6/2 Huntington's disease transgenic mice. J Comp Neurol 2005; 490:354-70; PMID:16127709; http://dx.doi. org/10.1002/cne.20680.
20. Mangiarini L, Sathasivam K, Seller M, Cozens B, Harper A, Hetherington C, 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 1996; 87:493-506; PMID:8898202; http://dx.doi.org/10.1016/S0092-8674(00)81369-0.
21. Schilling G, Becher MW, Sharp AH, Jinnah HA, Duan K, Kotzuk JA, et al. Intranuclear inclusions and neuritic aggregates in transgenic mice expressing a mutant N-terminal fragment of huntingtin. Hum Mol Genet 1999; 8:397-407; PMID:9949199; http://dx.doi.org/10.1093/hmg/8.3.397.
22. Ferrante RJ, Kubilus JK, Lee J, Ryu H, Beesen A, Zucker B, et al. Histone deacetylase inhibition by sodium butyrate chemotherapy ameliorates the neurodegenerative phenotype in Huntington's disease mice. J Neurosci 2003; 23:9418-27; PMID:14561870.
23. Jiang H, Poirier MA, Liang Y, Pei Z, Weiskittel CE, Smith WW, et al. Depletion of CBP is directly linked with cellular toxicity caused by mutant huntingtin. Neurobiol Dis 2006; 23:543-51; PMID:16766198; http://dx.doi.org/10.1016/j.nbd.2006.04.011.
24. Sadri-Vakili G, Bouzou B, Benn CL, Kim MO, Chawla P, Overland RP, et al. Histones associated with downregulated genes are hypo-acetylated in Huntington's disease models. Hum Mol Genet 2007; 16:1293-306; PMID:17409194; http://dx.doi.org/10.1093/hmg/ddm078.
25. Lee J, Hagerty S, Cormier KA, Kim J, Kung AL, Ferrante RJ, et al. Monoallele deletion of CBP leads to pericentromeric heterochromatin condensation through ESET expression and histone H3 (K9) methylation. Hum Mol Genet 2008; 17:1774-82; PMID:18319327; http://dx.doi.org/10.1093/hmg/ddn067.
26. Giralt A, Puigdellívol M, Carretón O, Paoletti P, Valero J, Parra-Damas A, et al. Long-term memory deficits in Huntington's disease are associated with reduced CBP histone acetylase activity. Hum Mol Genet 2012; 21:1203-16; PMID:22116937; http://dx.doi.org/10.1093/hmg/ddr552.
27. Romero E, Cha GH, Verstreken P, Ly CV, Hughes RE, Bellen HJ, et al. Suppression of neurodegeneration and increased neurotransmission caused by expanded full-length huntingtin accumulating in the cytoplasm. Neuron 2008; 57:27-40; PMID:18184562; http://dx.doi.org/10.1016/j.neuron.2007.11.025.
28. Taylor JP, Taye AA, Campbell C, Kazemi-Esfarjani P, Fischbeck KH, Min KT. Aberrant histone acetylation, altered transcription, and retinal degeneration in a Drosophila model of polyglutamine disease are rescued by CREB-binding protein. Genes Dev 2003; 17:1463-8; PMID:12815067; http://dx.doi.org/10.1101/gad.1087503.
29. Klevytska AM, Tebbenkamp AT, Savonenko AV, Borchelt DR. Partial depletion of CREB-binding protein reduces life expectancy in a mouse model of Huntington disease. J Neuropathol Exp Neurol 2010; 69:396-404; PMID:20448484; http://dx.doi. org/10.1097/NEN.0b013e3181d6c436.
30. Wang H, Wang L, Erdjument-Bromage H, Vidal M, Tempst P, Jones RS, et al. Role of histone H2A ubiquitination in Polycomb silencing. Nature 2004; 431:873-8; PMID:15386022; http://dx.doi.org/10.1038/nature02985.
31. Kim MO, Chawla P, Overland RP, Xia E, Sadri-Vakili G, Cha JH. Altered histone monoubiquitylation mediated by mutant huntingtin induces transcriptional dysregulation. J Neurosci 2008; 28:3947-57; PMID:18400894; http://dx.doi.org/10.1523/JNEUROSCI.5667-07.2008.
32. Bett JS, Benn CL, Ryu KY, Kopito RR, Bates GP. The polyubiquitin Ubc gene modulates histone H2A monoubiquitylation in the R6/2 mouse model of Huntington's disease. J Cell Mol Med 2009; 13(8B):2645-57; PMID:19602042; http://dx.doi. org/10.1111/j.1582-4934.2008.00543.x.
33. Chong JA, Tapia-Ramírez J, Kim S, Toledo-Aral JJ, Zheng Y, Boutros MC, et al. REST: a mammalian silencer protein that restricts sodium channel gene expression to neurons. Cell 1995; 80:949-57; PMID:7697725; http://dx.doi.org/10.1016/0092-8674(95)90298-8.
34. Schoenherr CJ, Anderson DJ. The neuron-restrictive silencer factor (NRSF): a coordinate repressor of multiple neuron-specific genes. Science 1995; 267:1360-3; PMID:7871435; http://dx.doi.org/10.1126/science. 7871435.
35. Buckley NJ, Johnson R, Zuccato C, Bithell A, Cattaneo E. The role of REST in transcriptional and epigenetic dysregulation in Huntington's disease. Neurobiol Dis 2010; 39:28-39; PMID:20170730; http://dx.doi. org/10.1016/j.nbd.2010.02.003.
36. Ooi L, Wood IC. Chromatin crosstalk in development and disease: lessons from REST. Nat Rev Genet 2007; 8:544-54; PMID:17572692; http://dx.doi. org/10.1038/nrg2100.
37. Zuccato C, Cattaneo E. Role of brain-derived neurotrophic factor in Huntington's disease. Prog Neurobiol 2007; 81:294-330; PMID:17379385; http://dx.doi. org/10.1016/j.pneurobio.2007.01.003.
38. Zuccato C, Cattaneo E. Brain-derived neurotrophic factor in neurodegenerative diseases. Nat Rev Neurol 2009; 5:311-22; PMID:19498435; http://dx.doi. org/10.1038/nrneurol.2009.54.
39. Gehrking KM, Andresen JM, Duvick L, Lough J, Zoghbi HY, Orr HT. Partial loss of Tip60 slows mid-stage neurodegeneration in a spinocerebellar ataxia type 1 (SCA1) mouse model. Hum Mol Genet 2011; 20:2204-12; PMID:21427130; http://dx.doi. org/10.1093/hmg/ddr108.
40. Li F, Macfarlan T, Pittman RN, Chakravarti D. Ataxin-3 is a histone-binding protein with two independent transcriptional corepressor activities. J Biol Chem 2002; 277:45004-12; PMID:12297501; http://dx.doi.org/10.1074/jbc.M205259200.
41. Fiesel FC, Schurr C, Weber SS, Kahle PJ. TDP-43 knockdown impairs neurite outgrowth dependent on its target histone deacetylase 6. Mol Neurodegener 2011; 6:64; PMID:21878116; http://dx.doi. org/10.1186/1750-1326-6-64.
42. Fiesel FC, Voigt A, Weber SS, Van den Haute C, Waldenmaier A, Görner K, et al. Knockdown of transactive response DNA-binding protein (TDP-43) downregulates histone deacetylase 6. EMBO J 2010; 29:209-21; PMID:19910924; http://dx.doi. org/10.1038/emboj.2009.324.
43. Helmlinger D, Hardy S, Eberlin A, Devys D, Tora L. Both normal and polyglutamine-expanded ataxin-7 are components of TFTC-type GCN5 histone acetyltransferase-containing complexes. Biochem Soc Symp 2006; (73):155-63; PMID:16626296.
44. McMahon SJ, Pray-Grant MG, Schieltz D, Yates JR 3rd, Grant PA. Polyglutamine-expanded spinocerebellar ataxia-7 protein disrupts normal SAGA and SLIK histone acetyltransferase activity. Proc Natl Acad Sci USA 2005; 102:8478-82; PMID:15932941; http://dx.doi. org/10.1073/pnas.0503493102.
45. Helmlinger D, Hardy S, Abou-Sleymane G, Eberlin A, Bowman AB, Gansmüller A, et al. Glutamineexpanded ataxin-7 alters TFTC/STAGA recruitment and chromatin structure leading to photoreceptor dysfunction. PLoS Biol 2006; 4:e67; PMID:16494529; http://dx.doi.org/10.1371/journal.pbio.0040067.
46. Palhan VB, Chen S, Peng GH, Tjernberg A, Gamper AM, Fan Y, et al. Polyglutamine-expanded ataxin-7 inhibits STAGA histone acetyltransferase activity to produce retinal degeneration. Proc Natl Acad Sci USA 2005; 102:8472-7; PMID:15932940; http://dx.doi. org/10.1073/pnas.0503505102.
47. Kizilyaprak C, Spehner D, Devys D, Schultz P. The linker histone H1C contributes to the SCA7 nuclear phenotype. Nucleus 2011; 2:444-54; PMID:21970987; http://dx.doi.org/10.4161/nucl.2.5.17843.
48. Chen YC, Gatchel JR, Lewis RW, Mao CA, Grant PA, Zoghbi HY, et al. Gcn5 loss-of-function accelerates cerebellar and retinal degeneration in a SCA7 mouse model. Hum Mol Genet 2012; 21:394-405; PMID:22002997; http://dx.doi.org/10.1093/hmg/ddr474.
49. Sopher BL, Ladd PD, Pineda VV, Libby RT, Sunkin SM, Hurley JB, et al. CTCF regulates ataxin-7 expression through promotion of a convergently transcribed, antisense noncoding RNA. Neuron 2011; 70:1071-84; PMID:21689595; http://dx.doi.org/10.1016/j.neuron. 2011.05.027.
50. Chung DW, Rudnicki DD, Yu L, Margolis RL. A natural antisense transcript at the Huntington's disease repeat locus regulates HTT expression. Hum Mol Genet 2011; 20:3467-77; PMID:21672921; http://dx.doi.org/10.1093/hmg/ddr263.
51. Ikeda Y, Daughters RS, Ranum LP. Bidirectional expression of the SCA8 expansion mutation: one mutation, two genes. Cerebellum 2008; 7:150-8; PMID:18418692; http://dx.doi.org/10.1007/s12311-008-0010-7.
52. Moseley ML, Zu T, Ikeda Y, Gao W, Mosemiller AK, Daughters RS, et al. Bidirectional expression of CUG and CAG expansion transcripts and intranuclear polyglutamine inclusions in spinocerebellar ataxia type 8. Nat Genet 2006; 38:758-69; PMID:16804541; http://dx.doi.org/10.1038/ng1827.
53. de Ruijter AJ, van Gennip AH, Caron HN, Kemp S, van Kuilenburg AB. Histone deacetylases (HDACs): characterization of the classical HDAC family. Biochem J 2003; 370:737-49; PMID:12429021; http://dx.doi. org/10.1042/BJ20021321.
54. Marks PA, Xu WS. Histone deacetylase inhibitors: Potential in cancer therapy. J Cell Biochem 2009; 107:600-8; PMID:19459166; http://dx.doi. org/10.1002/jcb.22185.
55. Parmigiani RB, Xu WS, Venta-Perez G, Erdjument-Bromage H, Yaneva M, Tempst P, et al. HDAC6 is a specific deacetylase of peroxiredoxins and is involved in redox regulation. Proc Natl Acad Sci USA 2008; 105:9633-8; PMID:18606987; http://dx.doi. org/10.1073/pnas.0803749105.
56. Richon VM, Zhou X, Rifkind RA, Marks PA. Histone deacetylase inhibitors: development of suberoylanilide hydroxamic acid (SAHA) for the treatment of cancers. Blood Cells Mol Dis 2001; 27:260-4; PMID:11358386; http://dx.doi.org/10.1006/bcmd.2000.0376.
57. Hockly E, Richon VM, Woodman B, Smith DL, Zhou X, Rosa E, et al. Suberoylanilide hydroxamic acid, a histone deacetylase inhibitor, ameliorates motor deficits in a mouse model of Huntington's disease. Proc Natl Acad Sci USA 2003; 100:2041-6; PMID:12576549; http://dx.doi.org/10.1073/pnas.0437870100.
58. Mielcarek M, Benn CL, Franklin SA, Smith DL, Woodman B, Marks PA, et al. SAHA decreases HDAC 2 and 4 levels in vivo and improves molecular phenotypes in the R6/2 mouse model of Huntington's disease. PLoS ONE 2011; 6:e27746; PMID:22140466; http://dx.doi.org/10.1371/journal.pone.0027746.
59. Giorgini F, Möller T, Kwan W, Zwilling D, Wacker JL, Hong S, et al. Histone deacetylase inhibition modulates kynurenine pathway activation in yeast, microglia, and mice expressing a mutant huntingtin fragment. J Biol Chem 2008; 283:7390-400; PMID:18079112; http://dx.doi.org/10.1074/jbc.M708192200.
60. Chou AH, Chen SY, Yeh TH, Weng YH, Wang HL. HDAC inhibitor sodium butyrate reverses transcriptional downregulation and ameliorates ataxic symptoms in a transgenic mouse model of SCA3. Neurobiol Dis 2011; 41:481-8; PMID:21047555; http://dx.doi. org/10.1016/j.nbd.2010.10.019.
61. Thomas EA, Coppola G, Desplats PA, Tang B, Soragni E, Burnett R, et al. The HDAC inhibitor 4b ameliorates the disease phenotype and transcriptional abnormalities in Huntington's disease transgenic mice. Proc Natl Acad Sci USA 2008; 105:15564-9; PMID:18829438; http://dx.doi.org/10.1073/pnas.0804249105.
62. Jia H, Pallos J, Jacques V, Lau A, Tang B, Cooper A, et al. Histone deacetylase (HDAC) inhibitors targeting HDAC3 and HDAC1 ameliorate polyglutamine-elicited phenotypes in model systems of Huntington's disease. Neurobiol Dis 2012; 46:351-61; PMID:22590724; http://dx.doi.org/10.1016/j. nbd.2012.01.016.
63. Pallos J, Bodai L, Lukacsovich T, Purcell JM, Steffan JS, Thompson LM, et al. Inhibition of specific HDACs and sirtuins suppresses pathogenesis in a Drosophila model of Huntington's disease. Hum Mol Genet 2008; 17:3767-75; PMID:18762557; http://dx.doi. org/10.1093/hmg/ddn273.
64. Jiang M, Wang J, Fu J, Du L, Jeong H, West T, et al. Neuroprotective role of Sirt1 in mammalian models of Huntington's disease through activation of multiple Sirt1 targets. Nat Med 2012; 18:153-8; PMID:22179319; http://dx.doi.org/10.1038/nm.2558.
65. Benn CL, Butler R, Mariner L, Nixon J, Moffitt H, Mielcarek M, et al. Genetic knock-down of HDAC7 does not ameliorate disease pathogenesis in the R6/2 mouse model of Huntington's disease. PLoS ONE 2009; 4:e5747; PMID:19484127; http://dx.doi. org/10.1371/journal.pone.0005747.
66. Moumné L, Campbell K, Howland D, Ouyang Y, Bates GP. Genetic knock-down of HDAC3 does not modify disease-related phenotypes in a mouse model of Huntington's disease. PLoS ONE 2012; 7:e31080; PMID:22347433; http://dx.doi.org/10.1371/journal. pone.0031080.
67. Bobrowska A, Paganetti P, Matthias P, Bates GP. Hdac6 knock-out increases tubulin acetylation but does not modify disease progression in the R6/2 mouse model of Huntington's disease. PLoS ONE 2011; 6:e20696; PMID:21677773; http://dx.doi.org/10.1371/journal. pone.0020696.
68. Thomson JA, Itskovitz-Eldor J, Shapiro SS, Waknitz MA, Swiergiel JJ, Marshall VS, et al. Embryonic stem cell lines derived from human blastocysts. Science 1998; 282:1145-7; PMID:9804556; http://dx.doi. org/10.1126/science.282.5391.1145.
69. Takahashi K, Yamanaka S. Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors. Cell 2006; 126:663-76; PMID:16904174; http://dx.doi.org/10.1016/j. cell.2006.07.024.
70. Urbach A, Bar-Nur O, Daley GQ, Benvenisty N. Differential modeling of fragile X syndrome by human embryonic stem cells and induced pluripotent stem cells. Cell Stem Cell 2010; 6:407-11; PMID:20452313; http://dx.doi.org/10.1016/j.stem.2010.04.005.
71. Benchoua A, Onteniente B. Intracerebral transplantation for neurological disorders. Lessons from developmental, experimental, and clinical studies. Front Cell Neurosci 2011; 6:2; PMID:22319470.
72. Aubry L, Bugi A, Lefort N, Rousseau F, Peschanski M, Perrier AL. Striatal progenitors derived from human ES cells mature into DARPP32 neurons in vitro and in quinolinic acid-lesioned rats. Proc Natl Acad Sci USA 2008; 105:16707-12; PMID:18922775; http://dx.doi. org/10.1073/pnas.0808488105.
73. Chambers SM, Fasano CA, Papapetrou EP, Tomishima M, Sadelain M, Studer L. Highly efficient neural conversion of human ES and iPS cells by dual inhibition of SMAD signaling. Nat Biotechnol 2009; 27:275-80; PMID:19252484; http://dx.doi.org/10.1038/nbt.1529.
74. Hu BY, Weick JP, Yu J, Ma LX, Zhang XQ, Thomson JA, et al. Neural differentiation of human induced pluripotent stem cells follows developmental principles but with variable potency. Proc Natl Acad Sci USA 2010; 107:4335-40; PMID:20160098; http://dx.doi. org/10.1073/pnas.0910012107.
75. Kozhich OA, Hamilton RS, Mallon BS. Standardized Generation and Differentiation of Neural Precursor Cells from Human Pluripotent Stem Cells. Stem Cell Rev 2012; PMID:22388559; http://dx.doi. org/10.1007/s12015-012-9357-8.
76. Lie KH, Chung HC, Sidhu KS. Derivation, propagation, and characterization of neuroprogenitors from pluripotent stem cells (hESCs and hiPSCs). Methods Mol Biol 2012; 873:237-46; PMID:22528359; http://dx.doi.org/10.1007/978-1-61779-794-1-15.
77. Chan AW, Cheng PH, Neumann A, Yang JJ. Reprogramming Huntington monkey skin cells into pluripotent stem cells. Cell Reprogram 2010; 12:509-17; PMID:20936902; http://dx.doi.org/10.1089/cell.2010.0019.
78. Camnasio S, Carri AD, Lombardo A, Grad I, Mariotti C, Castucci A, et al. The first reported generation of several induced pluripotent stem cell lines from homozygous and heterozygous Huntington's disease patients demonstrates mutation related enhanced lysosomal activity. Neurobiol Dis 2012; 46:41-51; PMID:22405424; http://dx.doi.org/10.1016/j. nbd.2011.12.042.
79. Castiglioni V, Onorati M, Rochon C, Cattaneo E. Induced pluripotent stem cell lines from Huntington's disease mice undergo neuronal differentiation while showing alterations in the lysosomal pathway. Neurobiol Dis 2012; 46:30-40; PMID:22227000; http://dx.doi.org/10.1016/j.nbd.2011.12.032.
80. Zhang N, An MC, Montoro D, Ellerby LM. Characterization of Human Huntington's Disease Cell Model from Induced Pluripotent Stem Cells. PLoS Curr 2010; 2:RRN1193; PMID:21037797; http://dx.doi.org/10.1371/currents.RRN1193.
81. Juopperi TA, Kim WR, Chiang CH, Yu H, Margolis RL, Ross CA, et al. Astrocytes generated from patient induced pluripotent stem cells recapitulate features of Huntington's disease patient cells. Mol Brain 2012; 5:17; PMID:22613578; http://dx.doi. org/10.1186/1756-6606-5-17.
82. Jeon I, Lee N, Li JY, Park IH, Park KS, Moon J, et al. Neuronal Properties, In Vivo Effects and Pathology of a Huntington's Disease Patient-Derived Induced Pluripotent Stem Cells. Stem Cells 2012; PMID:22628015; http://dx.doi.org/10.1002/stem.1135.
83. Koch P, Breuer P, Peitz M, Jungverdorben J, Kesavan J, Poppe D, et al. Excitation-induced ataxin-3 aggregation in neurons from patients with Machado-Joseph disease. Nature 2011; 480:543-6; PMID:22113611.
84. Narsinh KH, Plews J, Wu JC. Comparison of human induced pluripotent and embryonic stem cells: fraternal or identical twins? Mol Ther 2011; 19:635-8; PMID:21455209; http://dx.doi.org/10.1038/mt.2011.41.
85. Osafune K, Caron L, Borowiak M, Martinez RJ, Fitz-Gerald CS, Sato Y, et al. Marked differences in differentiation propensity among human embryonic stem cell lines. Nat Biotechnol 2008; 26:313-5; PMID:18278034; http://dx.doi.org/10.1038/nbt1383.
86. Pick M, Stelzer Y, Bar-Nur O, Mayshar Y, Eden A, Benvenisty N. Clone-and gene-specific aberrations of parental imprinting in human induced pluripotent stem cells. Stem Cells 2009; 27:2686-90; PMID:19711451; http://dx.doi.org/10.1002/stem.205.
87. Rugg-Gunn PJ, Ferguson-Smith AC, Pedersen RA. Status of genomic imprinting in human embryonic stem cells as revealed by a large cohort of independently derived and maintained lines. Hum Mol Genet 2007; 16 Spec No. 2:R243-51; PMID:17911167; http://dx.doi.org/10.1093/hmg/ddm245.
88. Caiazzo M, Dell'Anno MT, Dvoretskova E, Lazarevic D, Taverna S, Leo D, et al. Direct generation of functional dopaminergic neurons from mouse and human fibroblasts. Nature 2011; 476:224-7; PMID:21725324; http://dx.doi.org/10.1038/nature10284.
89. Pang ZP, Yang N, Vierbuchen T, Ostermeier A, Fuentes DR, Yang TQ, et al. Induction of human neuronal cells by defined transcription factors. Nature 2011; 476:220-3; PMID:21617644.
90. Pfisterer U, Wood J, Nihlberg K, Hallgren O, Bjermer L, Westergren-Thorsson G, et al. Efficient induction of functional neurons from adult human fibroblasts. Cell Cycle 2011; 10:3311-6; PMID:21934358; http://dx.doi.org/10.4161/cc.10.19.17584.
91. Qiang L, Fujita R, Yamashita T, Angulo S, Rhinn H, Rhee D, et al. Directed conversion of Alzheimer's disease patient skin fibroblasts into functional neurons. Cell 2011; 146:359-71; PMID:21816272; http://dx.doi.org/10.1016/j.cell.2011.07.007.
92. Yoo AS, Sun AX, Li L, Shcheglovitov A, Portmann T, Li Y, et al. MicroRNA-mediated conversion of human fibroblasts to neurons. Nature 2011; 476:228-31; PMID:21753754; http://dx.doi.org/10.1038/nature10323.
93. Brennand KJ, Simone A, Jou J, Gelboin-Burkhart C, Tran N, Sangar S, et al. Modelling schizophrenia using human induced pluripotent stem cells. Nature 2011; 473:221-5; PMID:21490598; http://dx.doi. org/10.1038/nature09915.
94. Di Giorgio FP, Boulting GL, Bobrowicz S, Eggan KC. Human embryonic stem cell-derived motor neurons are sensitive to the toxic effect of glial cells carrying an ALS-causing mutation. Cell Stem Cell 2008; 3:637-48; PMID:19041780; http://dx.doi.org/10.1016/j. stem.2008.09.017.
95. Lee G, Papapetrou EP, Kim H, Chambers SM, Tomishima MJ, Fasano CA, et al. Modelling pathogenesis and treatment of familial dysautonomia using patient-specific iPSCs. Nature 2009; 461:402-6; PMID:19693009; http://dx.doi.org/10.1038/nature08320.
96. Marchetto MC, Muotri AR, Mu Y, Smith AM, Cezar GG, Gage FH. Non-cell-autonomous effect of human SOD1 G37R astrocytes on motor neurons derived from human embryonic stem cells. Cell Stem Cell 2008; 3:649-57; PMID:19041781; http://dx.doi. org/10.1016/j.stem.2008.10.001.