Aberrant epigenome in iPSC-derived dopaminergic neurons from Parkinson's disease patients

EMBO Molecular Medicine

Volumn 7, Issue 12, 2015, Pages 1529-1546

  Fernández Santiago, Rubén ^a,b   Carballo Carbajal, Iria ^b,c   Castellano, Giancarlo ^a   Torrent, Roger ^a   Richaud, Yvonne ^d,e   Sánchez Danés, Adriana ^a   Vilarrasa Blasi, Roser ^a   Sánchez Pla, Alex ^a,f   Mosquera, José Luis ^a   Soriano, Jordi ^a   López Barneo, José ^b,g   Canals, Josep M ^a,b,h   Alberch, Jordi ^a,b,h   Raya, Ángel ^d,e,i   Vila, Miquel ^b,c,i   Consiglio, Antonella ^a,j   Martín Subero, José I ^a   Ezquerra, Mario ^a,b   Tolosa, Eduardo ^a,b  

^a UNIVERSITY OF BARCELONA   (Spain)

^b CENTRO DE INVESTIGACIÓN BIOMÉDICA EN RED SOBRE ENFERMEDADES NEURODEGENERATIVAS CIBERNED   (Spain)

^c UNIVERSITAT AUTÒNOMA DE BARCELONA   (Spain)

^d INSTITUTE FOR BIOENGINEERING OF CATALONIA IBEC   (Spain)

^e BIOMATERIALES Y NANOMEDICINA CIBER BBN   (Spain)

^f HOSPITAL UNIVERSITARI VALL D HEBRON   (Spain)

^g HOSPITAL UNIVERSITARIO VIRGEN DEL ROCÍO   (Spain)

^h UNIVERSITY OF BARCELONA   (Spain)

ⁱ INSTITUCIÓ CATALANA DE RECERCA I ESTUDIS AVANÇATS ICREA   (Spain)

^j UNIVERSITY OF BRESCIA   (Italy)

more..

Author keywords

DNA methylation; Dopaminergic neuron; Induced pluripotent stem cell; Parkinson's disease; Transcription factor

Indexed keywords

HEPATOCYTE NUCLEAR FACTOR 3ALPHA; LEUCINE RICH REPEAT KINASE 2; RNA; TRANSCRIPTION FACTOR; TRANSCRIPTION FACTOR FOSL2; TRANSCRIPTION FACTOR HNF4A; TRANSCRIPTION FACTOR NR3C1; TRANSCRIPTOME; UNCLASSIFIED DRUG; LRRK2 PROTEIN, HUMAN; PROTEIN SERINE THREONINE KINASE;

ARTICLE; CELL DIFFERENTIATION; CONTROLLED STUDY; DNA METHYLATION; DOPAMINERGIC NERVE CELL; DOWN REGULATION; ENHANCER REGION; EPIGENETICS; GENE EXPRESSION; HUMAN; HUMAN CELL; MONOGENIC DISORDER; NUCLEAR REPROGRAMMING; PARKINSON DISEASE; PLURIPOTENT STEM CELL; PRIORITY JOURNAL; SKIN CELL; SOMATIC CELL; STEM CELL CULTURE; GENE EXPRESSION PROFILING; GENETICS; INDUCED PLURIPOTENT STEM CELL; METABOLISM; PHYSIOLOGY;

CELLULAR REPROGRAMMING; DNA METHYLATION; DOPAMINERGIC NEURONS; EPIGENOMICS; GENE EXPRESSION PROFILING; HUMANS; INDUCED PLURIPOTENT STEM CELLS; LEUCINE-RICH REPEAT SERINE-THREONINE PROTEIN KINASE-2; PARKINSON DISEASE; PROTEIN-SERINE-THREONINE KINASES;

EID: 84954387478     PISSN: 17574676     EISSN: 17574684     Source Type: Journal    
DOI: 10.15252/emmm.201505439     Document Type: Article

References (76)

1. Agirre X, Castellano G, Pascual M, Heath S, Kulis M, Segura V, Bergmann A, Esteve A, Merkel A, Raineri E et al (2015) Whole-epigenome analysis in multiple myeloma reveals DNA hypermethylation of B cell-specific enhancers. Genome Res 25: 478-487
2. Ambrosi G, Ghezzi C, Sepe S, Milanese C, Payan-Gomez C, Bombardieri CR, Armentero MT, Zangaglia R, Pacchetti C, Mastroberardino PG et al (2014) Bioenergetic and proteolytic defects in fibroblasts from patients with sporadic Parkinson's disease. Biochim Biophys Acta 1842: 1385-1394
3. Beach TG, Adler CH, Sue LI, Vedders L, Lue L, White Iii CL, Akiyama H, Caviness JN, Shill HA, Sabbagh MN et al (2010) Multi-organ distribution of phosphorylated alpha-synuclein histopathology in subjects with Lewy body disorders. Acta Neuropathol 119: 689-702
4. Benjamini Y (1995) Controlling the false discovery rate: a practical and powerful approach to multiple testing. J R Stat Series B 57: 289-300
5. Bergman Y, Cedar H (2013) DNA methylation dynamics in health and disease. Nat Struct Mol Biol 20: 274-281
6. Bibikova M, Barnes B, Tsan C, Ho V, Klotzle B, Le JM, Delano D, Zhang L, Schroth GP, Gunderson KL et al (2011) High density DNA methylation array with single CpG site resolution. Genomics 98: 288-295
7. de Boni L, Tierling S, Roeber S, Walter J, Giese A, Kretzschmar HA (2011) Next-generation sequencing reveals regional differences of the alpha-synuclein methylation state independent of Lewy body disease. Neuromolecular Med 13: 310-320
8. Byers B, Cord B, Nguyen HN, Schule B, Fenno L, Lee PC, Deisseroth K, Langston JW, Pera RR, Palmer TD (2011) SNCA triplication Parkinson's patient's iPSC-derived DA neurons accumulate alpha-synuclein and are susceptible to oxidative stress. PLoS ONE 6: e26159
9. Cao X, Yasuda T, Uthayathas S, Watts RL, Mouradian MM, Mochizuki H, Papa SM (2010) Striatal overexpression of DeltaFosB reproduces chronic levodopa-induced involuntary movements. J Neurosci 30: 7335-7343
10. Cooper O, Seo H, Andrabi S, Guardia-Laguarta C, Graziotto J, Sundberg M, McLean JR, Carrillo-Reid L, Xie Z, Osborn T et al (2012) Pharmacological rescue of mitochondrial deficits in iPSC-derived neural cells from patients with familial Parkinson's disease. Sci Transl Med 4: 141ra190
11. Desplats P, Spencer B, Coffee E, Patel P, Michael S, Patrick C, Adame A, Rockenstein E, Masliah E (2011) Alpha-synuclein sequesters Dnmt1 from the nucleus: a novel mechanism for epigenetic alterations in Lewy body diseases. J Biol Chem 286: 9031-9037
12. Di Fonzo A, Rohe CF, Ferreira J, Chien HF, Vacca L, Stocchi F, Guedes L, Fabrizio E, Manfredi M, Vanacore N et al (2005) A frequent LRRK2 gene mutation associated with autosomal dominant Parkinson's disease. Lancet 365: 412-415
13. Doi A, Park IH, Wen B, Murakami P, Aryee MJ, Irizarry R, Herb B, Ladd-Acosta C, Rho J, Loewer S et al (2009) Differential methylation of tissue- and cancer-specific CpG island shores distinguishes human induced pluripotent stem cells, embryonic stem cells and fibroblasts. Nat Genet 41: 1350-1353
14. Domanskyi A, Alter H, Vogt MA, Gass P, Vinnikov IA (2014) Transcription factors Foxa1 and Foxa2 are required for adult dopamine neurons maintenance. Front Cell Neurosci 8: 275
15. Dunham I, Kundaje A, Aldred SF, Collins PJ, Davis CA, Doyle F, Epstein CB, Frietze S, Harrow J, Kaul R et al (2012) An integrated encyclopedia of DNA elements in the human genome. Nature 489: 57-74
16. Ernst J, Kheradpour P, Mikkelsen TS, Shoresh N, Ward LD, Epstein CB, Zhang X, Wang L, Issner R, Coyne M et al (2011) Mapping and analysis of chromatin state dynamics in nine human cell types. Nature 473: 43-49
17. Escott-Price V, Nalls MA, Morris HR, Lubbe S, Brice A, Gasser T, Heutink P, Wood NW, Hardy J, Singleton AB et al (2015) Polygenic risk of Parkinson disease is correlated with disease age at onset. Ann Neurol 77: 582-591
18. Farrer MJ (2006) Genetics of Parkinson disease: paradigm shifts and future prospects. Nat Rev Genet 7: 306-318
19. Feil R, Fraga MF (2011) Epigenetics and the environment: emerging patterns and implications. Nat Rev Genet 13: 97-109
20. Gerstein MB, Kundaje A, Hariharan M, Landt SG, Yan KK, Cheng C, Mu XJ, Khurana E, Rozowsky J, Alexander R et al (2012) Architecture of the human regulatory network derived from ENCODE data. Nature 489: 91-100
21. Gilks WP, Abou-Sleiman PM, Gandhi S, Jain S, Singleton A, Lees AJ, Shaw K, Bhatia KP, Bonifati V, Quinn NP et al (2005) A common LRRK2 mutation in idiopathic Parkinson's disease. Lancet 365: 415-416
22. Goedert M, Jakes R, Crowther RA, Six J, Lubke U, Vandermeeren M, Cras P, Trojanowski JQ, Lee VM (1993) The abnormal phosphorylation of tau protein at Ser-202 in Alzheimer disease recapitulates phosphorylation during development. Proc Natl Acad Sci USA 90: 5066-5070
23. Healy DG, Falchi M, O'Sullivan SS, Bonifati V, Durr A, Bressman S, Brice A, Aasly J, Zabetian CP, Goldwurm S et al (2008) Phenotype, genotype, and worldwide genetic penetrance of LRRK2-associated Parkinson's disease: a case-control study. Lancet Neurol 7: 583-590
24. van Heesbeen HJ, Mesman S, Veenvliet JV, Smidt MP (2013) Epigenetic mechanisms in the development and maintenance of dopaminergic neurons. Development 140: 1159-1169
25. Hochedlinger K, Plath K (2009) Epigenetic reprogramming and induced pluripotency. Development 136: 509-523
26. Hoepken HH, Gispert S, Azizov M, Klinkenberg M, Ricciardi F, Kurz A, Morales-Gordo B, Bonin M, Riess O, Gasser T et al (2008) Parkinson patient fibroblasts show increased alpha-synuclein expression. Exp Neurol 212: 307-313
27. Holmberg J, Perlmann T (2012) Maintaining differentiated cellular identity. Nat Rev Genet 13: 429-439
28. Hon GC, Rajagopal N, Shen Y, McCleary DF, Yue F, Dang MD, Ren B (2013) Epigenetic memory at embryonic enhancers identified in DNA methylation maps from adult mouse tissues. Nat Genet 45: 1198-1206
29. Huang da, Sherman BT, Lempicki RA (2009) Systematic and integrative analysis of large gene lists using DAVID bioinformatics resources. Nat Protoc 4: 44-57
30. IPDGC (2011) A two-stage meta-analysis identifies several new loci for Parkinson's disease. PLoS Genet 7: e1002142
31. Irizarry RA, Hobbs B, Collin F, Beazer-Barclay YD, Antonellis KJ, Scherf U, Speed TP (2003) Exploration, normalization, and summaries of high density oligonucleotide array probe level data. Biostatistics 4: 249-264
32. Jiang H, Ren Y, Yuen EY, Zhong P, Ghaedi M, Hu Z, Azabdaftari G, Nakaso K, Yan Z, Feng J (2012) Parkin controls dopamine utilization in human midbrain dopaminergic neurons derived from induced pluripotent stem cells. Nat Commun 3: 668
33. Jin H, Kanthasamy A, Harischandra DS, Kondru N, Ghosh A, Panicker N, Anantharam V, Rana A, Kanthasamy AG (2014) Histone hyperacetylation upregulates pkcdelta in dopaminergic neurons to induce cell death: relevance to epigenetic mechanisms of neurodegeneration in Parkinson's disease. J Biol Chem 289: 34743-34767
34. Jones PA (2012) Functions of DNA methylation: islands, start sites, gene bodies and beyond. Nat Rev Genet 13: 484-492
35. Kontopoulos E, Parvin JD, Feany MB (2006) Alpha-synuclein acts in the nucleus to inhibit histone acetylation and promote neurotoxicity. Hum Mol Genet 15: 3012-3023
36. Kulis M, Heath S, Bibikova M, Queiros AC, Navarro A, Clot G, Martinez-Trillos A, Castellano G, Brun-Heath I, Pinyol M et al (2012) Epigenomic analysis detects widespread gene-body DNA hypomethylation in chronic lymphocytic leukemia. Nat Genet 44: 1236-1242
37. Kulis M, Queiros AC, Beekman R, Martin-Subero JI (2013) Intragenic DNA methylation in transcriptional regulation, normal differentiation and cancer. Biochim Biophys Acta 1829: 1161-1174
38. Laguna A, Schintu N, Nobre A, Alvarsson A, Volakakis N, Jacobsen JK, Gomez-Galan M, Sopova E, Joodmardi E, Yoshitake T et al (2015) Dopaminergic control of autophagic-lysosomal function implicates Lmx1b in Parkinson's disease. Nat Neurosci 18: 826-835
39. Lahti L, Saarimaki-Vire J, Rita H, Partanen J (2011) FGF signaling gradient maintains symmetrical proliferative divisions of midbrain neuronal progenitors. Dev Biol 349: 270-282
40. Lahti L, Peltopuro P, Piepponen TP, Partanen J (2012) Cell-autonomous FGF signaling regulates anteroposterior patterning and neuronal differentiation in the mesodiencephalic dopaminergic progenitor domain. Development 139: 894-905
41. Lang AE, Lozano AM (1998a) Parkinson's disease. First of two parts. N Engl J Med 339: 1044-1053
42. Lang AE, Lozano AM (1998b) Parkinson's disease. Second of two parts. N Engl J Med 339: 1130-1143
43. Lee ST, Xiao Y, Muench MO, Xiao J, Fomin ME, Wiencke JK, Zheng S, Dou X, de Smith A, Chokkalingam A et al (2012) A global DNA methylation and gene expression analysis of early human B-cell development reveals a demethylation signature and transcription factor network. Nucleic Acids Res 40: 11339-11351
44. Lesage S, Durr A, Tazir M, Lohmann E, Leutenegger AL, Janin S, Pollak P, Brice A (2006) LRRK2 G2019S as a cause of Parkinson's disease in North African Arabs. N Engl J Med 354: 422-423
45. Lindvall O, Bjorklund A (2011) Cell therapeutics in Parkinson's disease. Neurotherapeutics 8: 539-548
46. Masliah E, Dumaop W, Galasko D, Desplats P (2013) Distinctive patterns of DNA methylation associated with Parkinson disease: identification of concordant epigenetic changes in brain and peripheral blood leukocytes. Epigenetics 8: 1030-1038
47. Morizane A, Doi D, Kikuchi T, Okita K, Hotta A, Kawasaki T, Hayashi T, Onoe H, Shiina T, Yamanaka S et al (2013) Direct comparison of autologous and allogenic transplantation of iPSC derived neural cells in the brain of a nonhuman primate. Stem Cell Rep 1: 283-292
48. Nalls MA, Pankratz N, Lill CM, Do CB, Hernandez DG, Saad M, DeStefano AL, Kara E, Bras J, Sharma M et al (2014) Large-scale meta-analysis of genome-wide association data identifies six new risk loci for Parkinson's disease. Nat Genet 46: 989-993
49. Nguyen HN, Byers B, Cord B, Shcheglovitov A, Byrne J, Gujar P, Kee K, Schule B, Dolmetsch RE, Langston W et al (2011) LRRK2 mutant iPSC-derived DA neurons demonstrate increased susceptibility to oxidative stress. Cell Stem Cell 8: 267-280
50. Nikolaev A, McLaughlin T, O'Leary DD, Tessier-Lavigne M (2009) APP binds DR6 to trigger axon pruning and neuron death via distinct caspases. Nature 457: 981-989
51. Orenstein SJ, Kuo SH, Tasset I, Arias E, Koga H, Fernandez-Carasa I, Cortes E, Honig LS, Dauer W, Consiglio A et al (2013) Interplay of LRRK2 with chaperone-mediated autophagy. Nat Neurosci 16: 394-406
52. Ozelius LJ, Senthil G, Saunders-Pullman R, Ohmann E, Deligtisch A, Tagliati M, Hunt AL, Klein C, Henick B, Hailpern SM et al (2006) LRRK2 G2019S as a cause of Parkinson's disease in Ashkenazi Jews. N Engl J Med 354: 424-425
53. Paisan-Ruiz C, Jain S, Evans EW, Gilks WP, Simon J, van der Brug M, Lopez de Munain A, Aparicio S, Gil AM, Khan N et al (2004) Cloning of the gene containing mutations that cause PARK8-linked Parkinson's disease. Neuron 44: 595-600
54. Papkovskaia TD, Chau KY, Inesta-Vaquera F, Papkovsky DB, Healy DG, Nishio K, Staddon J, Duchen MR, Hardy J, Schapira AH et al (2012) G2019S leucine-rich repeat kinase 2 causes uncoupling protein-mediated mitochondrial depolarization. Hum Mol Genet 21: 4201-4213
55. Pieper HC, Evert BO, Kaut O, Riederer PF, Waha A, Wullner U (2008) Different methylation of the TNF-alpha promoter in cortex and substantia nigra: implications for selective neuronal vulnerability. Neurobiol Dis 32: 521-527
56. Potashkin JA, Santiago JA, Ravina BM, Watts A, Leontovich AA (2012) Biosignatures for Parkinson's disease and atypical parkinsonian disorders patients. PLoS ONE 7: e43595
57. Rakovic A, Shurkewitsch K, Seibler P, Grunewald A, Zanon A, Hagenah J, Krainc D, Klein C (2013) Phosphatase and tensin homolog (PTEN)-induced putative kinase 1 (PINK1)-dependent ubiquitination of endogenous Parkin attenuates mitophagy: study in human primary fibroblasts and induced pluripotent stem cell-derived neurons. J Biol Chem 288: 2223-2237
58. Reinhardt P, Schmid B, Burbulla LF, Schondorf DC, Wagner L, Glatza M, Hoing S, Hargus G, Heck SA, Dhingra A et al (2013) 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
59. Ros-Bernal F, Hunot S, Herrero MT, Parnadeau S, Corvol JC, Lu L, Alvarez-Fischer D, Carrillo-de Sauvage MA, Saurini F, Coussieu C et al (2011) Microglial glucocorticoid receptors play a pivotal role in regulating dopaminergic neurodegeneration in parkinsonism. Proc Natl Acad Sci USA 108: 6632-6637
60. Ryan SD, Dolatabadi N, Chan SF, Zhang X, Akhtar MW, Parker J, Soldner F, Sunico CR, Nagar S, Talantova M et al (2013) Isogenic human iPSC Parkinson's model shows nitrosative stress-induced dysfunction in MEF2-PGC1alpha transcription. Cell 155: 1351-1364
61. Sanchez-Danes A, Consiglio A, Richaud Y, Rodriguez-Piza I, Dehay B, Edel M, Bove J, Memo M, Vila M, Raya A et al (2012a) Efficient generation of A9 midbrain dopaminergic neurons by lentiviral delivery of LMX1A in human embryonic stem cells and induced pluripotent stem cells. Hum Gene Ther 23: 56-69
62. Sanchez-Danes A, Richaud-Patin Y, Carballo-Carbajal I, Jimenez-Delgado S, Caig C, Mora S, Di Guglielmo C, Ezquerra M, Patel B, Giralt A et al (2012b) Disease-specific phenotypes in dopamine neurons from human iPS-based models of genetic and sporadic Parkinson's disease. EMBO Mol Med 4: 380-395
63. Santiago JA, Potashkin JA (2015) Network-based metaanalysis identifies HNF4A and PTBP1 as longitudinally dynamic biomarkers for Parkinson's disease. Proc Natl Acad Sci USA 112: 2257-2262
64. Schafer DP, Stevens B (2010) Synapse elimination during development and disease: immune molecules take centre stage. Biochem Soc Trans 38: 476-481
65. Schondorf DC, Aureli M, McAllister FE, Hindley CJ, Mayer F, Schmid B, Sardi SP, Valsecchi M, Hoffmann S, Schwarz LK et al (2014) iPSC-derived neurons from GBA1-associated Parkinson's disease patients show autophagic defects and impaired calcium homeostasis. Nat Commun 5: 4028
66. Seibler P, Graziotto J, Jeong H, Simunovic F, Klein C, Krainc D (2011) Mitochondrial Parkin recruitment is impaired in neurons derived from mutant PINK1 induced pluripotent stem cells. J Neurosci 31: 5970-5976
67. Shannon KM, Keshavarzian A, Mutlu E, Dodiya HB, Daian D, Jaglin JA, Kordower JH (2012) Alpha-synuclein in colonic submucosa in early untreated Parkinson's disease. Mov Disord 27: 709-715
68. Smyth GK (2004) Linear models and empirical bayes methods for assessing differential expression in microarray experiments. Stat Appl Genet Mol Biol 3: Article3
69. Stadler MB, Murr R, Burger L, Ivanek R, Lienert F, Scholer A, van Nimwegen E, Wirbelauer C, Oakeley EJ, Gaidatzis D et al (2011) DNA-binding factors shape the mouse methylome at distal regulatory regions. Nature 480: 490-495
70. Stott SR, Metzakopian E, Lin W, Kaestner KH, Hen R, Ang SL (2013) Foxa1 and foxa2 are required for the maintenance of dopaminergic properties in ventral midbrain neurons at late embryonic stages. J Neurosci 33: 8022-8034
71. Urdinguio RG, Sanchez-Mut JV, Esteller M (2009) Epigenetic mechanisms in neurological diseases: genes, syndromes, and therapies. Lancet Neurol 8: 1056-1072
72. Xie M, Hong C, Zhang B, Lowdon RF, Xing X, Li D, Zhou X, Lee HJ, Maire CL, Ligon KL et al (2013) DNA hypomethylation within specific transposable element families associates with tissue-specific enhancer landscape. Nat Genet 45: 836-841
73. Yakhine-Diop SM, Bravo-San Pedro JM, Gomez-Sanchez R, Pizarro-Estrella E, Rodriguez-Arribas M, Climent V, Aiastui A, Lopez de Munain A, Fuentes JM, Gonzalez-Polo RA (2014) G2019S LRRK2 mutant fibroblasts from Parkinson's disease patients show increased sensitivity to neurotoxin 1-methyl-4-phenylpyridinium dependent of autophagy. Toxicology 324: 1-9
74. Zhu H, Lensch MW, Cahan P, Daley GQ (2011) Investigating monogenic and complex diseases with pluripotent stem cells. Nat Rev Genet 12: 266-275
75. Ziller MJ, Gu H, Muller F, Donaghey J, Tsai LT, Kohlbacher O, De Jager PL, Rosen ED, Bennett DA, Bernstein BE et al (2013) Charting a dynamic DNA methylation landscape of the human genome. Nature 500: 477-481
76. Zimprich A, Biskup S, Leitner P, Lichtner P, Farrer M, Lincoln S, Kachergus J, Hulihan M, Uitti RJ, Calne DB et al (2004) Mutations in LRRK2 cause autosomal-dominant Parkinsonism with pleomorphic pathology. Neuron 44: 601-607