RNA sequence analysis of human huntington disease brain reveals an extensive increase in inflammatory and developmental gene expression

PLoS ONE

Volumn 10, Issue 12, 2015, Pages

  Labadorf, Adam ^a,b   Hoss, Andrew G ^a   Lagomarsino, Valentina ^a   Latourelle, Jeanne C ^a   Hadzi, Tiffany C ^a   Bregu, Joli ^a   MacDonald, Marcy E ^c   Gusella, James F ^c   Chen, Jiang Fan ^a   Akbarian, Schahram ^d   Weng, Zhiping ^e   Myers, Richard H ^a,b  

^a BOSTON UNIVERSITY SCHOOL OF MEDICINE   (United States)

^b BOSTON UNIVERSITY   (United States)

^c MASSACHUSETTS GENERAL HOSPITAL   (United States)

^d MOUNT SINAI SCHOOL OF MEDICINE   (United States)

^e UNIVERSITY OF MASSACHUSETTS MEDICAL SCHOOL   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

MESSENGER RNA;

ADULT; ARTICLE; BRAIN CELL; BRAIN REGION; CLINICAL ARTICLE; CONTROLLED STUDY; GENE EXPRESSION REGULATION; GENOME ANALYSIS; HIGH THROUGHPUT SEQUENCING; HOMEOBOX; HOX GENE; HUMAN; HUMAN TISSUE; HUNTINGTON CHOREA; IMMUNE RESPONSE; MALE; MIDDLE AGED; NERVOUS SYSTEM INFLAMMATION; NEUROPATHOLOGY; NEXT GENERATION SEQUENCING; PREFRONTAL CORTEX; RNA SEQUENCE; SCORING SYSTEM; SEQUENCE ANALYSIS; TRANSCRIPTION REGULATION; UPREGULATION; AGED; BRAIN; DEVELOPMENTAL GENE; GENE EXPRESSION PROFILING; GENETICS; IMMUNOLOGY; INFLAMMATION; METABOLISM; PROCEDURES;

ADULT; AGED; BRAIN; GENE EXPRESSION PROFILING; GENE EXPRESSION REGULATION; GENES, DEVELOPMENTAL; GENES, HOMEOBOX; HUMANS; HUNTINGTON DISEASE; INFLAMMATION; MALE; MIDDLE AGED; SEQUENCE ANALYSIS, RNA;

EID: 84957109105     PISSN: None     EISSN: 19326203     Source Type: Journal    
DOI: 10.1371/journal.pone.0143563     Document Type: Article

References (67)

1. Huntington G. On chorea. Med Surg Rep. 1872; 26: 317-321.
2. Myers R, Marans K, MacDonald M. Huntington's Disease. Genetic Instabilities and Hereditary Neurological Diseases. Academic Press; 1998. pp. 301-323.
3. MacDonald ME, Ambrose CM, Duyao MP, Myers RH, Lin C, Srinidhi L, et al. A novel gene containing a trinucleotide repeat that is expanded and unstable on Huntington's disease chromosomes. Cell. 1993; 72: 971-983. doi: 10.1016/0092-8674(93)90585-E PMID: 8458085
4. Vonsattel JP, Myers RH, Stevens TJ, Ferrante RJ, Bird ED, Richardson EPJ. Neuropathological classification of Huntington's disease. J Neuropathol Exp Neurol. 1985; 44: 559-577. PMID: 2932539
5. Myers RH. Huntington's disease genetics. NeuroRx J Am Soc Exp Neurother. 2004; 1: 255-262. doi: 10.1602/neurorx.1.2.255
6. Cha J-HJ. Transcriptional dysregulation in Huntington's disease. Trends Neurosci. 2000; 23: 387-392. doi: 10.1016/S0166-2236(00)01609-X PMID: 10941183
7. Cha J-HJ. Transcriptional Signatures in Huntington's Disease. Prog Neurobiol. 2007; 83: 228-248. doi: 10.1016/j.pneurobio.2007.03.004 PMID: 17467140
8. Sotrel A, Paskevich PA, Kiely DK, Bird ED, Williams RS, Myers RH. Morphometric analysis of the prefrontal cortex in Huntington's disease. Neurology. 1991; 41: 1117-1117. doi: 10.1212/WNL.41.7.1117 PMID: 1829794
9. Sotrel A, Williams RS, Kaufmann WE, Myers RH. Evidence for neuronal degeneration and dendritic plasticity in cortical pyramidal neurons of Huntington's disease: a quantitative Golgi study. Neurology. 1993; 43: 2088-2096. PMID: 8413971
10. Hoss AG, Kartha VK, Dong X, Latourelle JC, Dumitriu A, Hadzi TC, et al. MicroRNAs Located in the Hox Gene Clusters Are Implicated in Huntington's Disease Pathogenesis. PLoS Genet. 2014; 10: e1004188. doi: 10.1371/journal.pgen.1004188 PMID: 24586208
11. Hadzi TC, Hendricks AE, Latourelle JC, Lunetta KL, Cupples LA, Gillis T, et al. Assessment of cortical and striatal involvement in 523 Huntington disease brains. Neurology. 2012; 79: 1708-1715. doi: 10. 1212/WNL.0b013e31826e9a5d PMID: 23035064
12. Harrow J, Frankish A, Gonzalez JM, Tapanari E, Diekhans M, Kokocinski F, et al. GENCODE: The reference human genome annotation for The ENCODE Project. Genome Res. 2012; 22: 1760-1774. doi: 10.1101/gr.135350.111 PMID: 22955987
13. Huang DW, Sherman BT, Lempicki RA. Systematic and integrative analysis of large gene lists using DAVID bioinformatics resources. Nat Protoc. 2008; 4: 44-57. doi: 10.1038/nprot.2008.211
14. Huang DW, Sherman BT, Lempicki RA. Bioinformatics enrichment tools: paths toward the comprehensive functional analysis of large gene lists. Nucleic Acids Res. 2009; 37: 1-13. doi: 10.1093/nar/gkn923 PMID: 19033363
15. Ashburner M, Ball CA, Blake JA, Botstein D, Butler H, Cherry JM, et al. Gene Ontology: tool for the unification of biology. Nat Genet. 2000; 25: 25-29. doi: 10.1038/75556 PMID: 10802651
16. Subramanian A, Tamayo P, Mootha VK, Mukherjee S, Ebert BL, Gillette MA, et al. Gene set enrichment analysis: A knowledge-based approach for interpreting genome-wide expression profiles. Proc Natl Acad Sci U S A. 2005; 102: 15545-15550. doi: 10.1073/pnas.0506580102 PMID: 16199517
17. Alexa A, Rahnenfuhrer J. topGO: Enrichment analysis for Gene Ontology. 2014.
18. Croft D, Mundo AF, Haw R, Milacic M, Weiser J, Wu G, et al. The Reactome pathway knowledgebase. Nucleic Acids Res. 2014; 42: D472-D477. doi: 10.1093/nar/gkt1102 PMID: 24243840
19. Milacic M, Haw R, Rothfels K, Wu G, Croft D, Hermjakob H, et al. Annotating Cancer Variants and Anti-Cancer Therapeutics in Reactome. Cancers. 2012; 4: 1180-1211. doi: 10.3390/cancers4041180 PMID: 24213504
20. Kanehisa M, Goto S. KEGG: Kyoto Encyclopedia of Genes and Genomes. Nucleic Acids Res. 2000; 28: 27-30. PMID: 10592173
21. Schaefer CF, Anthony K, Krupa S, Buchoff J, Day M, Hannay T, et al. PID: the Pathway Interaction Database. Nucleic Acids Res. 2009; 37: D674-D679. doi: 10.1093/nar/gkn653 PMID: 18832364
22. Li S-H, Cheng AL, Zhou H, Lam S, Rao M, Li H, et al. Interaction of Huntington Disease Protein with Transcriptional Activator Sp1. Mol Cell Biol. 2002; 22: 1277-1287. PMID: 11839795
23. van Roon-Mom WMC, Reid SJ, Jones AL, MacDonald ME, Faull RLM, Snell RG. Insoluble TATA-binding protein accumulation in Huntington's disease cortex. Brain Res Mol Brain Res. 2002; 109: 1-10. PMID: 12531510
24. O'Neill LAJ, Kaltschmidt C. NF-kB: a crucial transcription factor for glial and neuronal cell function. Trends Neurosci. 1997; 20: 252-258. doi: 10.1016/S0166-2236(96)01035-1 PMID: 9185306
25. Meffert MK, Chang JM, Wiltgen BJ, Fanselow MS, Baltimore D. NF-κB functions in synaptic signaling and behavior. Nat Neurosci. 2003; 6: 1072-1078. doi: 10.1038/nn1110 PMID: 12947408
26. Marcora E, Kennedy MB. The Huntington's disease mutation impairs Huntingtin's role in the transport of NF-?B from the synapse to the nucleus. Hum Mol Genet. 2010; 19: 4373-4384. doi: 10.1093/hmg/ddq358 PMID: 20739295
27. Hayashida N, Fujimoto M, Tan K, Prakasam R, Shinkawa T, Li L, et al. Heat shock factor 1 ameliorates proteotoxicity in cooperation with the transcription factor NFAT. EMBO J. 2010; 29: 3459-3469. doi: 10. 1038/emboj.2010.225 PMID: 20834230
28. Neef DW, Turski ML, Thiele DJ. Modulation of Heat Shock Transcription Factor 1 as a Therapeutic Target for Small Molecule Intervention in Neurodegenerative Disease. PLoS Biol. 2010; 8: e1000291. doi: 10.1371/journal.pbio.1000291 PMID: 20098725
29. Crotti A, Benner C, Kerman BE, Gosselin D, Lagier-Tourenne C, Zuccato C, et al. Mutant Huntingtin promotes autonomous microglia activation via myeloid lineage-determining factors. Nat Neurosci. 2014; 17: 513-521. doi: 10.1038/nn.3668 PMID: 24584051
30. Djousse L, Knowlton B, Hayden MR, Almqvist EW, Brinkman RR, Ross CA, et al. Evidence for a modifier of onset age in Huntington disease linked to the HD gene in 4p16. Neurogenetics. 2004; 5: 109-114. doi: 10.1007/s10048-004-0175-2 PMID: 15029481
31. Baumann N, Pham-Dinh D. Biology of Oligodendrocyte and Myelin in the Mammalian Central Nervous System. Physiol Rev. 2001; 81: 871-927. PMID: 11274346
32. D'Aversa TG, Eugenin EA, Lopez L, Berman JW. Myelin Basic Protein Induces Inflammatory Mediators From Primary Human Endothelial Cells and Blood-Brain-Barrier Disruption: Implications for the Pathogenesis of Multiple Sclerosis. Neuropathol Appl Neurobiol. 2013; 39: 270-283. doi: 10.1111/j.1365-2990.2012.01279.x PMID: 22524708
33. Lumpkins KM, Bochicchio GV, Keledjian K, Simard JM, McCunn M, Scalea T. Glial Fibrillary Acidic Protein is Highly Correlated With Brain Injury. J Trauma-Inj Infect. 2008; 65: 778-784. doi: 10.1097/TA. 0b013e318185db2d
34. Jones SE, Jomary C. Clusterin. Int J Biochem Cell Biol. 2002; 34: 427-431. PMID: 11906815
35. Suárez I, Bodega G, Fernández B. Glutamine synthetase in brain: effect of ammonia. Neurochem Int. 2002; 41: 123-142. doi: 10.1016/S0197-0186(02)00033-5 PMID: 12020613
36. Blumkin L, Halevy A, Ben-Ami-Raichman D, Dahari D, Haviv A, Sarit C, et al. Expansion of the spectrum of TUBB4A-related disorders: a new phenotype associated with a novel mutation in the TUBB4A gene. neurogenetics. 2014; 15: 107-113. doi: 10.1007/s10048-014-0392-2 PMID: 24526230
37. Thrane AS, Rappold PM, Fujita T, Torres A, Bekar LK, Takano T, et al. Critical role of aquaporin-4 (AQP4) in astrocytic Ca2+ signaling events elicited by cerebral edema. Proc Natl Acad Sci U S A. 2011; 108: 846-851. doi: 10.1073/pnas.1015217108 PMID: 21187412
38. Cronberg T, Rundgren M, Westhall E, Englund E, Siemund R, Rosén I, et al. Neuron-specific enolase correlates with other prognostic markers after cardiac arrest. Neurology. 2011; 77: 623-630. doi: 10. 1212/WNL.0b013e31822a276d PMID: 21775743
39. Ponomarev ED, Shriver LP, Dittel BN. CD40 Expression by Microglial Cells Is Required for Their Completion of a Two-Step Activation Process during Central Nervous System Autoimmune Inflammation. J Immunol. 2006; 176: 1402-1410. doi: 10.4049/jimmunol.176.3.1402 PMID: 16424167
40. Jackson BC, Carpenter C, Nebert DW, Vasiliou V. Update of human and mouse forkhead box (FOX) gene families. Hum Genomics. 2010; 4: 345. doi: 10.1186/1479-7364-4-5-345 PMID: 20650821
41. Ellrichmann G, Reick C, Saft C, Linker RA. The Role of the Immune System in Huntington's Disease. J Immunol Res. 2013; 2013: e541259. doi: 10.1155/2013/541259
42. Silvestroni A, Faull RLM, Strand AD, Moller TA. Distinct neuroinflammatory profile in post-mortem human Huntington's disease. [Miscellaneous Article]. Neuroreport August 5 2009. 2009; 20: 1098-1103. doi: 10.1097/WNR.0b013e32832e34ee PMID: 19590393
43. Björkqvist M, Wild EJ, Thiele J, Silvestroni A, Andre R, Lahiri N, et al. A novel pathogenic pathway of immune activation detectable before clinical onset in Huntington's disease. J Exp Med. 2008; 205: 1869-1877. doi: 10.1084/jem.20080178 PMID: 18625748
44. Gafni J, Ellerby LM. Calpain Activation in Huntington's Disease. J Neurosci. 2002; 22: 4842-4849. PMID: 12077181
45. Gafni J, Hermel E, Young JE, Wellington CL, Hayden MR, Ellerby LM. Inhibition of Calpain Cleavage of Huntingtin Reduces Toxicity ACCUMULATION OF CALPAIN/CASPASE FRAGMENTS IN THE NUCLEUS. J Biol Chem. 2004; 279: 20211-20220. doi: 10.1074/jbc.M401267200 PMID: 14981075
46. Goll DE, Thompson VF, Li H, Wei W, Cong J. The Calpain System. Physiol Rev. 2003; 83: 731-801. doi: 10.1152/physrev.00029.2002 PMID: 12843408
47. Gronski MA, Kinchen JM, Juncadella IJ, Franc NC, Ravichandran KS. An essential role for calcium flux in phagocytes for apoptotic cell engulfment and the anti-inflammatory response. Cell Death Differ. 2009; 16: 1323-1331. doi: 10.1038/cdd.2009.55 PMID: 19461656
48. Razzell W, Evans IR, Martin P, Wood W. Calcium Flashes Orchestrate the Wound Inflammatory Response through DUOX Activation and Hydrogen Peroxide Release. Curr Biol. 2013; 23: 424-429. doi: 10.1016/j.cub.2013.01.058 PMID: 23394834
49. Giacomello M, Hudec R, Lopreiato R. Huntington's disease, calcium, and mitochondria. BioFactors. 2011; 37: 206-218. doi: 10.1002/biof.162 PMID: 21674644
50. Wojda U, Salinska E, Kuznicki J. Calcium ions in neuronal degeneration. IUBMB Life. 2008; 60: 575-590. doi: 10.1002/iub.91 PMID: 18478527
51. Damiano M, Galvan L, Déglon N, Brouillet E. Mitochondria in Huntington's disease. Biochim Biophys Acta BBA-Mol Basis Dis. 2010; 1802: 52-61. doi: 10.1016/j.bbadis.2009.07.012
52. Costa V, Scorrano L. Shaping the role of mitochondria in the pathogenesis of Huntington's disease. EMBO J. 2012; 31: 1853-1864. doi: 10.1038/emboj.2012.65 PMID: 22446390
53. Schapira AHV, Olanow CW, Greenamyre JT, Bezard E. Slowing of neurodegeneration in Parkinson's disease and Huntington's disease: future therapeutic perspectives. The Lancet. 2014; 384: 545-555. doi: 10.1016/S0140-6736(14)61010-2
54. Hodges A, Strand AD, Aragaki AK, Kuhn A, Sengstag T, Hughes G, et al. Regional and cellular gene expression changes in human Huntington's disease brain. Hum Mol Genet. 2006; 15: 965-977. doi: 10. 1093/hmg/ddl013 PMID: 16467349
55. Selemon LD, Rajkowska G, Goldman-Rakic PS. Evidence for progression in frontal cortical pathology in late-stage Huntington's disease. J Comp Neurol. 2004; 468: 190-204. doi: 10.1002/cne.10938 PMID: 14648679
56. Squitieri F, Cannella M, Simonelli M, Sassone J, Martino T, Venditti E, et al. Distinct Brain Volume Changes Correlating with Clinical Stage, Disease Progression Rate, Mutation Size, and Age at Onset Prediction as Early Biomarkers of Brain Atrophy in Huntington's Disease. CNS Neurosci Ther. 2009; 15: 1-11. doi: 10.1111/j.1755-5949.2008.00068.x PMID: 19228174
57. Hobbs NZ, Barnes J, Frost C, Henley SMD, Wild EJ, Macdonald K, et al. Onset and Progression of Pathologic Atrophy in Huntington Disease: A Longitudinal MR Imaging Study. Am J Neuroradiol. 2010; 31: 1036-1041. doi: 10.3174/ajnr.A2018 PMID: 20150305
58. Seok J, Warren HS, Cuenca AG, Mindrinos MN, Baker HV, Xu W, et al. Genomic responses in mouse models poorly mimic human inflammatory diseases. Proc Natl Acad Sci. 2013; 110: 3507-3512. doi: 10.1073/pnas.1222878110 PMID: 23401516
59. Beach TG, Sue LI, Walker DG, Roher AE, Lue L, Vedders L, et al. The Sun Health Research Institute Brain Donation Program: Description and Eexperience, 1987-2007. Cell Tissue Bank. 2008; 9: 229-245. doi: 10.1007/s10561-008-9067-2 PMID: 18347928
60. Lander ES, Linton LM, Birren B, Nusbaum C, Zody MC, Baldwin J, et al. Initial sequencing and analysis of the human genome. Nature. 2001; 409: 860-921. doi: 10.1038/35057062 PMID: 11237011
61. Kim D, Pertea G, Trapnell C, Pimentel H, Kelley R, Salzberg SL. TopHat2: accurate alignment of transcriptomes in the presence of insertions, deletions and gene fusions. Genome Biol. 2013; 14: R36. doi: 10.1186/gb-2013-14-4-r36 PMID: 23618408
62. Anders S, Pyl PT, Huber W. HTSeq-A Python framework to work with high-throughput sequencing data. bioRxiv. 2014; 002824. doi: 10.1101/002824
63. Love MI, Huber W, Anders S. Moderated estimation of fold change and dispersion for RNA-Seq data with DESeq2. bioRxiv. 2014; 002832. doi: 10.1101/002832
64. R Development Core Team. R: A Language and Environment for Statistical Computing [Internet]. Vienna, Austria: R Foundation for Statistical Computing; 2008. Available: http://www.rproject.org%7D %2C.
65. Hunter JD. Matplotlib: A 2D Graphics Environment. Comput Sci Eng. 2007; 9: 90-95. doi: 10.1109/MCSE.2007.55
66. Pérez F, Granger BE. IPython: A System for Interactive Scientific Computing. Comput Sci Eng. 2007; 9: 21-29. doi: 10.1109/MCSE.2007.53
67. McKinney W. Data Structures for Statistical Computing in Python. Proceedings of the 9th Python in Science Conference. 2010. pp. 51-56.