RNA-Seq of Huntington's disease patient myeloid cells reveals innate transcriptional dysregulation associated with proinflammatory pathway activation

Human Molecular Genetics

Volumn 25, Issue 14, 2016, Pages 2893-2904

  Miller, James R C ^a   Lo, Kitty K ^b   Andre, Ralph ^a   Hensman Moss, Davina J ^a   Träger, Ulrike ^a   Stone, Timothy C ^c   Jones, Lesley ^c   Holmans, Peter ^c   Plagnol, Vincent ^b   Tabrizi, Sarah J ^a  

^a UNIVERSITY COLLEGE LONDON   (United Kingdom)

^b UNIVERSITY COLLEGE LONDON   (United Kingdom)

^c CARDIFF UNIVERSITY   (United Kingdom)

Author keywords

[No Author keywords available]

Indexed keywords

BETA ACTIN; CYCLIN DEPENDENT KINASE 2; G PROTEIN COUPLED RECEPTOR; GRANULOCYTE CHEMOTACTIC PROTEIN 2; HUNTINGTIN; IMMUNOGLOBULIN ENHANCER BINDING PROTEIN; INTERLEUKIN 12P40; INTERLEUKIN 19; INTERLEUKIN 1ALPHA; INTERLEUKIN 23P19; INTERLEUKIN 6; MACROPHAGE INFLAMMATORY PROTEIN 3ALPHA; MACROPHAGE INFLAMMATORY PROTEIN 3BETA; MITOGEN ACTIVATED PROTEIN KINASE; MITOGEN ACTIVATED PROTEIN KINASE 1; MITOGEN ACTIVATED PROTEIN KINASE 3; MITOGEN ACTIVATED PROTEIN KINASE P38; MONOCYTE CHEMOTACTIC PROTEIN 2; MYELOID DIFFERENTIATION FACTOR 88; PROSTAGLANDIN SYNTHESIS 2; PROTEIN; STAT3 PROTEIN; TOLL LIKE RECEPTOR 2; TOLL LIKE RECEPTOR 3; TOLL LIKE RECEPTOR 4; TOLL LIKE RECEPTOR 9; TRANSCRIPTION FACTOR RELA; TRANSCRIPTOME; TRANSFORMING GROWTH FACTOR ALPHA; UNCLASSIFIED DRUG; VASCULOTROPIN A; IL6 PROTEIN, HUMAN; NERVE PROTEIN;

ALTERNATIVE RNA SPLICING; ARTICLE; BONE MARROW CELL; CLINICAL ARTICLE; CONTROLLED STUDY; DISEASE COURSE; ENZYME ACTIVATION; GENE EXPRESSION; HUMAN; HUMAN CELL; HUNTINGTON CHOREA; IMMUNE SYSTEM; INNATE IMMUNITY; INTRACELLULAR SIGNALING; MONOCYTE; PERIPHERAL BLOOD MONONUCLEAR CELL; PRIORITY JOURNAL; PROTEIN PHOSPHORYLATION; RNA SEQUENCE; SIGNAL TRANSDUCTION; WESTERN BLOTTING; BIOSYNTHESIS; GENE EXPRESSION PROFILING; GENETICS; HIGH THROUGHPUT SEQUENCING; INFLAMMATION; METABOLISM; PATHOLOGY; TRANSCRIPTION INITIATION; TRINUCLEOTIDE REPEAT;

GENE EXPRESSION PROFILING; HIGH-THROUGHPUT NUCLEOTIDE SEQUENCING; HUMANS; HUNTINGTIN PROTEIN; HUNTINGTON DISEASE; IMMUNITY, INNATE; INFLAMMATION; INTERLEUKIN-6; MYELOID CELLS; NERVE TISSUE PROTEINS; SIGNAL TRANSDUCTION; TRANSCRIPTIONAL ACTIVATION; TRINUCLEOTIDE REPEAT EXPANSION;

EID: 85014011092     PISSN: 09646906     EISSN: 14602083     Source Type: Journal    
DOI: 10.1093/hmg/ddw142     Document Type: Article

References (51)

1. The Huntington's Disease Collaborative Research Group. (1993) A novel gene containing a trinucleotide repeat that is expanded and unstable on Huntington's disease chromosomes. Cell, 72, 971-983.
2. Ross, C.A. and Tabrizi, S.J. (2011) Huntington's disease: from molecular pathogenesis to clinical treatment. Lancet Neurol., 10, 83-98.
3. Li, S.H., Schilling, G., Young, W.S., Li, X.J., Margolis, R.L., Stine, O.C., Wagster, M.V., Abbott, M.H., Franz, M.L. and Ranen, N.G. (1993) Huntington's disease gene (IT15) is widely expressed in human and rat tissues. Neuron, 11, 985-993.
4. van der Burg, J.M., Björkqvist, M. and Brundin, P. (2009) Beyond the brain: widespread pathology in Huntington's disease. Lancet Neurol., 8, 765-774.
5. Tai, Y.F., Pavese, N., Gerhard, A., Tabrizi, S.J., Barker, R.A., Brooks, D.J. and Piccini, P. (2007) Microglial activation in presymptomatic Huntington's disease gene carriers. Brain, 130, 1759-1766.
6. Björkqvist, M., Wild, E.J., Thiele, J., Silvestroni, A., Andre, R., Lahiri, N., Raibon, E., Lee, R.V., Benn, C.L., Soulet, D., et al. (2008) A novel pathogenic pathway of immune activation detectable before clinical onset in Huntington's disease. J. Exp. Med., 205, 1869-1877.
7. Wild, E., Magnusson, A., Lahiri, N., Krus, U., Orth, M., Tabrizi, S.J. and Björkqvist, M. (2011) Abnormal peripheral chemokine profile in Huntington's disease. PLoS Curr., 3, RRN1231.
8. Politis, M., Lahiri, N., Niccolini, F., Su, P., Wu, K., Giannetti, P., Scahill, R.I., Turkheimer, F.E., Tabrizi, S.J. and Piccini, P. (2015) Increased central microglial activation associated with peripheral cytokine levels in premanifest Huntington's disease gene carriers. Neurobiol. Dis., 83, 115-121.
9. Ellrichmann, G., Reick, C., Saft, C. and Linker, R.A. (2013) The role of the immune system in Huntington's disease. Clin. Dev. Immunol., 2013, 541259.
10. Träger, U., Andre, R., Lahiri, N., Magnusson-Lind, A., Weiss, A., Grueninger, S., McKinnon, C., Sirinathsinghji, E., Kahlon, S., Pfister, E.L. et al. (2014) HTT-lowering reverses Huntington's disease immune dysfunction caused by NFjB pathway dysregulation. Brain, 137, 819-833.
11. Kwan, W., Träger, U., Davalos, D., Chou, A., Bouchard, J., Andre, R., Miller, A., Weiss, A., Giorgini, F., Cheah, C. et al. (2012) Mutant huntingtin impairs immune cell migration in Huntington disease. J. Clin. Invest., 122, 4737-4747.
12. Träger, U., Andre, R., Magnusson-Lind, A., Miller, J.R., Connolly, C., Weiss, A., Grueninger, S., Silajdžić, E., Smith, D.L., Leavitt, B.R. et al. (2015) Characterisation of immune cell function in fragment and full-length Huntington's disease mouse models. Neurobiol. Dis., 73, 388-398.
13. Miller, J.R., Träger, U., Andre, R. and Tabrizi, S.J. (2015) Mutant Huntingtin Does Not Affect the Intrinsic Phenotype of Human Huntington's Disease T Lymphocytes. PLoS One, 10, e0141793.
14. Crotti, A., Benner, C., Kerman, B.E., Gosselin, D., Lagier-Tourenne, C., Zuccato, C., Cattaneo, E., Gage, F.H., Cleveland, D.W. and Glass, C.K. (2014) Mutant Huntingtin promotes autonomous microglia activation via myeloid lineagedetermining factors. Nat. Neurosci., 17, 513-521.
15. Weiss, A., Träger, U., Wild, E.J., Grueninger, S., Farmer, R., Landles, C., Scahill, R.I., Lahiri, N., Haider, S., Macdonald, D. et al. (2012) Mutant huntingtin fragmentation in immune cells tracks Huntington's disease progression. J. Clin. Invest., 122, 3731-3736.
16. Bouchard, J., Truong, J., Bouchard, K., Dunkelberger, D., Desrayaud, S., Moussaoui, S., Tabrizi, S.J., Stella, N. and Muchowski, P.J. (2012) Cannabinoid receptor 2 signaling in peripheral immune cells modulates disease onset and severity in mouse models of huntington's disease. J. Neurosci., 32, 18259-18268.
17. Hsiao, H.Y., Chiu, F.L., Chen, C.M., Wu, Y.R., Chen, H.M., Chen, Y.C., Kuo, H.C. and Chern, Y. (2014) Inhibition of soluble tumor necrosis factor is therapeutic in Huntington's disease. Hum. Mol. Genet., 23, 4328-4344.
18. Zwilling, D., Huang, S.Y., Sathyasaikumar, K.V., Notarangelo, F.M., Guidetti, P., Wu, H.Q., Lee, J., Truong, J., Andrews-Zwilling, Y., Hsieh, E.W. et al. (2011) Kynurenine 3-monooxygenase inhibition in blood ameliorates neurodegeneration. Cell, 145, 863-874.
19. Kwan, W., Magnusson, A., Chou, A., Adame, A., Carson, M.J., Kohsaka, S., Masliah, E., Möller, T., Ransohoff, R., Tabrizi, S.J. et al. (2012) Bone marrow transplantation confers modest benefits in mouse models of Huntington's disease. J. Neurosci., 32, 133-142.
20. Hodges, A., Strand, A.D., Aragaki, A.K., Kuhn, A., Sengstag, T., Hughes, G., Elliston, L.A., Hartog, C., Goldstein, D.R., Thu, D. et al. (2006) Regional and cellular gene expression changes in human Huntington's disease brain. Hum. Mol. Genet., 15, 965-977.
21. Borovecki, F., Lovrecic, L., Zhou, J., Jeong, H., Then, F., Rosas, H.D., Hersch, S.M., Hogarth, P., Bouzou, B., Jensen, R.V. et al. (2005) Genome-wide expression profiling of human blood reveals biomarkers for Huntington'sdisease. Proc. Natl. Acad. Sci. USA, 102, 11023-11028.
22. Seredenina, T. and Luthi-Carter, R. (2012) What have we learned from gene expression profiles in Huntington's disease? Neurobiol. Dis., 45, 83-98.
23. Khoshnan, A., Ko, J., Watkin, E.E., Paige, L.A., Reinhart, P.H. and Patterson, P.H. (2004) Activation of the IkappaB kinase complex and nuclear factor-kappaB contributes to mutant huntingtin neurotoxicity. J. Neurosci., 24, 7999-8008.
24. Akira, S. and Takeda, K. (2004) Toll-like receptor signalling. Nat. Rev. Immunol., 4, 499-511.
25. Runne, H., Kuhn, A., Wild, E.J., Pratyaksha, W., Kristiansen, M., Isaacs, J.D., Régulier, E., Delorenzi, M., Tabrizi, S.J. and Luthi-Carter, R. (2007) Analysis of potential transcriptomic biomarkers for Huntington's disease in peripheral blood. Proc. Natl. Acad. Sci. USA, 104, 14424-14429.
26. Mastrokolias, A., Ariyurek, Y., Goeman, J.J., van Duijn, E., Roos, R.A., van der Mast, R.C., van Ommen, G.B., den Dunnen, J.T., 't Hoen, P.A. and van Roon-Mom, W.M. (2015) Huntington's disease biomarker progression profile identified by transcriptome sequencing in peripheral blood. Eur. J. Hum. Genet., 23, 1349-1356.
27. Fernández-Nogales, M., Cabrera, J.R., Santos-Galindo, M., Hoozemans, J.J., Ferrer, I., Rozemuller, A.J., Hernández, F., Avila, J. and Lucas, J.J. (2014) Huntington's disease is a fourrepeat tauopathy with tau nuclear rods. Nat. Med., 20, 881-885.
28. Black, R.A., Rauch, C.T., Kozlosky, C.J., Peschon, J.J., Slack, J.L., Wolfson, M.F., Castner, B.J., Stocking, K.L., Reddy, P., Srinivasan, S. et al. (1997) A metalloproteinase disintegrin that releases tumour-necrosis factor-alpha from cells. Nature, 385, 729-733.
29. Lacy, P. and Stow, J.L. (2011) Cytokine release from innate immune cells: association with diverse membrane trafficking pathways. Blood, 118, 9-18.
30. Gunawardena, S., Her, L.S., Brusch, R.G., Laymon, R.A., Niesman, I.R., Gordesky-Gold, B., Sintasath, L., Bonini, N.M. and Goldstein, L.S. (2003) Disruption of axonal transport by loss of huntingtin or expression of pathogenic polyQ proteins in Drosophila. Neuron, 40, 25-40.
31. Damiano, M., Galvan, L., Déglon, N. and Brouillet, E. (2010) Mitochondria in Huntington's disease. Biochim. Biophys. Acta., 1802, 52-61.
32. Martin, D.D., Ladha, S., Ehrnhoefer, D.E. and Hayden, M.R. (2015) Autophagy in Huntington disease and huntingtin in autophagy. Trends Neurosci., 38, 26-35.
33. Träger, U., Magnusson, A., Lahiri Swales, N., Wild, E., North, J., Lowdell, M. and Björkqvist, M. (2013) JAK/STAT signalling in Huntington's disease immune cells. PLoS Curr., 5.
34. Hoesel, B. and Schmid, J.A. (2013) The complexity of NF-κB signaling in inflammation and cancer. Mol. Cancer, 12, 86.
35. Seok, J., Warren, H.S., Cuenca, A.G., Mindrinos, M.N., Baker, H.V., Xu, W., Richards, D.R., McDonald-Smith, G.P., Gao, H., Hennessy, L. et al. (2013) Genomic responses in mouse models poorly mimic human inflammatory diseases. Proc. Natl. Acad. Sci. USA, 110, 3507-3512.
36. Shoulson, I. (1981) Huntington disease: functional capacities in patients treated with neuroleptic and antidepressant drugs. Neurology, 31, 1333-1335.
37. Zeller, T., Wild, P., Szymczak, S., Rotival, M., Schillert, A., Castagne, R., Maouche, S., Germain, M., Lackner, K., Rossmann, H. et al. (2010) Genetics and beyond-the transcriptome of human monocytes and disease susceptibility. PLoS One, 5, e10693.
38. Aung, H.T., Schroder, K., Himes, S.R., Brion, K., van Zuylen, W., Trieu, A., Suzuki, H., Hayashizaki, Y., Hume, D.A., Sweet, M.J. et al. (2006) LPS regulates proinflammatory gene expression in macrophages by altering histone deacetylase expression. Faseb J., 20, 1315-1327.
39. Yamamoto, M., Yamazaki, S., Uematsu, S., Sato, S., Hemmi, H., Hoshino, K., Kaisho, T., Kuwata, H., Takeuchi, O., Takeshige, K. et al. (2004) Regulation of Toll/IL-1-receptormediated gene expression by the inducible nuclear protein IkappaBzeta. Nature, 430, 218-222.
40. DeLuca, D.S., Levin, J.Z., Sivachenko, A., Fennell, T., Nazaire, M.D., Williams, C., Reich, M., Winckler, W. and Getz, G. (2012) RNA-SeQC: RNA-seq metrics for quality control and process optimization. Bioinformatics, 28, 1530-1532.
41. Kim, D., Pertea, G., Trapnell, C., Pimentel, H., Kelley, R. and Salzberg, S.L. (2013) TopHat2: accurate alignment of transcriptomes in the presence of insertions, deletions and gene fusions. Genome Biol., 14, R36.
42. Love, M.I., Huber, W. and Anders, S. (2014) Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2. Genome Biol., 15, 550.
43. Frazee, A.C., Pertea, G., Jaffe, A.E., Langmead, B., Salzberg, S.L. and Leek, J.T. (2015) Ballgown bridges the gap between transcriptome assembly and expression analysis. Nat. Biotechnol., 33, 243-246.
44. Subramanian, A., Tamayo, P., Mootha, V.K., Mukherjee, S., Ebert, B.L., Gillette, M.A., Paulovich, A., Pomeroy, S.L., Golub, T.R., Lander, E.S. et al. (2005) Gene set enrichment analysis: a knowledge-based approach for interpreting genome-wide expression profiles. Proc. Natl. Acad. Sci. USA, 102, 15545-15550.
45. Harris, M.A., Clark, J., Ireland, A., Lomax, J., Ashburner, M., Foulger, R., Eilbeck, K., Lewis, S., Marshall, B., Mungall, C. et al. (2004) The Gene Ontology (GO) database and informatics resource. Nucleic Acids Res., 32, D258-D261.
46. Kanehisa, M., Goto, S., Sato, Y., Furumichi, M. and Tanabe, M. (2012) KEGG for integration and interpretation of large-scale molecular data sets. Nucleic Acids Res., 40, D1091-D1014.
47. Mi, H., Muruganujan, A. and Thomas, P.D. (2013) PANTHER in 2013: modeling the evolution of gene function, and other gene attributes, in the context of phylogenetic trees. Nucleic Acids Res., 41, D377-D386.
48. Bult, C.J., Eppig, J.T., Kadin, J.A., Richardson, J.E., Blake, J.A. and Group, M.G.D. (2008) The Mouse Genome Database (MGD): mouse biology and model systems. Nucleic Acids Res., 36, D724-D728.
49. Croft, D., Mundo, A.F., Haw, R., Milacic, M., Weiser, J., Wu, G., Caudy, M., Garapati, P., Gillespie, M., Kamdar, M.R. et al. (2014) The Reactome pathway knowledgebase. Nucleic Acids Res., 42, D472-D477.
50. Schaefer, C.F., Anthony, K., Krupa, S., Buchoff, J., Day, M., Hannay, T. and Buetow, K.H. (2009) PID: the Pathway Interaction Database. Nucleic Acids Res., 37, D674-D679.
51. Storey, J.D. and Tibshirani, R. (2003) Statistical significance for genomewide studies. Proc. Natl. Acad. Sci. USA, 100, 9440-9445.