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Molecular Neurobiology

, Volume 56, Issue 10, pp 7003–7021 | Cite as

Alterations in Striatal microRNA-mRNA Networks Contribute to Neuroinflammation in Multiple System Atrophy

  • Taeyeon Kim
  • Elvira Valera
  • Paula DesplatsEmail author
Article

Abstract

Multiple systems atrophy (MSA) is a rare neurodegenerative disorder characterized by the accumulation of α-synuclein in glial cells and neurodegeneration in the striatum, substantia nigra, and cerebellum. Aberrant miRNA regulation has been associated with neurodegeneration, including alterations of specific miRNAs in brain tissue, serum, and cerebrospinal fluid from MSA patients. Still, a causal link between deregulation of miRNA networks and pathological changes in the transcriptome remains elusive. We profiled ~ 800 miRNAs in the striatum of MSA patients in comparison to healthy individuals to identify specific miRNAs altered in MSA. In addition, we performed a parallel screening of 700 transcripts associated with neurodegeneration to determine the impact of miRNA deregulation on the transcriptome. We identified 60 miRNAs with abnormal levels in MSA brains that are involved in extracellular matrix receptor interactions, prion disease, inflammation, ubiquitin-mediated proteolysis, and addiction pathways. Using the correlation between miRNA expression and the abundance of their known targets, miR-124-3p, miR-19a-3p, miR-27b-3p, and miR-29c-3p were identified as key regulators altered in MSA, mainly contributing to neuroinflammation. Finally, our study also uncovered a potential link between Alzheimer’s disease (AD) and MSA pathologies that involves miRNAs and deregulation of BACE1. Our results provide a comprehensive appraisal of miRNA alterations in MSA and their effect on the striatal transcriptome, supporting that aberrant miRNA expression is highly correlated with changes in gene transcription associated with MSA neuropathology, in particular those driving inflammation, disrupting myelination, and potentially impacting α-synuclein accumulation via deregulation of autophagy and prion mechanisms.

Keywords

Multiple systems atrophy microRNA Alpha-synuclein Neurodegeneration Inflammation Transcription 

Abbreviations

MSA

multiple system atrophy

α-syn

alpha-synuclein

GCIs

glial cytoplasmic inclusions

lincRNAs

long intervening non-coding RNA

miRNAs

microRNA

CSF

cerebrospinal fluid

AD

Alzheimer’s disease

PD

Parkinson’s disease

CT

control cases

ECM

extracellular matrix

DLB

dementia with Lewy bodies

GSEA

gene set enrichment analysis

DE

differentially expressed genes

IPA

ingenuity pathway analysis

APP

amyloid precursor protein

Notes

Acknowledgments

We are grateful to the University of California, San Diego Shiley-Marcos AD Research Center, and the Johns Hopkins Medical Institution Brain Resource Center for the provision of brain tissue. The authors want to thank Dr. Elsa Molina, Director of the Sanford Stem Cell Clinical Center, and UCSD-Sanford Consortium for Regenerative Medicine for technical assistance with array processing.

Funding information

This work was supported by the NIH grant NS092803 from NINDS to P.D. The UCSD Shiley-Marcos Alzheimer’s Disease Research Center is supported by the NIH grant AG05131.

Supplementary material

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References

  1. 1.
    Spillantini MG, Crowther RA, Jakes R, Cairns NJ, Lantos PL, Goedert M (1998) Filamentous alpha-synuclein inclusions link multiple system atrophy with Parkinson’s disease and dementia with Lewy bodies. Neurosci Lett 251(3):205–208Google Scholar
  2. 2.
    Wakabayashi K, Hayashi S, Kakita A, Yamada M, Toyoshima Y, Yoshimoto M, Takahashi H (1998) Accumulation of alpha-synuclein/NACP is a cytopathological feature common to Lewy body disease and multiple system atrophy. Acta Neuropathol 96(5):445–452Google Scholar
  3. 3.
    Wakabayashi K, Yoshimoto M, Tsuji S, Takahashi H (1998) Alpha-synuclein immunoreactivity in glial cytoplasmic inclusions in multiple system atrophy. Neurosci Lett 249(2–3):180–182Google Scholar
  4. 4.
    Gilman S, Wenning GK, Low PA, Brooks DJ, Mathias CJ, Trojanowski JQ, Wood NW, Colosimo C et al (2008) Second consensus statement on the diagnosis of multiple system atrophy. Neurology 71(9):670–676Google Scholar
  5. 5.
    Miki Y, Tanji K, Mori F, Utsumi J, Sasaki H, Kakita A, Takahashi H, Wakabayashi K (2016) Alteration of upstream autophagy-related proteins (ULK1, ULK2, Beclin1, VPS34 and AMBRA1) in Lewy body disease. Brain Pathol 26(3):359–370Google Scholar
  6. 6.
    Schwarz L, Goldbaum O, Bergmann M, Probst-Cousin S, Richter-Landsberg C (2012) Involvement of macroautophagy in multiple system atrophy and protein aggregate formation in oligodendrocytes. J Mol Neurosci 47(2):256–266Google Scholar
  7. 7.
    Vijayakumaran S, Wong MB, Antony H, Pountney DL (2015) Direct and/or indirect roles for SUMO in modulating alpha-synuclein toxicity. Biomolecules 5(3):1697–1716Google Scholar
  8. 8.
    Winslow AR, Rubinsztein DC (2011) The Parkinson disease protein alpha-synuclein inhibits autophagy. Autophagy 7(4):429–431Google Scholar
  9. 9.
    Kaji S, Maki T, Kinoshita H, Uemura N, Ayaki T, Kawamoto Y, Furuta T, Urushitani M et al (2018) Pathological endogenous alpha-synuclein accumulation in oligodendrocyte precursor cells potentially induces inclusions in multiple system atrophy. Stem Cell Rep 10(2):356–365Google Scholar
  10. 10.
    Konno M, Hasegawa T, Baba T, Miura E, Sugeno N, Kikuchi A, Fiesel FC, Sasaki T et al (2012) Suppression of dynamin GTPase decreases alpha-synuclein uptake by neuronal and oligodendroglial cells: a potent therapeutic target for synucleinopathy. Mol Neurodegener 7:38Google Scholar
  11. 11.
    Woerman AL, Watts JC, Aoyagi A, Giles K, Middleton LT, Prusiner SB (2018) Alpha-synuclein: multiple system atrophy prions. Cold Spring Harb Perspect Med. Cold Spring Harb Perspect Med 2;8Google Scholar
  12. 12.
    Chen J, Mills JD, Halliday GM, Janitz M (2015) Role of transcriptional control in multiple system atrophy. Neurobiol Aging 36(1):394–400Google Scholar
  13. 13.
    Langerveld AJ, Mihalko D, DeLong C, Walburn J, Ide CF (2007) Gene expression changes in postmortem tissue from the rostral pons of multiple system atrophy patients. Mov Disord 22(6):766–777Google Scholar
  14. 14.
    Mills JD, Ward M, Kim WS, Halliday GM, Janitz M (2016) Strand-specific RNA-sequencing analysis of multiple system atrophy brain transcriptome. Neuroscience 322:234–250Google Scholar
  15. 15.
    Lee ST, Chu K, Jung KH, Ban JJ, Im WS, Jo HY, Park JH, Lim JY et al (2015) Altered expression of miR-202 in cerebellum of multiple-system atrophy. Mol Neurobiol 51(1):180–186Google Scholar
  16. 16.
    Schafferer S, Khurana R, Refolo V, Venezia S, Sturm E, Piatti P, Hechenberger C, Hackl H et al (2016) Changes in the miRNA-mRNA regulatory network precede motor symptoms in a mouse model of multiple system atrophy: clinical implications. PLoS One 11(3):e0150705Google Scholar
  17. 17.
    Ubhi K, Rockenstein E, Kragh C, Inglis C, Spencer B, Michael S, Mante M, Adame A et al (2014) Widespread microRNA dysregulation in multiple system atrophy - disease-related alteration in miR-96. Eur J Neurosci 39(6):1026–1041Google Scholar
  18. 18.
    Valera E, Spencer B, Mott J, Trejo M, Adame A, Mante M, Rockenstein E, Troncoso JC et al (2017) MicroRNA-101 modulates autophagy and oligodendroglial alpha-synuclein accumulation in multiple system atrophy. Front Mol Neurosci 10:329Google Scholar
  19. 19.
    Vallelunga A, Ragusa M, Di Mauro S, Iannitti T, Pilleri M, Biundo R, Weis L, Di Pietro C et al (2014) Identification of circulating microRNAs for the differential diagnosis of Parkinson’s disease and multiple system atrophy. Front Cell Neurosci 8:156Google Scholar
  20. 20.
    Kume K, Iwama H, Deguchi K, Ikeda K, Takata T, Kokudo Y, Kamada M, Fujikawa K et al (2018) Serum microRNA expression profiling in patients with multiple system atrophy. Mol Med Rep 17(1):852–860Google Scholar
  21. 21.
    Marques TM, Kuiperij HB, Bruinsma IB, van Rumund A, Aerts MB, Esselink RAJ, Bloem BR, Verbeek MM (2017) MicroRNAs in cerebrospinal fluid as potential biomarkers for Parkinson’s disease and multiple system atrophy. Mol Neurobiol 54(10):7736–7745Google Scholar
  22. 22.
    Swarts DC, Makarova K, Wang Y, Nakanishi K, Ketting RF, Koonin EV, Patel DJ, van der Oost J (2014) The evolutionary journey of Argonaute proteins. Nat Struct Mol Biol 21(9):743–753Google Scholar
  23. 23.
    Wang W, Kwon EJ, Tsai LH (2012) MicroRNAs in learning, memory, and neurological diseases. Learn Mem 19(9):359–368Google Scholar
  24. 24.
    Zhao X, He X, Han X, Yu Y, Ye F, Chen Y, Hoang T, Xu X et al (2010) MicroRNA-mediated control of oligodendrocyte differentiation. Neuron 65(5):612–626Google Scholar
  25. 25.
    Patrick E, Rajagopal S, Wong H-K, McCabe C, Xu J, Tang A, Imboywa SH, Schneider JA et al (2017) Dissecting the role of non-coding RNAs in the accumulation of amyloid and tau neuropathologies in Alzheimer’s disease. Mol Neurodegener 12(1):51Google Scholar
  26. 26.
    Schulz J, Takousis P, Wohlers I, Itua I, Dobricic V, Binder H, Middleton L, Ioannidis J et al (2018) Systematic meta-analyses identify differentially expressed microRNAs in Parkinson’s disease.  https://doi.org/10.1101/253849
  27. 27.
    Jin J, Cheng Y, Zhang Y, Wood W, Peng Q, Hutchison E, Mattson MP, Becker KG et al (2012) Interrogation of brain miRNA and mRNA expression profiles reveals a molecular regulatory network that is perturbed by mutant huntingtin. J Neurochem 123(4):477–490Google Scholar
  28. 28.
    Jellinger KA (2014) Neuropathology of multiple system atrophy: new thoughts about pathogenesis. Mov Disord 29(14):1720–1741Google Scholar
  29. 29.
    Peltier HJ, Latham GJ (2008) Normalization of microRNA expression levels in quantitative RT-PCR assays: identification of suitable reference RNA targets in normal and cancerous human solid tissues. RNA 14(5):844–852Google Scholar
  30. 30.
    Ogasawara R, Akimoto T, Umeno T, Sawada S, Hamaoka T, Fujita S (2016) MicroRNA expression profiling in skeletal muscle reveals different regulatory patterns in high and low responders to resistance training. Physiol Genomics 48(4):320–324Google Scholar
  31. 31.
    Vlachos IS, Zagganas K, Paraskevopoulou MD, Georgakilas G, Karagkouni D, Vergoulis T, Dalamagas T, Hatzigeorgiou AG (2015) DIANA-miRPath v3.0: deciphering microRNA function with experimental support. Nucleic Acids Res 43(W1):W460–W466Google Scholar
  32. 32.
    Hosack DA, Dennis G Jr, Sherman BT, Lane HC, Lempicki RA (2003) Identifying biological themes within lists of genes with EASE. Genome Biol 4(10):R70Google Scholar
  33. 33.
    Braak H, Del Tredici K, Rub U, de Vos RA, Jansen Steur EN, Braak E (2003) Staging of brain pathology related to sporadic Parkinson’s disease. Neurobiol Aging 24(2):197–211Google Scholar
  34. 34.
    Agarwal V, Bell GW, Nam JW, Bartel DP (2015) Predicting effective microRNA target sites in mammalian mRNAs. Elife. 2015 12:4.  https://doi.org/10.7554/eLife.05005
  35. 35.
    Wu X, Reddy DS (2012) Integrins as receptor targets for neurological disorders. Pharmacol Ther 134(1):68–81Google Scholar
  36. 36.
    Tsuboi K, Grzesiak JJ, Bouvet M, Hashimoto M, Masliah E, Shults CW (2005) Alpha-synuclein overexpression in oligodendrocytic cells results in impaired adhesion to fibronectin and cell death. Mol Cell Neurosci 29(2):259–268Google Scholar
  37. 37.
    Miners JS, Renfrew R, Swirski M, Love S (2014) Accumulation of alpha-synuclein in dementia with Lewy bodies is associated with decline in the alpha-synuclein-degrading enzymes kallikrein-6 and calpain-1. Acta Neuropathol Commun 2:164Google Scholar
  38. 38.
    Tomfohr J, Lu J, Kepler TB (2005) Pathway level analysis of gene expression using singular value decomposition. BMC Bioinf 6:225Google Scholar
  39. 39.
    Ray A, Shakya A, Kumar D, Benson MD, Ray BK (2006) Inflammation-responsive transcription factor SAF-1 activity is linked to the development of amyloid A amyloidosis. J Immunol 177(4):2601–2609Google Scholar
  40. 40.
    Mukherjee A, Soto C (2011) Role of calcineurin in neurodegeneration produced by misfolded proteins and endoplasmic reticulum stress. Curr Opin Cell Biol 23(2):223–230Google Scholar
  41. 41.
    Bisognin A, Sales G, Coppe A, Bortoluzzi S, Romualdi C (2012) MAGIA(2): from miRNA and genes expression data integrative analysis to microRNA-transcription factor mixed regulatory circuits (2012 update). Nucleic Acids Res 40(Web Server issue):W13–W21Google Scholar
  42. 42.
    Roush S, Slack FJ (2008) The let-7 family of microRNAs. Trends Cell Biol 18(10):505–516Google Scholar
  43. 43.
    Lagos-Quintana M, Rauhut R, Yalcin A, Meyer J, Lendeckel W, Tuschl T (2002) Identification of tissue-specific microRNAs from mouse. Curr Biol 12(9):735–739Google Scholar
  44. 44.
    Ham O, Lee SY, Lee CY, Park JH, Lee J, Seo HH, Cha MJ, Choi E et al (2015) Let-7b suppresses apoptosis and autophagy of human mesenchymal stem cells transplanted into ischemia/reperfusion injured heart 7by targeting caspase-3. Stem Cell Res Ther 6:147Google Scholar
  45. 45.
    Lehmann SM, Kruger C, Park B, Derkow K, Rosenberger K, Baumgart J, Trimbuch T, Eom G et al (2012) An unconventional role for miRNA: let-7 activates toll-like receptor 7 and causes neurodegeneration. Nat Neurosci 15(6):827–835Google Scholar
  46. 46.
    Lalive PH, Benkhoucha M, Tran NL, Kreutzfeldt M, Merkler D, Santiago-Raber ML (2014) TLR7 signaling exacerbates CNS autoimmunity through downregulation of Foxp3+ Treg cells. Eur J Immunol 44(1):46–57Google Scholar
  47. 47.
    Beraud D, Twomey M, Bloom B, Mittereder A, Ton V, Neitzke K, Chasovskikh S, Mhyre TR et al (2011) Alpha-synuclein alters toll-like receptor expression. Front Neurosci 5:80Google Scholar
  48. 48.
    Kim C, Ho DH, Suk JE, You S, Michael S, Kang J, Joong Lee S, Masliah E et al (2013) Neuron-released oligomeric alpha-synuclein is an endogenous agonist of TLR2 for paracrine activation of microglia. Nat Commun 4:1562Google Scholar
  49. 49.
    Frost RJ, Olson EN (2011) Control of glucose homeostasis and insulin sensitivity by the let-7 family of microRNAs. Proc Natl Acad Sci U S A 108(52):21075–21080Google Scholar
  50. 50.
    Bassil F, Canron MH, Vital A, Bezard E, Li Y, Greig NH, Gulyani S, Kapogiannis D et al (2017) Insulin resistance and exendin-4 treatment for multiple system atrophy. Brain 140(5):1420–1436Google Scholar
  51. 51.
    Hebert SS, De Strooper B (2009) Alterations of the microRNA network cause neurodegenerative disease. Trends Neurosci 32(4):199–206Google Scholar
  52. 52.
    Schonrock N, Matamales M, Ittner LM, Gotz J (2012) MicroRNA networks surrounding APP and amyloid-beta metabolism--implications for Alzheimer’s disease. Exp Neurol 235(2):447–454Google Scholar
  53. 53.
    Li W, Jiang Y, Wang Y, Yang S, Bi X, Pan X, Ma A, Li W (2018) MiR-181b regulates autophagy in a model of Parkinson’s disease by targeting the PTEN/Akt/mTOR signaling pathway. Neurosci Lett 675:83–88Google Scholar
  54. 54.
    Hutchison ER, Kawamoto EM, Taub DD, Lal A, Abdelmohsen K, Zhang Y, Wood WH 3rd, Lehrmann E et al (2013) Evidence for miR-181 involvement in neuroinflammatory responses of astrocytes. Glia 61(7):1018–1028Google Scholar
  55. 55.
    Urrea L, Segura-Feliu M, Masuda-Suzukake M, Hervera A, Pedraz L, Garcia Aznar JM, Vila M, Samitier J et al (2018) Involvement of cellular prion protein in alpha-synuclein transport in neurons. Mol Neurobiol 55(3):1847–1860Google Scholar
  56. 56.
    Aulic S, Masperone L, Narkiewicz J, Isopi E, Bistaffa E, Ambrosetti E, Pastore B, De Cecco E et al (2017) Alpha-synuclein amyloids hijack prion protein to gain cell entry, facilitate cell-to-cell spreading and block prion replication. Sci Rep 7(1):10050Google Scholar
  57. 57.
    Calella AM, Farinelli M, Nuvolone M, Mirante O, Moos R, Falsig J, Mansuy IM, Aguzzi A (2010) Prion protein and Abeta-related synaptic toxicity impairment. EMBO Mol Med 2(8):306–314Google Scholar
  58. 58.
    Haas LT, Salazar SV, Kostylev MA, Um JW, Kaufman AC, Strittmatter SM (2016) Metabotropic glutamate receptor 5 couples cellular prion protein to intracellular signalling in Alzheimer’s disease. Brain 139(Pt 2):526–546Google Scholar
  59. 59.
    Kostylev MA, Kaufman AC, Nygaard HB, Patel P, Haas LT, Gunther EC, Vortmeyer A, Strittmatter SM (2015) Prion-protein-interacting amyloid-beta oligomers of high molecular weight are tightly correlated with memory impairment in multiple Alzheimer mouse models. J Biol Chem 290(28):17415–17438Google Scholar
  60. 60.
    Bellingham SA, Coleman BM, Hill AF (2012) Small RNA deep sequencing reveals a distinct miRNA signature released in exosomes from prion-infected neuronal cells. Nucleic Acids Res 40(21):10937–10949Google Scholar
  61. 61.
    Lobo MK, Nestler EJ (2011) The striatal balancing act in drug addiction: distinct roles of direct and indirect pathway medium spiny neurons. Front Neuroanat 5:41Google Scholar
  62. 62.
    Caplan IF, Maguire-Zeiss KA (2018) Toll-like receptor 2 signaling and current approaches for therapeutic modulation in synucleinopathies. Front Pharmacol 9:417Google Scholar
  63. 63.
    Joshi N, Singh S (2018) Updates on immunity and inflammation in Parkinson disease pathology. J Neurosci Res 96(3):379–390Google Scholar
  64. 64.
    Crews L, Spencer B, Desplats P, Patrick C, Paulino A, Rockenstein E, Hansen L, Adame A et al (2010) Selective molecular alterations in the autophagy pathway in patients with Lewy body disease and in models of alpha-synucleinopathy. PLoS One 5(2):e9313Google Scholar
  65. 65.
    Wong E, Cuervo AM (2010) Autophagy gone awry in neurodegenerative diseases. Nat Neurosci 13(7):805–811Google Scholar
  66. 66.
    Mitsui J, Matsukawa T, Sasaki H, Yabe I, Matsushima M, Durr A, Brice A, Takashima H et al (2015) Variants associated with Gaucher disease in multiple system atrophy. Ann Clin Transl Neurol 2(4):417–426Google Scholar
  67. 67.
    Sklerov M, Kang UJ, Liong C, Clark L, Marder K, Pauciulo M, Nichols WC, Chung WK et al (2017) Frequency of GBA variants in autopsy-proven multiple system atrophy. Mov Disord Clin Pract 4(4):574–581Google Scholar
  68. 68.
    Bando Y, Hagiwara Y, Suzuki Y, Yoshida K, Aburakawa Y, Kimura T, Murakami C, Ono M et al (2018) Kallikrein 6 secreted by oligodendrocytes regulates the progression of experimental autoimmune encephalomyelitis. Glia 66(2):359–378Google Scholar
  69. 69.
    Duncan GJ, Plemel JR, Assinck P, Manesh SB, Muir FGW, Hirata R, Berson M, Liu J et al (2017) Myelin regulatory factor drives remyelination in multiple sclerosis. Acta Neuropathol 134(3):403–422Google Scholar
  70. 70.
    Meixner M, Jungnickel J, Grothe C, Gieselmann V, Eckhardt M (2011) Myelination in the absence of UDP-galactose: ceramide galactosyl-transferase and fatty acid 2 -hydroxylase. BMC Neurosci 12:22Google Scholar
  71. 71.
    Southwood C, He C, Garbern J, Kamholz J, Arroyo E, Gow A (2004) CNS myelin paranodes require Nkx6-2 homeoprotein transcriptional activity for normal structure. J Neurosci 24(50):11215–11225Google Scholar
  72. 72.
    Vijay S, Chiu M, Dacks JB, Roberts RC (2016) Exclusive expression of the Rab11 effector SH3TC2 in Schwann cells links integrin-alpha6 and myelin maintenance to Charcot-Marie-tooth disease type 4C. Biochim Biophys Acta 1862(7):1279–1290Google Scholar
  73. 73.
    Peters F, Salihoglu H, Rodrigues E, Herzog E, Blume T, Filser S, Dorostkar M, Shimshek DR et al (2018) BACE1 inhibition more effectively suppresses initiation than progression of beta-amyloid pathology. Acta Neuropathol 135(5):695–710Google Scholar
  74. 74.
    Bujan B, Hofer MJ, Oertel WH, Pagenstecher A, Burk K (2013) Multiple system atrophy of the cerebellar type (MSA-C) with concomitant beta-amyloid and tau pathology. Clin Neuropathol 32(4):286–290Google Scholar
  75. 75.
    Ponomarev ED, Veremeyko T, Barteneva N, Krichevsky AM, Weiner HL (2011) MicroRNA-124 promotes microglia quiescence and suppresses EAE by deactivating macrophages via the C/EBP-alpha-PU.1 pathway. Nat Med 17(1):64–70Google Scholar
  76. 76.
    Hamzei Taj S, Kho W, Aswendt M, Collmann FM, Green C, Adamczak J, Tennstaedt A, Hoehn M (2016) Dynamic modulation of microglia/macrophage polarization by miR-124 after focal cerebral ischemia. J NeuroImmune Pharmacol 11(4):733–748Google Scholar
  77. 77.
    Wang H, Ye Y, Zhu Z, Mo L, Lin C, Wang Q, Wang H, Gong X et al (2016) MiR-124 regulates apoptosis and autophagy process in MPTP model of Parkinson’s disease by targeting to Bim. Brain Pathol 26(2):167–176Google Scholar
  78. 78.
    Sonntag KC, Woo TU, Krichevsky AM (2012) Converging miRNA functions in diverse brain disorders: a case for miR-124 and miR-126. Exp Neurol 235(2):427–435Google Scholar
  79. 79.
    Wakabayashi K, Mori F, Kakita A, Takahashi H, Tanaka S, Utsumi J, Sasaki H (2016) MicroRNA expression profiles of multiple system atrophy from formalin-fixed paraffin-embedded samples. Neurosci Lett 635:117–122Google Scholar

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Authors and Affiliations

  1. 1.Department of NeuroscienceUniversity of California San DiegoLa JollaUSA
  2. 2.Department of PathologyUniversity of California San DiegoLa JollaUSA

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