Research progress of single-cell omics in central nervous system immune diseases

doi:10.3969/j.issn.1672-6731.2022.01.002

Abstract

Abstract: Central nervous system immune diseases include multiple sclerosis (MS), neuromyelitis optica spectrum disorders (NMOSDs), myelin oligodendrocyte glycoprotein - IgG associated disorders (MOGAD) and anti - N - methyl - D - aspartate receptor (NMDAR) encephalitis. The pathogenesis of these diseases is complex, and a variety of central nervous system and peripheral cells are involved. Single-cell omics has achieved high -resolution detection of the expression profile at the level of single -cell through a series of sequencing techniques to analyze cell heterogeneity and functional phenotype. This review will summarize the single cell sequencing (SCS) and its applications in the above-mentioned diseases.

Key words: Autoimmune diseases, Central nervous system diseases, Sequence analysis, B-lymphocytes, T-lymphocytes, Monocytes, Macrophages, Microglia, Dendritic cells, Review

摘要： 中枢神经系统免疫性疾病包括多发性硬化、视神经脊髓炎谱系疾病、抗髓鞘少突胶质细胞糖蛋白抗体相关疾病和抗N-甲基-D-天冬氨酸受体脑炎等，发病机制复杂，多种中枢神经系统和外周来源细胞参与其中。单细胞组学通过一系列测序技术实现高分辨检测单个细胞水平表达谱，以解析细胞异质性及其功能表型。本文对单细胞测序技术在常见中枢神经系统免疫性疾病各类型细胞研究中的进展进行综述。

关键词: 自身免疫疾病, 中枢神经系统疾病, 序列分析, B-淋巴细胞, T淋巴细胞, 单核细胞, 巨噬细胞, 小神经胶质细胞, 树突细胞, 综述

LI Zhi-bin, CHENG Xi, QIU Wei. Research progress of single-cell omics in central nervous system immune diseases[J]. Chinese Journal of Contemporary Neurology and Neurosurgery, 2022, 22(1): 8-16.

李志彬, 程希, 邱伟. 中枢神经系统免疫性疾病单细胞组学研究进展[J]. 中国现代神经疾病杂志, 2022, 22(1): 8-16.

/ / Recommend / Download Citations

URL: https://journal11.magtechjournal.com/cjcnn/EN/10.3969/j.issn.1672-6731.2022.01.002

https://journal11.magtechjournal.com/cjcnn/EN/Y2022/V22/I1/8

References

[1] Zou A, Ramanathan S, Dale RC, Brilot F. Single - cell approaches to investigate B cells and antibodies in autoimmune neurological disorders[J]. Cell Mol Immunol, 2021, 18: 294-306.
[2] Hauser SL, Cree BAC. Treatment of multiple sclerosis: a review[J]. Am J Med, 2020, 133: 1380-1390.
[3] Misevic G. Single - cell omics analyses with single molecular detection: challenges and perspectives[J]. J Biomed Res, 2021, 35: 264-276.
[4] Armand EJ, Li J, Xie F, Luo C, Mukamel EA. Single - cell sequencing of brain cell transcriptomes and epigenomes[J]. Neuron, 2021, 109: 11-26.
[5] Prinz M, Jung S, Priller J. Microglia biology: one century of evolving concepts[J]. Cell, 2019, 179: 292-311.
[6] Colonna M, Butovsky O. Microglia function in the central nervous system during health and neurodegeneration[J]. Annu Rev Immunol, 2017, 35: 441-468.
[7] Borst K, Prinz M. Deciphering the heterogeneity of myeloid cells during neuroinflammation in the single - cell era[J]. Brain Pathol, 2020, 30: 1192-1207.
[8] Jordão MJC, Sankowski R, Brendecke SM, Sagar, Locatelli G, Tai YH, Tay TL, Schramm E, Armbruster S, Hagemeyer N, Groß O, Mai D, Çiçek Ö, Falk T, Kerschensteiner M, Grün D, Prinz M. Single - cell profiling identifies myeloid cell subsets with distinct fates during neuroinflammation[J]. Science, 2019, 363: eaat7554.
[9] Mrdjen D, Pavlovic A, Hartmann FJ, Schreiner B, Utz SG, Leung BP, Lelios I, Heppner FL, Kipnis J, Merkler D, Greter M, Becher B. High - dimensional single - cell mapping of central nervous system immune cells reveals distinct myeloid subsets in health, aging, and disease[J]. Immunity, 2018, 48: 380-395.
[10] Ajami B, Samusik N, Wieghofer P, Ho PP, Crotti A, Bjornson Z, Prinz M, Fantl WJ, Nolan GP, Steinman L. Single-cell mass cytometry reveals distinct populations of brain myeloid cells in mouse neuroinflammation and neurodegeneration models[J]. Nat Neurosci, 2018, 21: 541-551.
[11] Masuda T, Sankowski R, Staszewski O, Prinz M. Microglia heterogeneity in the single-cell era[J]. Cell Rep, 2020, 30: 1271-1281.
[12] Esaulova E, Cantoni C, Shchukina I, Zaitsev K, Bucelli RC, Wu GF, Artyomov MN, Cross AH, Edelson BT. Single-cell RNA-seq analysis of human CSF microglia and myeloid cells in neuroinflammation[J]. Neurol Neuroimmunol Neuroinflamm, 2020, 7: e732.
[13] Giladi A, Wagner LK, Li H, Dörr D, Medaglia C, Paul F, Shemer A, Jung S, Yona S, Mack M, Leutz A, Amit I, Mildner A. Cxcl10(+) monocytes define a pathogenic subset in the central nervous system during autoimmune neuroinflammation[J]. Nat Immunol, 2020, 21: 525-534.
[14] Mendiola AS, Ryu JK, Bardehle S, Meyer - Franke A, Ang KK, Wilson C, Baeten KM, Hanspers K, Merlini M, Thomas S, Petersen MA, Williams A, Thomas R, Rafalski VA, Meza - Acevedo R, Tognatta R, Yan Z, Pfaff SJ, Machado MR, Bedard C, Rios Coronado PE, Jiang X, Wang J, Pleiss MA, Green AJ, Zamvil SS, Pico AR, Bruneau BG, Arkin MR, Akassoglou K. Transcriptional profiling and therapeutic targeting of oxidative stress in neuroinflammation[J]. Nat Immunol, 2020, 21: 513 -524.
[15] Mathur V, Burai R, Vest RT, Bonanno LN, Lehallier B, Zardeneta ME, Mistry KN, Do D, Marsh SE, Abud EM, Blurton-Jones M, Li L, Lashuel HA, Wyss - Coray T. Activation of the STING - dependent type Ⅰ interferon response reduces microglial reactivity and neuroinflammation[J]. Neuron, 2017, 96: 1290 -1302.
[16] Wolf Y, Shemer A, Levy - Efrati L, Gross M, Kim JS, Engel A, David E, Chappell - Maor L, Grozovski J, Rotkopf R, Biton I, Eilam - Altstadter R, Jung S. Microglial MHC class Ⅱ is dispensable for experimental autoimmune encephalomyelitis and cuprizone-induced demyelination[J]. Eur J Immunol, 2018, 48: 1308-1318.
[17] Mundt S, Mrdjen D, Utz SG, Greter M, Schreiner B, Becher B. Conventional DCs sample and present myelin antigens in the healthy CNS and allow parenchymal T cell entry to initiate neuroinflammation[J]. Sci Immunol, 2019, 4: eaau8380.
[18] Hammond TR, Dufort C, Dissing - Olesen L, Giera S, Young A, Wysoker A, Walker AJ, Gergits F, Segel M, Nemesh J, Marsh SE, Saunders A, Macosko E, Ginhoux F, Chen J, Franklin RJM, Piao X, McCarroll SA, Stevens B. Single - cell RNA sequencing of microglia throughout the mouse lifespan and in the injured brain reveals complex cell - state changes[J]. Immunity, 2019, 50: 253-271.
[19] Tay TL, Sagar, Dautzenberg J, Grün D, Prinz M. Unique microglia recovery population revealed by single - cell RNAseq following neurodegeneration[J]. Acta Neuropathol Commun, 2018, 6: 87.
[20] Masuda T, Sankowski R, Staszewski O, Böttcher C, Amann L, Sagar, Scheiwe C, Nessler S, Kunz P, van Loo G, Coenen VA, Reinacher PC, Michel A, Sure U, Gold R, Grün D, Priller J, Stadelmann C, Prinz M. Spatial and temporal heterogeneity of mouse and human microglia at single-cell resolution[J]. Nature, 2019, 566: 388-392.
[21] van der Poel M, Ulas T, Mizee MR, Hsiao CC, Miedema SSM, Adelia, Schuurman KG, Helder B, Tas SW, Schultze JL, Hamann J, Huitinga I. Transcriptional profiling of human microglia reveals grey - white matter heterogeneity and multiple sclerosis-associated changes[J]. Nat Commun, 2019, 10: 1139.
[22] Böttcher C, van der Poel M, Fernández - Zapata C, Schlickeiser S, Leman JKH, Hsiao CC, Mizee MR, Adelia, Vincenten MCJ, Kunkel D, Huitinga I, Hamann J, Priller J. Single - cell mass cytometry reveals complex myeloid cell composition in active lesions of progressive multiple sclerosis[J]. Acta Neuropathol Commun, 2020, 8: 136.
[23] Nugent AA, Lin K, van Lengerich B, Lianoglou S, Przybyla L, Davis SS, Llapashtica C, Wang J, Kim DJ, Xia D, Lucas A, Baskaran S, Haddick PCG, Lenser M, Earr TK, Shi J, Dugas JC, Andreone BJ, Logan T, Solanoy HO, Chen H, Srivastava A, Poda SB, Sanchez PE, Watts RJ, Sandmann T, Astarita G, Lewcock JW, Monroe KM, Di Paolo G. TREM2 regulates microglial cholesterol metabolism upon chronic phagocytic challenge[J]. Neuron, 2020, 105: 837-854.
[24] Duan RN, Yang CL, Du T, Liu A, Wang AR, Sun WJ, Li X, Li JX, Yan CZ, Liu QJ. Smek1 deficiency exacerbates experimental autoimmune encephalomyelitis by activating proinflammatory microglia and suppressing the IDO1 - AhR pathway[J]. J Neuroinflammation, 2021, 18: 145.
[25] Schirmer L, Velmeshev D, Holmqvist S, Kaufmann M, Werneburg S, Jung D, Vistnes S, Stockley JH, Young A, Steindel M, Tung B, Goyal N, Bhaduri A, Mayer S, Engler JB, Bayraktar OA, Franklin RJM, Haeussler M, Reynolds R, Schafer DP, Friese MA, Shiow LR, Kriegstein AR, Rowitch DH. Neuronal vulnerability and multilineage diversity in multiple sclerosis[J]. Nature, 2019, 573: 75-82.
[26] Fransen NL, Hsiao CC, van der Poel M, Engelenburg HJ, Verdaasdonk K, Vincenten MCJ, Remmerswaal EBM, Kuhlmann T, Mason MRJ, Hamann J, Smolders J, Huitinga I. Tissue-resident memory T cells invade the brain parenchyma in multiple sclerosis white matter lesions[J]. Brain, 2020, 143: 1714-1730.
[27] Galli E, Hartmann FJ, Schreiner B, Ingelfinger F, Arvaniti E, Diebold M, Mrdjen D, van der Meer F, Krieg C, Nimer FA, Sanderson N, Stadelmann C, Khademi M, Piehl F, Claassen M, Derfuss T, Olsson T, Becher B. GM-CSF and CXCR₄ define a T helper cell signature in multiple sclerosis[J]. Nat Med, 2019, 25: 1290-1300.
[28] Schafflick D, Xu CA, Hartlehnert M, Cole M, Schulte - Mecklenbeck A, Lautwein T, Wolbert J, Heming M, Meuth SG, Kuhlmann T, Gross CC, Wiendl H, Yosef N, Meyer Zu Horste G. Integrated single cell analysis of blood and cerebrospinal fluid leukocytes in multiple sclerosis[J]. Nat Commun, 2020, 11: 247.
[29] Kowarik MC, Astling D, Gasperi C, Wemlinger S, Schumann H, Dzieciatkowska M, Ritchie AM, Hemmer B, Owens GP, Bennett JL. CNS aquaporin -4 -specific B cells connect with multiple B - cell compartments in neuromyelitis optica spectrum disorder[J]. Ann Clin Transl Neurol, 2017, 4: 369-380.
[30] Ramesh A, Schubert RD, Greenfield AL, Dandekar R, Loudermilk R, Sabatino JJ Jr, Koelzer MT, Tran EB, Koshal K, Kim K, Pröbstel AK, Banerji D, Guo CY, Green AJ, Bove RM, DeRisi JL, Gelfand JM, Cree BAC, Zamvil SS, Baranzini SE, Hauser SL, Wilson MR; University of California, San Francisco MS - EPIC Team. A pathogenic and clonally expanded B cell transcriptome in active multiple sclerosis[J]. Proc Natl Acad Sci USA, 2020, 117: 22932-22943.
[31] Kim SM, Park J, Kim SH, Park SY, Kim JY, Sung JJ, Park KS, Lee KW. Factors associated with the time to next attack in neuromyelitis optica: accelerated failure time models with random effects[J]. PLoS One, 2013, 8: e82325.
[32] Nakashima I, Takahashi T, Cree BA, Kim HJ, Suzuki C, Genain CP, Vincent T, Fujihara K, Itoyama Y, Bar - Or A. Transient increases in anti-aquaporin-4 antibody titers following rituximab treatment in neuromyelitis optica, in association with elevated serum BAFF levels[J]. J Clin Neurosci, 2011, 18: 997-998.
[33] Kowarik MC, Dzieciatkowska M, Wemlinger S, Ritchie AM, Hemmer B, Owens GP, Bennett JL. The cerebrospinal fluid immunoglobulin transcriptome and proteome in neuromyelitis optica reveals central nervous system-specific B cell populations[J]. J Neuroinflammation, 2015, 12: 19.
[34] Cotzomi E, Stathopoulos P, Lee CS, Ritchie AM, Soltys JN, Delmotte FR, Oe T, Sng J, Jiang R, Ma AK, Vander Heiden JA, Kleinstein SH, Levy M, Bennett JL, Meffre E, O'Connor KC. Early B cell tolerance defects in neuromyelitis optica favour anti-AQP4 autoantibody production[J]. Brain, 2019, 142: 1598-1615.
[35] Zhang C, Zhang TX, Liu Y, Jia D, Zeng P, Du C, Yuan M, Liu Q, Wang Y, Shi FD. B - cell compartmental features and molecular basis for therapy in autoimmune disease[J]. Neurol Neuroimmunol Neuroinflamm, 2021, 8: e1070.
[36] Feng J, Fan S, Sun Y, Zhang Z, Ren H, Li W, Cui L, Peng B, Ren X, Zhang W, Guan H, Wang J. Study of B cell repertoire in patients with anti-N-methyl-D-aspartate receptor encephalitis[J]. Front Immunol, 2020, 11: 1539.
[37] Kreye J, Wenke NK, Chayka M, Leubner J, Murugan R, Maier N, Jurek B, Ly LT, Brandl D, Rost BR, Stumpf A, Schulz P, Radbruch H, Hauser AE, Pache F, Meisel A, Harms L, Paul F, Dirnagl U, Garner C, Schmitz D, Wardemann H, Prüss H. Human cerebrospinal fluid monoclonal N - methyl - D - aspartate receptor autoantibodies are sufficient for encephalitis pathogenesis[J]. Brain, 2016, 139(Pt 10): 2641-2652.
[38] Malviya M, Barman S, Golombeck KS, Planagumà J, Mannara F, Strutz-Seebohm N, Wrzos C, Demir F, Baksmeier C, Steckel J, Falk KK, Gross CC, Kovac S, Bönte K, Johnen A, Wandinger KP, Martín-García E, Becker AJ, Elger CE, Klöcker N, Wiendl H, Meuth SG, Hartung HP, Seebohm G, Leypoldt F, Maldonado R, Stadelmann C, Dalmau J, Melzer N, Goebels N. NMDAR encephalitis: passive transfer from man to mouse by a recombinant antibody[J]. Ann Clin Transl Neurol, 2017, 4: 768-783.
[39] Ly LT, Kreye J, Jurek B, Leubner J, Scheibe F, Lemcke J, Wenke NK, Reincke SM, Prüss H. Affinities of human NMDA receptor autoantibodies: implications for disease mechanisms and clinical diagnostics[J]. J Neurol, 2018, 265: 2625-2632.
[40] Wenke NK, Kreye J, Andrzejak E, van Casteren A, Leubner J, Murgueitio MS, Reincke SM, Secker C, Schmidl L, Geis C, Ackermann F, Nikolaus M, Garner CC, Wardemann H, Wolber G, Prüss H. N - methyl - D - aspartate receptor dysfunction by unmutated human antibodies against the NR1 subunit[J]. Ann Neurol, 2019, 85: 771-776.
[41] Owens GP, Ritchie A, Rossi A, Schaller K, Wemlinger S, Schumann H, Shearer A, Verkman AS, Bennett JL. Mutagenesis of the aquaporin 4 extracellular domains defines restricted binding patterns of pathogenic neuromyelitis optica IgG[J]. J Biol Chem, 2015, 290: 12123-12134.
[42] Soltys J, Liu Y, Ritchie A, Wemlinger S, Schaller K, Schumann H, Owens GP, Bennett JL. Membrane assembly of aquaporin - 4 autoantibodies regulates classical complement activation in neuromyelitis optica[J]. J Clin Invest, 2019, 129: 2000-2013.
[43] Wheeler MA, Clark IC, Tjon EC, Li Z, Zandee SEJ, Couturier CP, Watson BR, Scalisi G, Alkwai S, Rothhammer V, Rotem A, Heyman JA, Thaploo S, Sanmarco LM, Ragoussis J, Weitz DA, Petrecca K, Moffitt JR, Becher B, Antel JP, Prat A, Quintana FJ. MAFG - driven astrocytes promote CNS inflammation[J]. Nature, 2020, 578: 593-599.
[44] Stratoulias V, Venero JL, Tremblay MÈ, Joseph B. Microglial subtypes: diversity within the microglial community[J]. EMBO J, 2019, 38: e101997.
[45] Tuzlak S, Dejean AS, Iannacone M, Quintana FJ, Waisman A, Ginhoux F, Korn T, Becher B. Repositioning T H cell polarization from single cytokines to complex help[J]. Nat Immunol, 2021, 22: 1210-1217.

Please choose a citation manager

Content to export