切换至 "中华医学电子期刊资源库"

中华神经创伤外科电子杂志 ›› 2021, Vol. 07 ›› Issue (03) : 156 -160. doi: 10.3877/cma.j.issn.2095-9141.2021.03.007

颅脑与脊髓损伤

单细胞测序分析技术在小胶质细胞表型异质性研究中的最新进展
蔡霖1, 龚秋源1, 王伟1, 田恒力1,()   
  1. 1. 200233 上海,上海交通大学附属第六人民医院神经外科
  • 收稿日期:2021-03-04 出版日期:2021-06-15
  • 通信作者: 田恒力
  • 基金资助:
    国家自然科学基金(81974189,81671207); 上海市科委科技创新行动计划项目(19411968100)

Recent advances of single-cell sequencing technology in microglia phenotypic heterogeneity research

Lin Cai1, Qiuyuan Gong1, Wei Wang1, Hengli Tian1,()   

  1. 1. Department of Neurosurgery, Shanghai Jiaotong University Affiliated Sixth People’s Hospital, Shanghai 200233, China
  • Received:2021-03-04 Published:2021-06-15
  • Corresponding author: Hengli Tian
引用本文:

蔡霖, 龚秋源, 王伟, 田恒力. 单细胞测序分析技术在小胶质细胞表型异质性研究中的最新进展[J/OL]. 中华神经创伤外科电子杂志, 2021, 07(03): 156-160.

Lin Cai, Qiuyuan Gong, Wei Wang, Hengli Tian. Recent advances of single-cell sequencing technology in microglia phenotypic heterogeneity research[J/OL]. Chinese Journal of Neurotraumatic Surgery(Electronic Edition), 2021, 07(03): 156-160.

小胶质细胞(MG)是中枢神经系统(CNS)中的天然免疫巨噬细胞,在神经系统的发育和成熟过程中发挥着重要作用。MG具有显著的表型异质性,可以面对不同的环境变化因素产生一系列反应,进而维持CNS的稳定。目前,仍缺少一种有效且无偏倚的高通量检测技术来评估MG在时间及空间分布中的异质性。随着近年来单细胞技术的发展,以单细胞RNA测序和空间质谱分析为代表的一类高新技术手段极大地促进了对MG异质性的认识和理解。本文将对目前单细胞检测技术在MG异质性方面的研究成果作一综述。

Microglia (MG) are the innate macrophages in the central nervous system (CNS) that play a key role in the processes of development and adulthood of the nervous system. Although MG have been shown to manifest significant phenotypical heterogeneity, which allows them to make a wide range of responses to environmental change for the maintenance of CNS homeostasis. So far, an effective and unbiased and high-throughput method is still lacking to assess the spatial and temporal distribution heterogeneity of MG. The recent emergence of novel single-cell techniques, such as single-cell RNA sequencing and cytometry by time-of-flight mass spectrometry, have greatly promoted our understanding of MG heterogeneity. This article reviews the current knowledge about single-cell sequencing technology in MG heterogeneity research.

[1]
Prinz M, Priller J. Microglia and brain macrophages in the molecular age: from origin to neuropsychiatric disease[J]. Nat Rev Neurosci, 2014, 15(5): 300-312.
[2]
Colonna M, Butovsky O. Microglia function in the central nervous system during health and neurodegeneration[J]. Annu Rev Immunol, 2017, 35: 441-468.
[3]
Prinz M, Jung S, Priller J. Microglia biology: one century of evolving concepts[J]. Cell, 2019, 179(2): 292-311.
[4]
Lawson LJ, Perry VH, Dri P, et al. Heterogeneity in the distribution and morphology of microglia in the normal adult mouse brain[J]. Neuroscience, 1990, 39(1): 151-170.
[5]
Gomez Perdiguero E, Klapproth K, Schulz C, et al. Tissue-resident macrophages originate from yolk-sac-derived erythro-myeloid progenitors[J]. Nature, 2015, 518(7540): 547-551.
[6]
Hoeffel G, Ginhoux F. Ontogeny of tissue-resident macrophages[J]. Front Immunol, 2015, 6: 486.
[7]
Ginhoux F, Greter M, Leboeuf M, et al. Fate mapping analysis reveals that adult microglia derive from primitive macrophages[J]. Science, 2010, 330(6005): 841-845.
[8]
Abiega O, Beccari S, Diaz-Aparicio I, et al. Neuronal hyperactivity disturbs ATP microgradients, impairs microglial motility, and reduces phagocytic receptor expression triggering apoptosis/microglial phagocytosis uncoupling[J]. PLoS Biol, 2016, 14(5): e1002466.
[9]
Rothhammer V, Borucki DM, Tjon EC, et al. Microglial control of astrocytes in response to microbial metabolites[J]. Nature, 2018, 557(7707): 724-728.
[10]
Ueno M, Fujita Y, Tanaka T, et al. Layer V cortical neurons require microglial support for survival during postnatal development[J]. Nat Neurosci, 2013, 16(5): 543-551.
[11]
Arno B, Grassivaro F, Rossi C, et al. Neural progenitor cells orchestrate microglia migration and positioning into the developing cortex[J]. Nat Commun, 2014, 5: 5611.
[12]
党圆圆,张洪钿,徐如祥.小胶质细胞在中枢神经系统创伤后的双重作用及调控机制[J].中华神经创伤外科电子杂志, 2016, 2(5): 305-312.
[13]
Butovsky O, Koronyo-Hamaoui M, Kunis G, et al. Glatiramer acetate fights against Alzheimer’s disease by inducing dendritic-like microglia expressing insulin-like growth factor 1[J]. Proc Natl Acad Sci USA, 2006, 103(31): 11784-11789.
[14]
Keren-Shaul H, Spinrad A, Weiner A, et al. A unique microglia type associated with restricting development of Alzheimer’s disease[J]. Cell, 2017, 169(7): 1276-1290.e17.
[15]
Grun D, Lyubimova A, Kester L, et al. Single-cell messenger rna sequencing reveals rare intestinal cell types[J]. Nature, 2015, 525(7568): 251-255.
[16]
Mrdjen D, Pavlovic A, Hartmann FJ, et al. High-dimensional single-cell mapping of central nervous system immune cells reveals distinct myeloid subsets in health, aging, and disease[J]. Immunity, 2018, 48(3): 599.
[17]
Bottcher C, Schlickeiser S, Sneeboer MAM, et al. Human microglia regional heterogeneity and phenotypes determined by multiplexed single-cell mass cytometry[J]. Nature neurosci, 2019, 22(1): 78-90.
[18]
Prinz M, Erny D, Hagemeyer N. Ontogeny and homeostasis of CNS myeloid cells[J]. Nat Immunol, 2017, 18(4): 385-392.
[19]
Goldmann T, Wieghofer P, Jordao MJ, et al. Origin, fate and dynamics of macrophages at central nervous system interfaces[J]. Nat Immunol, 2016, 17(7): 797-805.
[20]
Jordao MJC, Sankowski R, Brendecke SM, et al. Single-cell profiling identifies myeloid cell subsets with distinct fates during neuroinflammation[J]. Science, 2019, 363(6425): eaat7554.
[21]
Utz SG, See P, Mildenberger W, et al. Early fate defines microglia and non-parenchymal brain macrophage development[J]. Cell, 2020, 181(3): 557-573. e18.
[22]
Arnold TD, Lizama CO, Cautivo KM, et al. Impaired αVβ8 and TGFβ signaling lead to microglial dysmaturation and neuromotor dysfunction[J]. J Exp Med, 2019, 216(4): 900-915.
[23]
Mazaheri F, Breus O, Durdu S, et al. Distinct roles for BAI1 and TIM-4 in the engulfment of dying neurons by microglia[J]. Nat Commun, 2014, 5: 4046.
[24]
Frost JL, Schafer DP. Microglia: architects of the developing nervous system[J]. Trends in cell biology, 2016, 26(8): 587-597.
[25]
Mildner A, Schmidt H, Nitsche M, et al. Microglia in the adult brain arise from ly-6chiccr2+ monocytes only under defined host conditions[J]. Nat Neurosci, 2007, 10(12): 1544-1553.
[26]
Ayata P, Badimon A, Strasburger HJ, et al. Epigenetic regulation of brain region-specific microglia clearance activity[J]. Nature Neurosci, 2018, 21(8): 1049-1060.
[27]
Menassa DA, Gomez-Nicola D. Microglial dynamics during human brain development[J]. Front Immunol, 2018, 9: 1014.
[28]
Goldmann T, Zeller N, Raasch J, et al. Usp18 lack in microglia causes destructive interferonopathy of the mouse brain[J]. EMBO J, 2015, 34(12): 1612-1629.
[29]
Hammond TR, Dufort C, Dissing-Olesen L, et al. Single-cell RNA sequencing of microglia throughout the mouse lifespan and in the injured brain reveals complex cell-state changes[J]. Immunity, 2019, 50(1): 253-271. e6.
[30]
Li Q, Cheng Z, Zhou L, et al. Developmental heterogeneity of microglia and brain myeloid cells revealed by deep single-cell RNA sequencing[J]. Neuron, 2019, 101(2): 207-223. e10.
[31]
Masuda T, Sankowski R, Staszewski O, et al. Spatial and temporal heterogeneity of mouse and human microglia at single-cell resolution[J]. Nature, 2019, 566(7744): 388-392.
[32]
Hagemeyer N, Hanft KM, Akriditou MA, et al. Microglia contribute to normal myelinogenesis and to oligodendrocyte progenitor maintenance during adulthood[J]. Acta neuropathologica, 2017, 134(3): 441-458.
[33]
Krasemann S, Madore C, Cialic R, et al. The trem2-apoe pathway drives the transcriptional phenotype of dysfunctional microglia in neurodegenerative diseases[J]. Immunity, 2017, 47(3): 566-581 e569.
[34]
Grabert K, Michoel T, Karavolos MH, et al. Microglial brain region-dependent diversity and selective regional sensitivities to aging[J]. Nature neuroscience, 2016, 19(3): 504-516.
[35]
Guneykaya D, Ivanov A, Hernandez DP, et al. Transcriptional and translational differences of microglia from male and female brains[J]. Cell Rep, 2018, 24(10): 2773-2783. e6.
[36]
Liddelow SA, Guttenplan KA, Clarke LE, et al. Neurotoxic reactive astrocytes are induced by activated microglia[J]. Nature, 2017, 541(7638): 481-487.
[37]
Sousa C, Golebiewska A, Poovathingal SK, et al. Single-cell transcriptomics reveals distinct inflammation-induced microglia signatures[J]. EMBO reports, 2018, 19(11): e46171.
[38]
Hambardzumyan D, Gutmann DH, Kettenmann H. The role of microglia and macrophages in glioma maintenance and progression[J]. Nat Neurosci, 2016, 19(1): 20-27.
[39]
Galatro TF, Holtman IR, Lerario AM, et al. Transcriptomic analysis of purified human cortical microglia reveals age-associated changes[J]. Nat Neurosci, 2017, 20(8): 1162-1171.
[40]
Zhong S, Zhang S, Fan X, et al. A single-cell RNA-seq survey of the developmental landscape of the human prefrontal cortex[J]. Nature, 2018, 555(7697): 524-528.
[41]
Colonna M, Brioschi S. Neuroinflammation and neurodegeneration in human brain at single-cell resolution[J]. Nat Rev Immunol, 2020, 20(2): 81-82.
[42]
Gosselin D, Skola D, Coufal NG, et al. An environment-dependent transcriptional network specifies human microglia identity[J]. Science, 2017, 356(6344): eaal3222.
[43]
Darmanis S, Sloan SA, Zhang Y, et al. A survey of human brain transcriptome diversity at the single cell level[J]. Proc Natl Acad Sci USA, 2015, 112(23): 7285-7290.
[44]
Sankowski R, Bottcher C, Masuda T, et al. Mapping microglia states in the human brain through the integration of high-dimensional techniques[J]. Nat Neurosci, 2019, 22(12): 2098-2110.
[45]
Salter MW, Stevens B. Microglia emerge as central players in brain disease[J]. Nat Med, 2017, 23(9): 1018-1027.
[46]
Benmamar-Badel A, Owens T, Wlodarczyk A. Protective microglial subset in development, aging, and disease: lessons from transcriptomic studies[J]. Front Immunol, 2020, 11: 430.
[47]
Faissner S, Plemel JR, Gold R, et al. Progressive multiple sclerosis: from pathophysiology to therapeutic strategies[J]. Nat Rev Drug Discov, 2019, 18(12): 905-922.
[48]
Stoeckius M, Hafemeister C, Stephenson W, et al. Simultaneous epitope and transcriptome measurement in single cells[J]. Nat Methods, 2017, 14(9): 865-868.
[1] 丁妍, 文华轩, 陈芷萱, 曾晴, 张梦雨, 廖伊梅, 罗丹丹, 秦越, 梁美玲, 邹于, 李胜利. 胎儿小脑皮质发育不良的产前超声诊断[J/OL]. 中华医学超声杂志(电子版), 2023, 20(03): 255-264.
[2] 丁妍, 文华轩, 张梦雨, 陈思齐, 温昕, 彭桂艳, 曾晴, 罗丹丹, 廖伊梅, 秦越, 梁美玲, 李胜利. 胎儿小脑表面叶裂的产前超声研究[J/OL]. 中华医学超声杂志(电子版), 2023, 20(01): 14-22.
[3] 李玉静, 陈七一, 谢汝明, 陈步东. 获得性免疫缺陷综合征相关原发性中枢神经系统淋巴瘤的预后研究[J/OL]. 中华实验和临床感染病杂志(电子版), 2023, 17(03): 200-208.
[4] 李倩, 邓莉平, 陈果, 张忠威, 莫平征, 胡文佳, 陈良君, 张捷, 张永喜, 杨蓉蓉, 熊勇. 宏基因组二代测序在获得性免疫缺陷综合征合并中枢神经系统感染中的临床应用[J/OL]. 中华实验和临床感染病杂志(电子版), 2023, 17(01): 24-31.
[5] 王欢欢, 郑少祥, 郝金锦, 陈文亮. 胃癌分子分型的研究进展及相关联系[J/OL]. 中华普通外科学文献(电子版), 2024, 18(03): 229-234.
[6] 姜露, 周菊, 毛杨, 代黔. 单细胞和bulk RNA测序的综合分析预测肺鳞状细胞癌治疗反应和预后[J/OL]. 中华肺部疾病杂志(电子版), 2024, 17(04): 535-542.
[7] 杜鑫, 刘霞霞, 张恬波, 张夏林, 杨林花, 张睿娟. AHNAK基因高表达与老年急性髓系白血病患者预后不良相关[J/OL]. 中华细胞与干细胞杂志(电子版), 2024, 14(04): 204-211.
[8] 刘小燕, 龙乾发, 席俊秀, 杜明皓, 黄晓欢. 细胞外囊泡介导的胶质细胞交互作用对神经炎症的调节意义及研究进展[J/OL]. 中华细胞与干细胞杂志(电子版), 2023, 13(04): 235-241.
[9] 程亚飞, 郭航. 中枢神经系统AQP4的调节机制研究进展[J/OL]. 中华神经创伤外科电子杂志, 2024, 10(01): 48-54.
[10] 苏生林, 马金兰, 于弘明, 杨晓军. 单细胞测序技术在脓毒症免疫研究中的应用进展[J/OL]. 中华重症医学电子杂志, 2024, 10(03): 279-286.
[11] 张钊龙, 郑卉, 赵丹阳, 赵悰怡, 刘之琪, 张优佳, 秦秉玉. 趋化因子CXC配体13在中枢神经系统感染中的意义及相关研究进展[J/OL]. 中华重症医学电子杂志, 2024, 10(01): 54-59.
[12] 刘俊彬, 张晓婷, 郭镜培, 刘佳妮, 于本帅, 张可, 周斌. 熊果酸通过抑制NLRP3介导的小胶质细胞焦亡减轻脑缺血再灌注损伤的研究[J/OL]. 中华介入放射学电子杂志, 2024, 12(03): 221-227.
[13] 白鲁岳, 赵思齐, 高升, 杨涛, 孟纯阳. 小胶质细胞极化在神经病理性疼痛发生发展过程中的作用研究进展[J/OL]. 中华诊断学电子杂志, 2023, 11(01): 33-36.
[14] 陆静, 钟为慧, 赵杰, 曾玲晖. 髓系细胞触发受体2在β淀粉样蛋白病理致阿尔茨海默病中的作用机制[J/OL]. 中华老年病研究电子杂志, 2024, 11(01): 51-56.
[15] 王婉杰, 宋文超, 王键, 倪良晨, 洪健, 朱孝成, 姚立彬. 肥胖与中枢神经系统调控的研究进展[J/OL]. 中华肥胖与代谢病电子杂志, 2024, 10(02): 108-112.
阅读次数
全文


摘要