Volume 11 Issue 12
Dec.  2020
Turn off MathJax
Article Contents
Xin Shao, Xiaoyan Lu, Jie Liao, Huajun Chen, Xiaohui Fan. New avenues for systematically inferring cellcell communication: through single-cell transcriptomics data[J]. Protein&Cell, 2020, 11(12): 866-880. doi: 10.1007/s13238-020-00727-5
Citation: Xin Shao, Xiaoyan Lu, Jie Liao, Huajun Chen, Xiaohui Fan. New avenues for systematically inferring cellcell communication: through single-cell transcriptomics data[J]. Protein&Cell, 2020, 11(12): 866-880. doi: 10.1007/s13238-020-00727-5

New avenues for systematically inferring cellcell communication: through single-cell transcriptomics data

doi: 10.1007/s13238-020-00727-5

This study was supported by the National Natural Science Foundation of China (Grant Nos. 81774153 and 81973701), the Natural Science Foundation of Zhejiang Province (LZ20H290002), and the National Youth Top-notch Talent Support Program (W02070098).

  • Received Date: 2020-02-04
  • For multicellular organisms, cell-cell communication is essential to numerous biological processes. Drawing upon the latest development of single-cell RNA-sequencing (scRNA-seq), high-resolution transcriptomic data have deepened our understanding of cellular phenotype heterogeneity and composition of complex tissues, which enables systematic cell-cell communication studies at a single-cell level. We first summarize a common workflow of cell-cell communication study using scRNA-seq data, which often includes data preparation, construction of communication networks, and result validation. Two common strategies taken to uncover cell-cell communications are reviewed, e.g., physically vicinal structure-based and ligand-receptor interaction-based one. To conclude, challenges and current applications of cell-cell communication studies at a single-cell resolution are discussed in details and future perspectives are proposed.
  • loading
  • [1]
    Albert R, Jeong H, Barabasi AL (2000) Error and attack tolerance of complex networks. Nature 406:378-382
    Aran D, Looney AP, Liu L, Wu E, Fong V, Hsu A, Chak S, Naikawadi RP, Wolters PJ, Abate AR et al (2019) Reference-based analysis of lung single-cell sequencing reveals a transitional profibrotic macrophage. Nat Immunol 20:163-172
    Bandura DR, Baranov VI, Ornatsky OI, Antonov A, Kinach R, Lou X, Pavlov S, Vorobiev S, Dick JE, Tanner SD (2009) Mass cytometry:technique for real time single cell multitarget immunoassay based on inductively coupled plasma time-of-flight mass spectrometry. Anal Chem 81:6813-6822
    Barabasi AL, Oltvai ZN (2004) Network biology:understanding the cell's functional organization. Nat Rev Genet 5:101-113
    Bessis M (1958) Erythroblastic island, functional unity of bone marrow. Rev Hematol 13:8-11
    Boisset JC, Vivie J, Grun D, Muraro MJ, Lyubimova A, van Oudenaarden A (2018) Mapping the physical network of cellular interactions. Nat Methods 15:547-553
    Braga VM (2002) Cell-cell adhesion and signalling. Curr Opin Cell Biol 14:546-556
    Budnik B, Levy E, Harmange G, Slavov N (2018) SCoPE-MS:mass spectrometry of single mammalian cells quantifies proteome heterogeneity during cell differentiation. Genome Biol 19:161
    Burns JC, Kelly MC, Hoa M, Morell RJ, Kelley MW (2015) Single-cell RNA-Seq resolves cellular complexity in sensory organs from the neonatal inner ear. Nat Commun 6:8557
    Camp JG, Sekine K, Gerber T, Loeffler-Wirth H, Binder H, Gac M, Kanton S, Kageyama J, Damm G, Seehofer D et al (2017)Multilineage communication regulates human liver bud development from pluripotency. Nature 546:533-538
    Cao J, Packer JS, Ramani V, Cusanovich DA, Huynh C, Daza R, Qiu X, Lee C, Furlan SN, Steemers FJ et al (2017) Comprehensive single-cell transcriptional profiling of a multicellular organism.Science 357:661-667
    Cao J, Cusanovich DA, Ramani V, Aghamirzaie D, Pliner HA, Hill AJ, Daza RM, McFaline-Figueroa JL, Packer JS, Christiansen L et al (2018) Joint profiling of chromatin accessibility and gene expression in thousands of single cells. Science 361:1380-1385
    Cheow LF, Courtois ET, Tan Y, Viswanathan R, Xing Q, Tan RZ, Tan DS, Robson P, Loh YH, Quake SR et al (2016) Single-cell multimodal profiling reveals cellular epigenetic heterogeneity. Nat Methods 13:833-836
    Cohen M, Giladi A, Gorki AD, Solodkin DG, Zada M, Hladik A, Miklosi A, Salame TM, Halpern KB, David E et al (2018) Lung single-cell signaling interaction map reveals basophil role in macrophage imprinting. Cell 175:1031-1044 e1018
    Collins BC, Aebersold R (2018) Proteomics goes parallel. Nat Biotechnol 36:1051-1053
    Duan L, Zhang XD, Miao WY, Sun YJ, Xiong G, Wu Q, Li G, Yang P, Yu H, Li H et al (2018) PDGFRbeta cells rapidly relay inflammatory signal from the circulatory system to neurons via chemokine CCL2. Neuron 100:183-200 e188
    Efremova M, Vento-Tormo M, Teichmann SA, Vento-Tormo R (2020)CellPhoneDB:inferring cell-cell communication from combined expression of multi-subunit ligand-receptor complexes. Nat Protoc 15(4):1484-1506
    Eng CL, Lawson M, Zhu Q, Dries R, Koulena N, Takei Y, Yun J, Cronin C, Karp C, Yuan GC et al (2019) Transcriptome-scale super-resolved imaging in tissues by RNA seqFISH. Nature 568:235-239
    Evans WH (2015) Cell communication across gap junctions:a historical perspective and current developments. Biochem Soc Trans 43:450-459
    Fernandez DM, Rahman AH, Fernandez NF, Chudnovskiy A, Amir ED, Amadori L, Khan NS, Wong CK, Shamailova R, Hill CA et al(2019) Single-cell immune landscape of human atherosclerotic plaques. Nat Med 25:1576-1588
    Gao S, Yan L, Wang R, Li J, Yong J, Zhou X, Wei Y, Wu X, Wang X, Fan X et al (2018) Tracing the temporal-spatial transcriptome landscapes of the human fetal digestive tract using single-cell RNA-sequencing. Nat Cell Biol 20:721-734
    Gartner ZJ, Prescher JA, Lavis LD (2017) Unraveling cell-to-cell signaling networks with chemical biology. Nat Chem Biol 13:564-568
    Grun D, Lyubimova A, Kester L, Wiebrands K, Basak O, Sasaki N, Clevers H, van Oudenaarden A (2015) Single-cell messenger RNA sequencing reveals rare intestinal cell types. Nature 525:251-255
    Halpern KB, Shenhav R, Matcovitch-Natan O, Toth B, Lemze D, Golan M, Massasa EE, Baydatch S, Landen S, Moor AE et al(2017) Single-cell spatial reconstruction reveals global division of labour in the mammalian liver. Nature 542:352-356
    Hashimshony T, Wagner F, Sher N, Yanai I (2012) CEL-Seq:singlecell RNA-Seq by multiplexed linear amplification. Cell Rep 2:666-673
    Hu Y, Wang X, Hu B, Mao Y, Chen Y, Yan L, Yong J, Dong J, Wei Y, Wang W et al (2019) Dissecting the transcriptome landscape of the human fetal neural retina and retinal pigment epithelium by single-cell RNA-seq analysis. PLoS Biol 17:e3000365
    Jaitin DA, Kenigsberg E, Keren-Shaul H, Elefant N, Paul F, Zaretsky I, Mildner A, Cohen N, Jung S, Tanay A et al (2014) Massively parallel single-cell RNA-seq for marker-free decomposition of tissues into cell types. Science 343:776-779
    Kirouac DC, Madlambayan GJ, Yu M, Sykes EA, Ito C, Zandstra PW (2009) Cell-cell interaction networks regulate blood stem and progenitor cell fate. Mol Syst Biol 5:293
    Kiselev VY, Yiu A, Hemberg M (2018) scmap:projection of singlecell RNA-seq data across data sets. Nat Methods 15:359-362
    Klein AM, Mazutis L, Akartuna I, Tallapragada N, Veres A, Li V, Peshkin L, Weitz DA, Kirschner MW (2015) Droplet barcoding for single-cell transcriptomics applied to embryonic stem cells. Cell 161:1187-1201
    Kumar V, Donthireddy L, Marvel D, Condamine T, Wang F, LavillaAlonso S, Hashimoto A, Vonteddu P, Behera R, Goins MA et al(2017) Cancer-associated fibroblasts neutralize the anti-tumor effect of CSF1 receptor blockade by inducing PMN-MDSC infiltration of tumors. Cancer Cell 32:654-668 e655
    Kumar MP, Du J, Lagoudas G, Jiao Y, Sawyer A, Drummond DC, Lauffenburger DA, Raue A (2018) Analysis of single-cell RNASeq identifies cell-cell communication associated with tumor characteristics. Cell Rep 25:1458-1468e1454
    Li L, Dong J, Yan L, Yong J, Liu X, Hu Y, Fan X, Wu X, Guo H, Wang X et al (2017) Single-cell RNA-Seq analysis maps development of human germline cells and gonadal niche interactions. Cell Stem Cell 20:858-873 e854
    Liao J, Hao C, Huang W, Shao X, Song Y, Liu L, Ai N, Fan X (2018)Network pharmacology study reveals energy metabolism and apoptosis pathways-mediated cardioprotective effects of Shenqi Fuzheng. J Ethnopharmacol 227:155-165
    Lin X, Spindler TJ, de Souza Fonseca MA, Corona RI, Seo JH, Dezem FS, Li L, Lee JM, Long HW, Sellers TA et al (2019) Superenhancer-associated LncRNA UCA1 interacts directly with AMOT to activate YAP target genes in epithelial ovarian cancer.iScience 17:242-255
    Macosko EZ, Basu A, Satija R, Nemesh J, Shekhar K, Goldman M, Tirosh I, Bialas AR, Kamitaki N, Martersteck EM et al (2015)Highly parallel genome-wide expression profiling of individual cells using nanoliter droplets. Cell 161:1202-1214
    Manwani D, Bieker JJ (2008) The erythroblastic island. Curr Top Dev Biol 82:23-53
    Martin JC, Chang C, Boschetti G, Ungaro R, Giri M, Grout JA, Gettler K, Chuang LS, Nayar S, Greenstein AJ et al (2019)Single-cell analysis of Crohn's disease lesions identifies a pathogenic cellular module associated with resistance to antiTNF therapy. Cell 178:1493-1508 e1420
    Marx V (2019) A dream of single-cell proteomics. Nat Methods 16:809-812
    Mittal K, Eremenko E, Berner O, Elyahu Y, Strominger I, Apelblat D, Nemirovsky A, Spiegel I, Monsonego A (2019) CD4 T cells induce a subset of MHCII-expressing microglia that attenuates Alzheimer pathology. iScience 16:298-311
    Nestorowa S, Hamey FK, Pijuan Sala B, Diamanti E, Shepherd M, Laurenti E, Wilson NK, Kent DG, Gottgens B (2016) A single-cell resolution map of mouse hematopoietic stem and progenitor cell differentiation. Blood 128:e20-31
    Nitzan M, Karaiskos N, Friedman N, Rajewsky N (2019) Gene expression cartography. Nature 576:132-137
    Pan G, Cavalli M, Carlsson B, Skrtic S, Kumar C, Wadelius C (2020)rs953413 Regulates polyunsaturated fatty acid metabolism by modulating ELOVL2 expression. iScience 23:100808
    Petersen F, Bock L, Flad HD, Brandt E (1999) Platelet factor 4-induced neutrophil-endothelial cell interaction:involvement of mechanisms and functional consequences different from those elicited by interleukin-8. Blood 94:4020-4028
    Peterson VM, Zhang KX, Kumar N, Wong J, Li L, Wilson DC, Moore R, McClanahan TK, Sadekova S, Klappenbach JA (2017)Multiplexed quantification of proteins and transcripts in single cells. Nat Biotechnol 35:936-939
    Pfaff DW, Baum MJ (2018) Hormone-dependent medial preoptic/lumbar spinal cord/autonomic coordination supporting male sexual behaviors. Mol Cell Endocrinol 467:21-30
    Picelli S, Bjorklund AK, Faridani OR, Sagasser S, Winberg G, Sandberg R (2013) Smart-seq2 for sensitive full-length transcriptome profiling in single cells. Nat Methods 10:1096-1098
    Rajbhandari P, Arneson D, Hart SK, Ahn IS, Diamante G, Santos LC, Zaghari N, Feng AC, Thomas BJ, Vergnes L et al (2019) Single cell analysis reveals immune cell-adipocyte crosstalk regulating the transcription of thermogenic adipocytes. Elife 8:e49501
    Ramilowski JA, Goldberg T, Harshbarger J, Kloppmann E, Lizio M, Satagopam VP, Itoh M, Kawaji H, Carninci P, Rost B et al (2015)A draft network of ligand-receptor-mediated multicellular signalling in human. Nat Commun 6:7866
    Ramos P, Casu C, Gardenghi S, Breda L, Crielaard BJ, Guy E, Marongiu MF, Gupta R, Levine RL, Abdel-Wahab O et al (2013)Macrophages support pathological erythropoiesis in polycythemia vera and beta-thalassemia. Nat Med 19:437-445
    Rodriques SG, Stickels RR, Goeva A, Martin CA, Murray E, Vanderburg CR, Welch J, Chen LM, Chen F, Macosko EZ (2019) Slide-seq:a scalable technology for measuring genomewide expression at high spatial resolution. Science 363:1463-1467
    Rothbauer M, Zirath H, Ertl P (2018) Recent advances in microfluidic technologies for cell-to-cell interaction studies. Lab Chip 18:249-270
    Satija R, Farrell JA, Gennert D, Schier AF, Regev A (2015) Spatial reconstruction of single-cell gene expression data. Nat Biotechnol 33:495-502
    Scott CL, Guilliams M (2018) Tissue unit-ed:lung cells team up to drive alveolar macrophage development. Cell 175:898-900
    Shalek AK, Satija R, Shuga J, Trombetta JJ, Gennert D, Lu D, Chen P, Gertner RS, Gaublomme JT, Yosef N et al (2014) Single-cell RNA-seq reveals dynamic paracrine control of cellular variation.Nature 510:363-369
    Shao X, Ai N, Xu D, Fan X (2016) Exploring the interaction between Salvia miltiorrhiza and human serum albumin:Insights from herbdrug interaction reports, computational analysis and experimental studies. Spectrochim Acta A Mol Biomol Spectrosc 161:1-7
    Shao X, Lv N, Liao J, Long J, Xue R, Ai N, Xu D, Fan X (2019) Copy number variation is highly correlated with differential gene expression:a pan-cancer study. BMC Med Genet 20:175
    Shao X, Liao J, Lu X, Xue R, Ai N, Fan X (2020) scCATCH:automatic annotation on cell types of clusters from single-cell RNA sequencing data. iScience 23:100882
    Shrestha BR, Chia C, Wu L, Kujawa SG, Liberman MC, Goodrich LV (2018) Sensory neuron diversity in the inner ear is shaped by activity. Cell 174:1229-1246 e1217
    Sicard RE (1986) Hormones, neurosecretions, and growth factors as signal molecules for intercellular communication. Dev Comp Immunol 10:269-272
    Singer SJ (1992) Intercellular communication and cell-cell adhesion.Science 255:1671-1677
    Skelly DA, Squiers GT, McLellan MA, Bolisetty MT, Robson P, Rosenthal NA, Pinto AR (2018) Single-cell transcriptional profiling reveals cellular diversity and intercommunication in the mouse heart. Cell Rep 22:600-610
    Song Y, Xu X, Wang W, Tian T, Zhu Z, Yang C (2019) Single cell transcriptomics:moving towards multi-omics. Analyst 144:3172-3189
    Stagg RB, Fletcher WH (1990) The hormone-induced regulation of contact-dependent cell-cell communication by phosphorylation.Endocr Rev 11:302-325
    Stoeckius M, Hafemeister C, Stephenson W, Houck-Loomis B, Chattopadhyay PK, Swerdlow H, Satija R, Smibert P (2017)Simultaneous epitope and transcriptome measurement in single cells. Nat Methods 14:865-868
    Stuart T, Satija R (2019) Integrative single-cell analysis. Nat Rev Genet 20:257-272
    Sugiyama E, Guerrini MM, Honda K, Hattori Y, Abe M, Kallback P, Andren PE, Tanaka KF, Setou M, Fagarasan S et al (2019)Detection of a high-turnover serotonin circuit in the mouse brain using mass spectrometry imaging. iScience 20:359-372
    Swaminathan J, Boulgakov AA, Hernandez ET, Bardo AM, Bachman JL, Marotta J, Johnson AM, Anslyn EV, Marcotte EM (2018)Highly parallel single-molecule identification of proteins in zeptomole-scale mixtures. Nat Biotechnol 36:1076-1082
    Szczerba BM, Castro-Giner F, Vetter M, Krol I, Gkountela S, Landin J, Scheidmann MC, Donato C, Scherrer R, Singer J et al (2019)Neutrophils escort circulating tumour cells to enable cell cycle progression. Nature 566:553-557
    Tirosh I, Izar B, Prakadan SM, Wadsworth MH 2nd, Treacy D, Trombetta JJ, Rotem A, Rodman C, Lian C, Murphy G et al(2016) Dissecting the multicellular ecosystem of metastatic melanoma by single-cell RNA-seq. Science 352:189-196
    Vento-Tormo R, Efremova M, Botting RA, Turco MY, Vento-Tormo M, Meyer KB, Park JE, Stephenson E, Polanski K, Goncalves A et al(2018) Single-cell reconstruction of the early maternal-fetal interface in humans. Nature 563:347-353
    Vitak SA, Torkenczy KA, Rosenkrantz JL, Fields AJ, Christiansen L, Wong MH, Carbone L, Steemers FJ, Adey A (2017) Sequencing thousands of single-cell genomes with combinatorial indexing.Nat Methods 14:302-308
    Vogel C, Marcotte EM (2012) Insights into the regulation of protein abundance from proteomic and transcriptomic analyses. Nat Rev Genet 13:227-232
    Wang X, Song W, Kawazoe N, Chen G (2013) The osteogenic differentiation of mesenchymal stem cells by controlled cell-cell interaction on micropatterned surfaces. J Biomed Mater Res A 101:3388-3395
    Wang X, Allen WE, Wright MA, Sylwestrak EL, Samusik N, Vesuna S, Evans K, Liu C, Ramakrishnan C, Liu J et al (2018) Threedimensional intact-tissue sequencing of single-cell transcriptional states. Science 361:eaat5691
    Wang S, Karikomi M, MacLean AL, Nie Q (2019) Cell lineage and communication network inference via optimization for single-cell transcriptomics. Nucleic Acids Res 47(11):e66
    Xiong X, Kuang H, Ansari S, Liu T, Gong J, Wang S, Zhao XY, Ji Y, Li C, Guo L et al (2019) Landscape of intercellular crosstalk in healthy and NASH liver revealed by single-cell secretome gene analysis. Mol Cell 75:644-660e645
    Xu Y, Ji K, Wu M, Hao B, Yao KT, Xu Y (2019) A miRNA-HERC4pathway promotes breast tumorigenesis by inactivating tumor suppressor LATS1. Protein Cell 10:595-605
    Xue R, Liao J, Shao X, Han K, Long J, Shao L, Ai N, Fan X (2020)Prediction of adverse drug reactions by combining biomedical tripartite network and graph representation model. Chem Res Toxicol 33:202-210
    Zepp JA, Zacharias WJ, Frank DB, Cavanaugh CA, Zhou S, Morley MP, Morrisey EE (2017) Distinct mesenchymal lineages and niches promote epithelial self-renewal and myofibrogenesis in the lung. Cell 170:1134-1148 e1110
    Zhang L, Vertes A (2018) Single-cell mass spectrometry approaches to explore cellular heterogeneity. Angew Chem Int Ed Engl 57:4466-4477
    Zhang Y, Yan Z, Qin Q, Nisenblat V, Chang HM, Yu Y, Wang T, Lu C, Yang M, Yang S et al (2018) Transcriptome landscape of human folliculogenesis reveals oocyte and granulosa cell interactions.Mol Cell 72:1021-1034 e1024
    Zhang X, Lan Y, Xu J, Quan F, Zhao E, Deng C, Luo T, Xu L, Liao G, Yan M et al (2019) CellMarker:a manually curated resource of cell markers in human and mouse. Nucleic Acids Res 47:D721-D728
    Zhang L, Vertes A (2018) Single-cell mass spectrometry approaches to explore cellular heterogeneity. Angew Chem Int Ed Engl 57:4466-4477
    Zheng GX, Terry JM, Belgrader P, Ryvkin P, Bent ZW, Wilson R, Ziraldo SB, Wheeler TD, McDermott GP, Zhu J et al (2017)Massively parallel digital transcriptional profiling of single cells.Nat Commun 8:14049
    Zheng G, Jiang C, Li Y, Yang D, Ma Y, Zhang B, Li X, Zhang P, Hu X, Zhao X et al (2019) TMEM43-S358L mutation enhances NFkappaB-TGFbeta signal cascade in arrhythmogenic right ventricular dysplasia/cardiomyopathy. Protein Cell 10:104-119
    Zhou B, Liu C, Xu L, Yuan Y, Zhao J, Zhao W, Chen Y, Qiu J, Meng M, Zheng Y et al (2020) N(6)-methyladenosine reader protein Ythdc2 suppresses liver steatosis via regulation of mRNA stability of lipogenic genes. Hepatology. https://doi.org/10.1002/hep.31220
    Zhu C, Preissl S, Ren B (2020) Single-cell multimodal omics:the power of many. Nat Methods 17:11-14
  • 加载中


    通讯作者: 陈斌, bchen63@163.com
    • 1. 

      沈阳化工大学材料科学与工程学院 沈阳 110142

    1. 本站搜索
    2. 百度学术搜索
    3. 万方数据库搜索
    4. CNKI搜索


    Article Metrics

    Article views (335) PDF downloads(60) Cited by()
    Proportional views


    DownLoad:  Full-Size Img  PowerPoint