REVIEWNewavenuesforsystematicallyinferringcell-cellcommunication:throughsingle-celltranscriptomicsdataXinShao1,XiaoyanLu1,JieLiao1,HuajunChen2,3,XiaohuiFan1,4&1CollegeofPharmaceuticalSciences,ZhejiangUniversity,Hangzhou310058,China2CollegeofComputerScienceandTechnology,ZhejiangUniversity,Hangzhou310027,China3TheFirstAffiliatedHospital,SchoolofMedicine,ZhejiangUniversity,Hangzhou310003,China4TheSaveSightInstitute,FacultyofMedicineandHealth,TheUniversityofSydney,Sydney,NSW2000,Australia&Correspondence:fanxh@zju.edu.cn(X.Fan)ReceivedFebruary4,2020AcceptedApril12,2020ABSTRACTFormulticellularorganisms,cell-cellcommunicationisessentialtonumerousbiologicalprocesses.Drawinguponthelatestdevelopmentofsingle-cellRNA-se-quencing(scRNA-seq),high-resolutiontranscriptomicdatahavedeepenedourunderstandingofcellularphe-notypeheterogeneityandcompositionofcomplextis-sues,whichenablessystematiccell-cellcommunicationstudiesatasingle-celllevel.Wefirstsummarizeacommonworkflowofcell-cellcommunicationstudyusingscRNA-seqdata,whichoftenincludesdatapreparation,constructionofcommunicationnetworks,andresultvalidation.Twocommonstrategiestakentouncovercell-cellcommunicationsarereviewed,e.g.,physicallyvicinalstructure-basedandligand-receptorinteraction-basedone.Toconclude,challengesandcurrentapplicationsofcell-cellcommunicationstudiesatasingle-cellresolutionarediscussedindetailsandfutureperspectivesareproposed.KEYWORDScell-cellcommunication,single-cellRNAsequencing,physicalcontact-dependentcommunication,chemicalsignal-dependentcommunication,ligand-receptorinteraction,networkbiologyINTRODUCTIONCell-cellcommunication,alsoknownascell-cellinteraction,isanessentialfeatureofmulticellularorganisms(Singer1992).Thedynamiccommunicatingnetworkformedthroughcommunicationandcooperationbetweencellsplayscrucialrolesinnumerousbiologicalprocesses(Petersenetal.,1999;Kirouacetal.,2009;Wangetal.,2013).Macrophagesinthebonemarrowareknowntodirectlyinteractwithery-throblastsinerythroblasticislandstofacilitatetheirmatura-...
