Single-cellRNAsequencingincardiovasculardevelopment,diseaseandmedicineDavidT.Paik1,2,†,SangkyunCho1,2,LeiTian1,2,HowardY.Chang3,4,JosephC.Wu1,2,5,†1StanfordCardiovascularInstitute,Stanford,CA,USA.2DepartmentofMedicine,DivisionofCardiovascularMedicine,StanfordUniversitySchoolofMedicine,Stanford,CA,USA.3CenterforPersonalDynamicRegulomes,StanfordUniversitySchoolofMedicine,Stanford,CA,USA.4DepartmentofGenetics,StanfordUniversitySchoolofMedicine,Stanford,CA,USA.5DepartmentofRadiology,StanfordUniversitySchoolofMedicine,Stanford,CA,USA.AbstractAdvancesinsingle-cellRNAsequencing(scRNA-seq)technologiesinthepast10yearshavehadatransformativeeffectonbiomedicalresearch,enablingtheprofilingandanalysisofthetranscriptomesofsinglecellsatunprecedentedresolutionandthroughput.Specifically,scRNA-seqhasfacilitatedtheidentificationofnovelorrarecelltypes,analysisofsingle-celltrajectoryconstructionandstemorprogenitorcelldifferentiation,andcomparisonofhealthyanddisease-relatedtissuesatsingle-cellresolution.Theseapplicationshavebeencriticalinadvancesincardiovascularresearchinthepastdecade,asevidencedbythegenerationofcellatlasesofmammalianheartandbloodvesselsandtheelucidationofmechanismsinvolvedincardiovasculardevelopmentandstemorprogenitorcelldifferentiation.InthisReview,wesummarizethecurrentlyavailablescRNA-seqtechnologiesandanalyticaltoolsanddiscussthelatestfindingsusingscRNA-seqthathavesubstantiallyimprovedourknowledgeonthedevelopmentofthecardiovascularsystemandthemechanismsunderlyingcardiovasculardiseases.Furthermore,weexamineemergingstrategiesthatintegratemultimodalsingle-cellplatforms,focusingonfutureapplicationsincardiovascularprecisionmedicinethatusesingle-cellomicsapproachesto†dtpaik@stanford.edu;joewu@stanford.edu.AuthorcontributionsD.T.P.andL.T.researcheddataforthearticle,D.T.P.,H.Y.C.andJ.C.W.substantiallycontributedtothediscussionofitscontent,andD.T.P.,S.C.andL.T.wrote,reviewedandeditedthemanuscriptbeforesubmission.CompetinginterestsH.Y.C.isaco-founderofAccentTherapeuticsan...