NucleicAcidsResearch,20191doi:10.1093/nar/gkz199FOXP1circularRNAsustainsmesenchymalstemcellidentityviamicroRNAinhibitionAlessandroCherubini1,MarioBarilani1,2,RiccardoL.Rossi3,MurtadhahM.K.Jalal4,6,FrancescoRusconi1,GiuseppeBuono1,EnricoRagni1,GiovannaCantarella2,5,HamishA.R.W.Simpson4,BrunoP´eault6,7andLorenzaLazzari1,*1LaboratoryofRegenerativeMedicine-CellFactory,DepartmentofTransfusionMedicineandHematology,FondazioneIRCCSCa’GrandaOspedaleMaggiorePoliclinico,Milan,20122,Italy,2DepartmentofClinicalSciencesandCommunityHealth,Universit`adegliStudidiMilano,Milan,20122,Italy,3IstitutoNazionaleGeneticaMolecolare“RomeoedEnricaInvernizzi",Milan,20122Italy,4DepartmentofOrthopaedicSurgery,TheRoyalInfirmaryofEdinburgh,Edinburgh,EH164SA,UK,5DepartmentofOtolaryngology,FondazioneIRCCSCa’GrandaOspedaleMaggiorePoliclinico,Milan,20122,Italy,6MRCCentreforRegenerativeMedicine,TheUniversityofEdinburgh,Edinburgh,EH164UU,UKand7OrthopaedicHospitalResearchCentre,DavidGeffenSchoolofMedicine,UniversityofCaliforniaatLosAngeles,California,90095,USAReceivedJanuary25,2019;RevisedMarch11,2019;EditorialDecisionMarch13,2019;AcceptedMarch18,2019ABSTRACTStemcellidentityandplasticityarecontrolledbymasterregulatorygenesandcomplexcircuitsalsoinvolvingnon-codingRNAs.CircularRNAs(circR-NAs)areaclassofRNAsgeneratedfromprotein-codinggenesbybacksplicing,resultinginstableRNAstructuresdevoidoffree5’and3’ends.Lit-tleisknownofthemechanismsofactionofcircR-NAs,letaloneinstemcellbiology.Inthisstudy,forthefirsttime,wedeterminedthatacircRNAcon-trolsmesenchymalstemcell(MSC)identityanddif-ferentiation.High-throughputMSCexpressionprofil-ingfromdifferenttissuesrevealedalargenumberofexpressedcircRNAs.Amongthose,circFOXP1wasenrichedinMSCscomparedtodifferentiatedmeso-dermalderivatives.SilencingofcircFOXP1dramati-callyimpairedMSCdifferentiationincultureandinvivo.Furthermore,wedemonstratedadirectinter-actionbetweencircFOXP1andmiR-17–3p/miR-127–5p,whichresultsinthemodulationofnon-canonicalWntandEGFRpathways.Finally...
