SynthetictranscriptionfactorsforcellfatereprogrammingJoshuaBBlack1,2andCharlesAGersbach1,2,3Theabilitytoreprogramcelllineagespecificationthroughtheactivityofmasterregulatorytranscriptionfactorshastransformeddiseasemodeling,drugscreening,andcelltherapyforregenerativemedicine.Recentadvancesintheengineeringofsynthetictranscriptionfactorstomodulateendogenousgeneexpressionnetworksandchromatinstateshavegeneratedanewsetoftoolswithuniqueadvantagestostudyandenhancecellreprogrammingmethods.Severalstudieshaveappliedsynthetictranscriptionfactorsinvariouscellreprogrammingparadigmsinhumanandmurinecells.Moreover,theadaptionofCRISPR-basedtranscriptionfactorsforhigh-throughputscreeningwillenablethesystematicidentificationofoptimalfactorsandgenenetworkperturbationstoimprovecurrentreprogrammingprotocolsandenableconversiontomorediverse,highlyspecified,andmaturecelltypes.Therapiddevelopmentofnext-generationtechnologieswithmorerobustandversatilefunctionalitywillcontinuetoexpandtheapplicationofsynthetictranscriptionfactorsforcellreprogramming.Addresses1DepartmentofBiomedicalEngineering,DukeUniversity,Durham,NC27708,USA2CenterforGenomicandComputationalBiology,DukeUniversity,Durham,NC27708,USA3DepartmentofOrthopaedicSurgery,DukeUniversityMedicalCenter,Durham,NC27710,USACorrespondingauthor:Gersbach,CharlesA(charles.gersbach@duke.edu)CurrentOpinioninGenetics&Development2018,52:13–21ThisreviewcomesfromathemedissueonCellreprogramming,regenerationandrepairEditedbyKnutWoltjenandAlexBortvinhttps://doi.org/10.1016/j.gde.2018.05.0010959-437/ã2018ElsevierLtd.Allrightsreserved.IntroductionTranscriptionfactors(TFs)transformdiverseintracellu-larandextracellularsignalsintodynamicpatternsofgeneexpressionthatdefinecellularphenotype.Duringdevel-opment,theycoordinatetoinitiateandmaintainthetranscriptionalprogramsspecifyingthediversityofcelltypesinanorganism.AsaresultofthenaturalcapacityofTFstoprogramcellstates,ectopicoverexpressionofTFshasbecomeaneffectivestrategytoreprogramcellphe-notypesfordesiredbiom...
