Single-cellRNA-seqrevealsasignatureofsexualcommitmentinmalariaparasitesAsafPoran1,2,3,*,ChristopherNötzel4,5,*,OmarAly1,2,NuriaMencia-Trinchant1,ChantalT.Harris4,6,MonicaL.Guzman7,DuaneC.Hassane1,OlivierElemento1,2,andBjörnF.C.Kafsack51InstituteforComputationalBiomedicine,DepartmentofPhysiologyandBiophysics,WeillCornellMedicine,NewYork,NY,USA2CarylandIsraelEnglanderInstituteforPrecisionMedicine,WeillCornellMedicine,NewYork,NY,USA3Physiology,BiophysicsandSystemsBiologyGraduateProgram,WeillCornellMedicine,NewYork,NY,USA4Biochemistry,Cell&MolecularBiologyGraduateProgram,WeillCornellMedicine,NewYork,NY,USA5DepartmentofMicrobiology&Immunology,WeillCornellMedicine,NewYork,NY,USA6ImmunologyandMicrobialPathogenesisGraduateProgram,WeillCornellMedicine,NewYork,NY,USA7DivisionofHematology&MedicalOncology,DepartmentofMedicine,WeillCornellMedicine,NewYork,NY,USAPathogenshavetobalancetransmissionwithpersistence.ForPlasmodiumfalciparum,themostwidespreadandvirulentmalariaparasite,persistencewithinitshumanhostrequirescontinuousasexualreplicationwithinredbloodcells(RBCs),whileitsmosquito-bornetransmissiondependsonintra-erythrocyticdifferentiationintonon-replicatingsexualstagescalledgametocytes1.Commitmenttoeitherfateisdeterminedduringtheprecedingcellcyclethatbeginswithinvasionbyasingle,asexually-committedmerozoiteandends,48hourslater,withaschizontreleasingnewlyformedmerozoites,allcommittedtoeithercontinuedasexualreplicationordifferentiationintogametocytes2,3.Sexualcommitmentrequiresactivationofap2-g(PF3D7_1222600)4,5,thetranscriptionalmasterregulatorofsexualdevelopment,fromanepigeneticallysilencedstateduringasexualreplication6,7.Reprintsandpermissionsinformationisavailableatwww.nature.com/reprints.CorrespondenceandrequestsformaterialsshouldbeaddressedtoBK(bjk2007@med.cornell.edu)orOE(ole2001@med.cornell.edu).*Theseauthorscontributedequallytothiswork.Supplementaryinformationislinkedtotheonlineversionofthepaperatwww.nature.com/nature.AuthorContributions:BKconceivedthestudy.AP,CN,a...
