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1、Kounoetal.GenomeBiology2013,14:R118http://genomebiology.com/2013/14/10/R118RESEARCHOpenAccessTemporaldynamicsandtranscriptionalcontrolusingsingle-cellgeneexpressionanalysis1,21,23221,2TsukasaKouno,MichieldeHoon,JessicaCMar,YasuhiroTomaru,MitsuokiKawano,PieroCarninci,1,22,41,2*HarukazuSuzuk
2、i,YoshihideHayashizakiandJayWShinAbstractBackground:Changesinenvironmentalconditionsleadtoexpressionvariationthatmanifestatthelevelofgeneregulatorynetworks.Despiteastrongunderstandingoftherolenoiseplaysinsyntheticbiologicalsystems,itremainsunclearhowpropagationofexpressionheterogeneityinan
3、endogenousregulatorynetworkisdistributedandutilizedbycellstransitioningthroughakeydevelopmentalevent.Results:Hereweinvestigatethetemporaldynamicsofasingle-celltranscriptionalnetworkof45transcriptionfactorsinTHP-1humanmyeloidmonocyticleukemiacellsundergoingdifferentiationtomacrophages.Wesys
4、tematicallymeasuretemporalregulationofexpressionandvariationbyprofiling120singlecellsateightdistincttimepoints,andinferhighlycontrolledregulatorymodulesthroughwhichsignalingoperateswithstochasticeffects.Thisrevealsdynamicandspecificrewiringasacellularstrategyfordifferentiation.Theintegrati
5、onofbothpositiveandnegativeco-expressionnetworksfurtheridentifiestheproto-oncogeneMYBasanetworkhingetomodulateboththepro-andanti-differentiationpathways.Conclusions:Comparedtoaveragedcellpopulations,temporalsingle-cellexpressionprofilingprovidesamuchmorepowerfultechniquetoprobeformechanist
6、icinsightsunderlyingcellulardifferentiation.Webelievethatourapproachwillformthebasisofnovelstrategiestostudytheregulationoftranscriptionatasingle-celllevel.Backgroundintegrationofmotifactivityprofiling,chromatinimmuno-Geneticallyidenticalcellsexposedtothesameenviron-precipiation(ChIP)exper
7、iments,andbymeansofaRNAimentalfactorscanelicitsignificantvariationingeneperturbationmatrix[6-8].Thesestudiesdemonstratedexpressionandphenotype[1].ThisvariabilityissourcedtohowtheTRNiscontrolledbymultipleregulatorsthatstochasticityintranscriptionwherenoiseinthe
