Replication Timing A Fingerprint for Cell Identity and Pluripotency 英文参考文献.docVIP

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Replication Timing A Fingerprint for Cell Identity and Pluripotency 英文参考文献.doc

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Replication Timing A Fingerprint for Cell Identity and Pluripotency 英文参考文献

ReplicationTiming:AFingerprintforCellIdentityand Pluripotency TyroneRyba1,IchiroHiratani1¤,TakayoSasaki1,DanaBattaglia1,MichaelKulik2,JinfengZhang3, StephenDalton2,DavidM.Gilbert1* 1Department of Biological Science, Florida State University, Tallahassee, Florida, United States of America, 2Department of Biochemistry and Molecular Biology, UniversityofGeorgia,Athens,Georgia,UnitedStatesofAmerica,3DepartmentofStatistics,FloridaStateUniversity,Tallahassee,Florida,UnitedStatesofAmerica Abstract Many types of epigenetic profiling have been used to classify stem cells, stages of cellular differentiation, and cancer subtypes. Existing methods focus on local chromatin features such as DNA methylation and histone modifications that requireextensiveanalysisforgenome-widecoverage.Replicationtiminghasemergedasahighlystablecelltype-specific epigeneticfeaturethatisregulatedatthemegabase-levelandiseasilyandcomprehensivelyanalyzedgenome-wide.Here, wedescribeacellclassificationmethodusing67individualreplicationprofilesfrom34mouseandhumancelllinesand stemcell-derivedtissues,includingnewdataformesendoderm,definitiveendoderm,mesodermandsmoothmuscle.Using aMonte-Carloapproachforselectingfeaturesofreplicationprofilesconservedineachcelltype,weidentify‘‘replication timingfingerprints’’uniquetoeachcelltypeandapplyaknearestneighborapproachtopredictknownandunknowncell types.Ourmethodcorrectlyclassifies67/67independentreplication-timingprofiles,includingthosederivedfromclosely relatedintermediatestages.Wealsoapplythismethodtoderivefingerprintsforpluripotencyinhumanandmousecells. Interestingly,themousepluripotencyfingerprintoverlapsalmostcompletelywithpreviouslyidentifiedgenomicsegments thatswitchfromearlytolatereplicationaspluripotencyislost.Thereafter,replicationtimingandtranscriptionwithinthese regions become difficult to reprogram back topluripotency, suggesting these regions highlightan epigenetic barrier to reprogramming.Inaddition,themajorhistoneclusterHist1consistentlybecomeslaterrepl