Apoptosis-Related Gene Expression Profiles of Mouse ESCs and maGSCs Role of Fgf4 and Mnda in Pluripotent Cell Responses to Genotoxicity 英文参考文献.docVIP

Apoptosis-RelatedGeneExpressionProfilesofMouse ESCsandmaGSCs:RoleofFgf4andMndainPluripotent CellResponsestoGenotoxicity TatjanaKhromov1,RalfDressel2,IlianaSiamishi1,JessicaNolte1,LennartOpitz3,WolfgangEngel1,D.V. KrishnaPantakani1* 1Institute of Human Genetics, University of Goettingen, Goettingen, Germany, 2Department of Cellular and Molecular Immunology, University of Goettingen, Goettingen,Germany,3DNAMicroarrayFacility,UniversityofGoettingen,Goettingen,Germany Abstract Stemcellsinthedevelopingembryoproliferateanddifferentiatewhilemaintaininggenomicintegrity,failureofwhichmay lead to accumulation of mutations and subsequent damage to the embryo. Embryonic stem cells (ESCs), the invitro counterpart of embryo stem cells are highly sensitive to genotoxic stress. Defective ESCs undergo either efficient DNA damage repair or apoptosis, thus maintaining genomic integrity. However, the genotoxicity- and apoptosis-related processesingerm-linederivedpluripotentcells,multipotentadultgerm-linestemcells(maGSCs),arecurrentlyunknown. Here,weanalyzedtheexpressionofapoptosis-relatedgenesusingOligoGEArrayinundifferentiatedmaGSCsandESCsand identified a similar set of genes expressed in both cell types. We detected the expression of intrinsic, but not extrinsic, apoptotic pathway genes in both cell types. Further, we found that apoptosis-related gene expression patterns of differentiated ESCs and maGSCs are identical to each other. Comparative analysis revealed that several pro- and anti- apoptotic genes are expressed specifically in pluripotent cells, but markedly downregulated in the differentiated counterparts of these cells. Activation of the intrinsic apoptotic pathway cause approximately ,35% of both ESCs and maGSCstoadoptanearly-apoptoticphenotype.Moreover,weperformedtranscriptomestudiesusingearly-apoptoticcells toidentifynovelpluripotency-andapoptosis-relatedgenes.Fromthesetranscriptomestudies,weselectedFgf4(Fibroblast growthfactor4)andMnda(Myeloidcellnucleardifferentiatin