STANDARD_NAME RIGGI_EWING_SARCOMA_PROGENITOR_UP SYSTEMATIC_NAME M15981 COLLECTION C2:CGP MSIGDB_URL https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/RIGGI_EWING_SARCOMA_PROGENITOR_UP NAMESPACE AFFY_HG_U133 DESCRIPTION_BRIEF Genes up-regulated in mesenchymal stem cells (MSC) engineered to express EWS-FLI1 [GeneID=2130;2321] fusion protein. DESCRIPTION_FULL Ewing's sarcoma family tumors (ESFT) express the EWS-FLI-1 fusion gene generated by the chromosomal translocation t(11;22)(q24;q12). Expression of the EWS-FLI-1 fusion protein in a permissive cellular environment is believed to play a key role in ESFT pathogenesis. However, EWS-FLI-1 induces growth arrest or apoptosis in differentiated primary cells, and the identity of permissive primary human cells that can support its expression and function has until now remained elusive. Here we show that expression of EWS-FLI-1 in human mesenchymal stem cells (hMSC) is not only stably maintained without inhibiting proliferation but also induces a gene expression profile bearing striking similarity to that of ESFT, including genes that are among the highest ESFT discriminators. Expression of EWS-FLI-1 in hMSCs may recapitulate the initial steps of Ewing's sarcoma development, allowing identification of genes that play an important role early in its pathogenesis. Among relevant candidate transcripts induced by EWS-FLI-1 in hMSCs, we found the polycomb group gene EZH2, which we show to play a critical role in Ewing's sarcoma growth. These observations are consistent with our recent findings using mouse mesenchymal progenitor cells and provide compelling evidence that hMSCs are candidate cells of origin of ESFT. PMID 18381423 GEOID AUTHORS Riggi N,Suvà ML,Suvà D,Cironi L,Provero P,Tercier S,Joseph JM,Stehle JC,Baumer K,Kindler V,Stamenkovic I CONTRIBUTOR Jessica Robertson CONTRIBUTOR_ORG MSigDB Team EXACT_SOURCE Suppl. Data 1: hMSCs EWS-FLI1 induced FILTERED_BY_SIMILARITY EXTERNAL_NAMES_FOR_SIMILAR_TERMS EXTERNAL_DETAILS_URL SOURCE_MEMBERS 1552365_at,1552507_at,1552508_at,1552610_a_at,1552611_a_at,1552701_a_at,1552703_s_at,1552791_a_at,1554384_at,1554385_a_at,1554438_at,1554485_s_at,1554524_a_at,1554640_at,1554830_a_at,1555349_a_at,1555480_a_at,1555997_s_at,1556167_at,1558279_a_at,1559280_a_at,1564064_a_at,1569256_a_at,200644_at,200904_at,200905_x_at,200951_s_at,200953_s_at,201075_s_at,201236_s_at,201288_at,201348_at,201562_s_at,201563_at,201565_s_at,201566_x_at,201578_at,201601_x_at,201641_at,201645_at,201648_at,201721_s_at,201743_at,201998_at,202083_s_at,202295_s_at,202388_at,202419_at,202421_at,202478_at,202479_s_at,202501_at,202637_s_at,202638_s_at,202709_at,202718_at,202746_at,202747_s_at,202803_s_at,203085_s_at,203139_at,203234_at,203297_s_at,203298_s_at,203304_at,203320_at,203358_s_at,203394_s_at,203395_s_at,203397_s_at,203413_at,203424_s_at,203549_s_at,203608_at,203615_x_at,203697_at,203698_s_at,203821_at,203836_s_at,203865_s_at,203881_s_at,203929_s_at,203936_s_at,203980_at,203989_x_at,204069_at,204087_s_at,204105_s_at,204137_at,204201_s_at,204223_at,204224_s_at,204229_at,204230_s_at,204249_s_at,204257_at,204320_at,204364_s_at,204365_s_at,204396_s_at,204424_s_at,204463_s_at,204464_s_at,204475_at,204548_at,204604_at,204613_at,204687_at,204748_at,204818_at,204844_at,204869_at,204897_at,204916_at,205016_at,205051_s_at,205065_at,205066_s_at,205081_at,205097_at,205157_s_at,205227_at,205249_at,205259_at,205282_at,205306_x_at,205307_s_at,205316_at,205358_at,205440_s_at,205463_s_at,205500_at,205534_at,205535_s_at,205542_at,205551_at,205637_s_at,205656_at,205659_at,205709_s_at,205721_at,205771_s_at,205786_s_at,205818_at,205824_at,205826_at,205858_at,205883_at,205885_s_at,205901_at,205923_at,205932_s_at,205943_at,205952_at,205959_at,206002_at,206029_at,206059_at,206060_s_at,206067_s_at,206070_s_at,206114_at,206118_at,206164_at,206165_s_at,206190_at,206191_at,206326_at,206481_s_at,206488_s_at,206561_s_at,206565_x_at,206595_at,206644_at,206645_s_at,206655_s_at,206812_at,206866_at,206915_at,207178_s_at,207610_s_at,207630_s_at,207957_s_at,207966_s_at,207980_s_at,208072_s_at,208096_s_at,208180_s_at,208212_s_at,208433_s_at,208490_x_at,208527_x_at,208579_x_at,208605_s_at,208690_s_at,208891_at,208892_s_at,208893_s_at,208933_s_at,208934_s_at,208935_s_at,208936_x_at,208950_s_at,208951_at,208978_at,209071_s_at,209087_x_at,209098_s_at,209189_at,209242_at,209267_s_at,209270_at,209283_at,209291_at,209292_at,209293_x_at,209343_at,209357_at,209457_at,209496_at,209498_at,209505_at,209539_at,209540_at,209541_at,209542_x_at,209555_s_at,209616_s_at,209631_s_at,209652_s_at,209685_s_at,209710_at,209723_at,209785_s_at,209791_at,209840_s_at,209875_s_at,209883_at,209906_at,209911_x_at,209967_s_at,210007_s_at,210107_at,210375_at,210555_s_at,210727_at,210732_s_at,210869_s_at,210904_s_at,210941_at,210963_s_at,210964_s_at,211138_s_at,211178_s_at,211340_s_at,211502_s_at,211577_s_at,211612_s_at,211663_x_at,211748_x_at,211889_x_at,211959_at,212148_at,212187_x_at,212236_x_at,212239_at,212240_s_at,212288_at,212311_at,212382_at,212385_at,212386_at,212402_at,212612_at,212662_at,212713_at,212747_at,213201_s_at,213316_at,213353_at,213416_at,213479_at,213489_at,213524_s_at,213552_at,213620_s_at,213644_at,213721_at,213845_at,213848_at,213931_at,213933_at,214022_s_at,214091_s_at,214111_at,214238_at,214453_s_at,214455_at,214636_at,214807_at,214850_at,214913_at,215043_s_at,215071_s_at,215280_s_at,215299_x_at,215485_s_at,215695_s_at,215856_at,216080_s_at,216222_s_at,216867_s_at,217528_at,217561_at,217757_at,217783_s_at,217979_at,217983_s_at,217984_at,218162_at,218182_s_at,218424_s_at,218559_s_at,218665_at,218695_at,218826_at,218831_s_at,218976_at,219032_x_at,219090_at,219104_at,219250_s_at,219256_s_at,219343_at,219360_s_at,219383_at,219414_at,219427_at,219471_at,219478_at,219528_s_at,219529_at,219572_at,219584_at,219649_at,219682_s_at,219686_at,219737_s_at,219789_at,219825_at,219837_s_at,219855_at,219885_at,219892_at,219908_at,219937_at,220094_s_at,220108_at,220333_at,220356_at,220639_at,220784_s_at,220948_s_at,220984_s_at,221011_s_at,221016_s_at,221039_s_at,221085_at,221236_s_at,221524_s_at,221530_s_at,221552_at,221558_s_at,221577_x_at,221667_s_at,221679_s_at,221854_at,221928_at,221933_at,222067_x_at,222240_s_at,222379_at,222408_s_at,222483_at,222549_at,222557_at,222670_s_at,222760_at,222853_at,222889_at,222895_s_at,222919_at,223058_at,223059_s_at,223177_at,223178_s_at,223226_x_at,223366_at,223484_at,223557_s_at,223623_at,223644_s_at,223809_at,223940_x_at,224325_at,224559_at,224568_x_at,224790_at,224791_at,224909_s_at,224916_at,224925_at,224932_at,224959_at,224963_at,225139_at,225189_s_at,225263_at,225379_at,225447_at,225564_at,225619_at,225622_at,225626_at,225627_s_at,225667_s_at,225809_at,225864_at,225871_at,226106_at,226185_at,226208_at,226283_at,226362_at,226365_at,226492_at,226743_at,226879_at,227006_at,227019_at,227102_at,227109_at,227115_at,227188_at,227190_at,227226_at,227289_at,227318_at,227405_s_at,227410_at,227449_at,227458_at,227490_at,227497_at,227498_at,227610_at,227647_at,227663_at,227677_at,227740_at,227750_at,227790_at,227817_at,227870_at,227875_at,227933_at,227935_s_at,227971_at,227995_at,227996_at,228038_at,228155_at,228159_at,228176_at,228214_at,228224_at,228233_at,228262_at,228329_at,228561_at,228577_x_at,228582_x_at,228636_at,228640_at,228653_at,228665_at,228715_at,228737_at,228766_at,228850_s_at,228854_at,228863_at,228885_at,228952_at,228955_at,228973_at,228988_at,229040_at,229041_s_at,229088_at,229139_at,229240_at,229242_at,229256_at,229269_x_at,229271_x_at,229296_at,229344_x_at,229383_at,229393_at,229485_x_at,229537_at,229553_at,229580_at,229622_at,229779_at,229810_at,229830_at,229850_at,229978_at,230233_at,230303_at,230425_at,230644_at,230650_at,230653_at,230741_at,230782_at,230926_s_at,231382_at,231688_at,231714_s_at,231841_s_at,231842_at,231929_at,232024_at,232035_at,232136_s_at,232226_at,232612_s_at,233562_at,234685_x_at,234799_at,235003_at,235004_at,235044_at,235068_at,235079_at,235108_at,235122_at,235123_at,235306_at,235355_at,235392_at,235456_at,235470_at,235486_at,235787_at,235874_at,235924_at,235944_at,236029_at,236035_at,236088_at,236179_at,236193_at,236277_at,236538_at,236539_at,236597_at,236718_at,236824_at,236945_at,236982_at,238041_at,238123_at,238133_at,238417_at,238727_at,238933_at,238967_at,239132_at,239220_at,239260_at,239261_s_at,239297_at,239650_at,239835_at,240259_at,240950_s_at,241436_at,241946_at,241957_x_at,242767_at,242817_at,242871_at,243366_s_at,243514_at,243856_at,244350_at,244692_at,244885_at,32137_at,336_at,37892_at,38037_at,39248_at,39966_at,43427_at,44790_s_at,45288_at,49452_at,57588_at,58696_at GENE_SYMBOLS SCIN,KCNE4,KCNE4,JAK1,JAK1,CARD16,CASP1,TRDN,PADI2,PADI2,KIAA1217,TMEM37,OLFM3,PALM2AKAP2,STEAP3,ITGB2,FBLIM1,IGFBP5,MROH2A,KDSR,APELA,ATP11B,FAM43B,MARCKSL1,HLA-E,HLA-E,CCND2,CCND2,SMARCC1,BTG2,ARHGDIB,GPX3,SORD,SORD,ID2,,PODXL,IFITM1,BST2,TNC,JAK1,LAPTM5,CD14,ST6GAL1,SEC14L1,CTSH,RGS2,KDSR,IGSF3,TRIB2,TRIB2,MAPRE2,ICAM1,ICAM1,FMOD,IGFBP2,ITM2A,ITM2A,ITGB2,TGFB1,DAPK1,UPP1,JARID2,JARID2,BAMBI,SH2B3,EZH2,HES1,HES1,GALNT3,NELL2,IGFBP5,LPL,ALDH5A1,SULT1A2,FRZB,FRZB,HBEGF,MAP3K5,ADARB1,DMD,MAPT,MMP9,FABP4,F2R,MEIS1,SLC5A6,NRCAM,GPR137B,PTPN13,PRELP,GCH1,SLC17A7,SLC17A7,LMO2,FADS3,COL11A1,REEP1,REEP1,GRK5,LMO3,EDNRA,EDNRA,MMP1,STAR,CDK14,PLCG2,PARM1,PTGS2,HSD17B2,ENPEP,PCSK2,PTGER4,RAMP1,TGFA,KIT,ENPP1,ENPP1,CRIP1,SLC26A2,KRT17,IL1RAP,,NR3C2,LRP8,KMO,KMO,SLC15A2,GRIA2,NPY1R,PDGFA,C5,PCDH7,PCDH7,STEAP1,SV2B,SH3GL3,PCDH17,HDAC9,CDS1,GFRA2,AKAP7,ITGAM,BRINP1,HSPB2,MYOM2,NGFR,ZBTB16,ITGA4,PNOC,RELN,MSX1,TDO2,KCNK3,MMP13,ADGRG2,ANKRD1,ZNF91,PTPN22,WT1,EPHA3,EPHA4,STAT4,CLCA2,CLCA2,GPR17,ENTPD3,GRP,LDB2,CD36,AKR1B10,,CST6,NR0B1,NR0B1,GP1BB,ADRB3,CDH4,NKX2-2,FRK,ADGRE2,CREM,PRKCB,GLG1,CITED2,DGKD,COL21A1,H4C8,ALK,LRP8,H2BC7,H2BC6,H2BC12L,NTRK1,PDLIM1,DUSP6,DUSP6,DUSP6,LGALS8,LGALS8,LGALS8,LGALS8,ALDH7A1,ALDH7A1,CRIP2,RGS5,MCAM,JAG1,FOS,PEG3,SLC39A8,LAMB3,CRYAB,ID4,ID4,ID4,EFHD1,CITED2,DUSP5,RARRES2,CEACAM1,NR2F1,ARHGEF6,IGF1,IGF1,IGF1,CD36,CES1,GPR37,PGF,PRKCB,GATA2,SERPINB9,PLA2G4C,PADI2,LRRN3,SPP1,COLGALT2,C3AR1,H2BC5,CREM,GPD2,CLCA1,PTGER3,NFATC3,CALCA,LGALS8,MCAM,IL13RA1,PCDH7,GYG2,GYG2,KMO,PSTPIP1,MCAM,CDK14,IGF1,IL13RA1,,PTGDS,CEACAM1,IGFBP5,PBX1,PTGDS,KRT17,PIK3R1,PIK3R1,FNBP1,SEL1L3,TCF4,TCF4,TCF4,ZC3H13,RCOR1,PVR,MFAP4,ANKS1A,TNNT1,JCAD,ABCA5,ITGA4,NPTX2,MAPRE2,G0S2,GLCE,ICAM2,CEP112,SOX2,GRIK2,DUSP7,ID2,PTGER3,IFITM1,GPX3,OPCML,GDF7,IFI44,H2BC4,CALCB,PLXDC2,,ADAMTS3,,H2AC6,PPFIA3,SULT1A2,ICAM1,,SIGLEC15,FADS3,MYO10,PDGFA,CLCA2,CALCA,A2M,YPEL5,TSPAN13,RNASET2,RNASET2,OLFML3,CLDN1,STEAP3,MAFB,FZD4,EXOSC4,SLC35F2,FCGRT,DNAJC12,OPN3,SLC24A3,RNF141,FLRT3,SH3TC1,CDC37L1,TRPM4,PRR5L,CLSTN2,FAT4,RUBCNL,WFDC1,BCL11B,CLIC3,CADPS2,PLA1A,ALG6,TBX3,STK32B,PCDH9,NPR3,CYP26B1,CYTL1,NUDT11,SLFN12,TM6SF1,DKK2,TRHDE,MCUR1,GNA14,PAQR5,CORIN,TM4SF20,UTS2,ATP1A1,SLCO5A1,LBH,TCF7L1,ASAP1,TNFSF15,STMN4,RRAGD,BHLHE41,ABHD6,LEF1,GDF15,HSPB8,ABHD6,PKP1,ACACB,NLGN4X,H2BC5,ISYNA1,KCNE4,YPEL5,EFHD2,CLDN1,STMN3,MAFB,ZNF703,FLRT3,DCLRE1B,BCL11B,TRDN,FAM107B,FAM107B,NT5DC1,NT5DC1,SSBP4,ZNF704,C15orf48,TMEFF2,ECRG4,CRYGS,RGS18,MALAT1,FZD8,MALAT1,MALAT1,ASAP1,ASAP1,PREX1,STING1,PREX1,CHCHD10,SLC26A2,SLC26A2,NFATC3,RAPH1,HS6ST1,MAPT,GPD2,SPATA13,SLAIN1,PAG1,PAG1,CACHD1,LRATD1,PARM1,LRATD2,STEAP2,RNF141,CDS1,ZSWIM6,POC1B,,,SEMA6D,SLFN11,HVCN1,PPP1R14A,C1orf226,TRIM35,CYP2R1,LINC02762,EVA1C,TMEM37,MRAP2,PCDH17,TMEM178B,FZD8,FAM43A,EPHA4,CD274,WDFY2,SOX6,SOX6,TSPAN11,KCNE3,,JAK3,UHMK1,KALRN,UBE3D,PRKCB,IGDCC4,KLHL13,LINGO1,PCGF5,NRK,PLXDC2,FARP1,SOX2,PRXL2A,WDFY2,S1PR3,SOX6,PRELP,FREM1,MAP7D2,DAB1,CDC37L1,ODF2L,TALAM1,BHLHE22,PCDH7,SAMD5,CYYR1,ZCCHC12,TOX2,CD36,SLIT2,ZBTB16,PCDH17,MAMDC2,ENPP1,LRP8,DLG2,ZNF711,ITGB2-AS1,ITGB2-AS1,ENPP1,JPH1,ZDHHC21,TNFSF15,PGM2L1,SSBP4,COL11A1,LINC01503,RIMKLB,MARCHF1,L3MBTL3,SHISA3,LMO4,PGM2L1,CLSTN2,ERFE,COL4A4,RSPH3,,KDSR,SHISA9,,SYNPR,EPHB1,LRFN5,SLCO5A1,,P2RX7,SORD,ODF2L,FGF18,MMP8,AP4B1,JCAD,JCAD,IKZF2,GIMAP2,H4C8,CTTNBP2,LRRC4C,ATG16L1,LINC00839,KRTAP4-9,ADARB1,UHMK1,RBM24,CYYR1,ZDHHC21,ZNF704,KCNK3,HIVEP3,,GIMAP8,CSRNP3,,,LSM8,KIAA1549L,CDC37L1,PRSS35,FRK,HMCN1,FAT3,FZD1,NTNG1,CDH11,,,GRIA2,PTPN22,UGT3A1,MYO10,TMEM132B,CCDC171,,TCF12,GABRQ,NTNG1,PGM2L1,ENSG00000288658,,,NOS1,PRSS23-AS1,CORIN,CORIN,TRMT9B,LYPD1,KBTBD8,FLRT2,KASH5,SCNN1G,ZDHHC21,LIN7B,,PGLYRP2,PAQR5,ITGA4,WDFY2,LANCL3,MYO10,CYP4F22,EBF2,JAG2,TBXA2R,COL11A1,HBEGF,AQP3,CSPG5,ACACB,RUBCNL,ABHD6,ACACB,SLC24A3,EXOSC4 FOUNDER_NAMES