Table 1

Gene sets enriched in CML CD34+ cells following exposure to MSCs and IM

Gene setsNES
FDR
IMMSCCombinedIMMSCCombined
HSC self-renewal       
 TONKS_TARGETS_OF_RUNX1_RUNX1T1_FUSION_HSC_UP 1.5031 2.389541 2.668802 0.200 <0.001 <0.001 
 TAKEDA_TARGETS_OF_NUP98_HOXA9_FUSION_8D_UP 1.539169 2.792789 2.660975 0.180 <0.001 <0.001 
 TAKEDA_TARGETS_OF_NUP98_HOXA9_FUSION_10D_UP 1.172108 2.766266 2.500532 0.508 <0.001 <0.001 
 TONKS_TARGETS_OF_RUNX1_RUNX1T1_FUSION_GRANULOCYTE_UP 1.993256 2.144978 2.329874 0.013 <0.001 <0.001 
 CHEN_HOXA5_TARGETS_9HR_UP 1.612002 1.801589 1.919964 0.127 0.014 0.002 
 IVANOVA_HEMATOPOIESIS_STEM_CELL 1.48788 1.386235 1.660943 0.206 0.151 0.033 
 JAATINEN_HEMATOPOIETIC_STEM_CELL_UP 1.690402 1.326127 1.658947 0.097 0.151 0.033 
 IVANOVA_HEMATOPOIESIS_STEM_CELL_LONG_TERM 1.456441 1.241877 1.370937 0.234 0.268 0.143 
 TAKEDA_TARGETS_OF_NUP98_HOXA9_FUSION_6HR_DN 1.714095 1.645097 1.249897 0.086 0.041 0.243 
HSC quiescence       
 GRAHAM_NORMAL_QUIESCENT_VS_NORMAL_DIVIDING_UP −0.85093 2.016533 2.410049 0.866 0.001 <0.001 
 GRAHAM_CML_QUIESCENT_VS_NORMAL_DIVIDING_UP 1.078994 2.199812 2.085968 0.599 <0.001 <0.001 
 GRAHAM_CML_QUIESCENT_VS_NORMAL_QUIESCENT_UP −1.95649 2.334091 1.929717    
Wnt       
 WNT_SIGNALING 1.644355 1.602941 2.137335 0.111 0.054 <0.001 
 ST_WNT_BETA_CATENIN_PATHWAY 1.186699 1.251462 1.795597 0.492 0.260 0.012 
 KEGG_WNT_SIGNALING_PATHWAY 1.45817 1.374894 1.707158 0.233 0.157 0.023 
 KENNY_CTNNB1_TARGETS_DN −1.36828 1.599336 1.469737 0.211 0.055 0.094 
Cadherin       
 ONDER_CDH1_TARGETS_2_UP 0.921706 1.535746 2.065623 0.822 0.074 0.001 
 ONDER_CDH1_SIGNALING_VIA_CTNNB1 −1.01896 1.318553 1.775083 0.627 0.195 0.014 
 ONDER_CDH1_TARGETS_1_UP 1.462469 1.571189 1.665949 0.229 0.064 0.032 
 ONDER_CDH1_TARGETS_2_DN −1.44575 1.831754 1.64301 0.156 0.011 0.036 
Cytokine signaling       
 SANA_RESPONSE_TO_IFNG_UP −0.95045 2.965142 2.836384 0.726 <0.001 <0.001 
 MOSERLE_IFNA_RESPONSE −0.39523 2.628911 2.578175 1.000 <0.001 <0.001 
 BROWNE_INTERFERON_RESPONSIVE_GENES 0.795554 2.824429 2.561327 0.944 <0.001 <0.001 
 SANA_TNF_SIGNALING_UP −1.19179 2.440201 2.483553 0.383 <0.001 <0.001 
 ZHANG_INTERFERON_RESPONSE −0.82431 2.363861 2.330738 0.893 <0.001 <0.001 
 EINAV_INTERFERON_SIGNATURE_IN_CANCER 0.452984 2.327512 2.303409 1.000 <0.001 <0.001 
 TSENG_IRS1_TARGETS_DN 1.086487 1.9622 2.110712 0.595 0.002 <0.001 
 DAUER_STAT3_TARGETS_DN 0.49214 2.332711 2.044684 1.000 <0.001 0.001 
 KEGG_CYTOKINE_CYTOKINE_RECEPTOR_INTERACTION −1.05504 2.092004 1.973682 0.575 <0.001 0.001 
 DER_IFN_ALPHA_RESPONSE_UP −0.61103 2.152106 1.965927 0.997 <0.001 0.002 
 KEGG_JAK_STAT_SIGNALING_PATHWAY 1.323564 1.822952 1.868087 0.360 0.012 0.004 
 BIOCARTA_INFLAM_PATHWAY −1.03839 1.934039 1.792361 0.600 0.004 0.012 
 DASU_IL6_SIGNALING_SCAR_UP 1.249695 2.034135 1.658946 0.426 0.001 0.033 
 REACTOME_PI3K_AKT_SIGNALING 1.451631 0.752397 1.376669 0.238 0.922 0.139 
 CROONQUIST_NRAS_SIGNALING_DN −2.47053 −1.06302 −1.86165 <0.001 0.667 0.020 
 CROONQUIST_IL6_DEPRIVATION_DN −2.64986 −1.10654 −2.33675 <0.001 0.586 <0.001 
Protein synthesis       
 KEGG_RIBOSOME 2.226323 1.02579 1.438408 0.005 0.552 0.106 
 KRIGE_AMINO_ACID_DEPRIVATION 2.124014 1.422338 1.829972 0.007 0.129 0.008 
Adhesion       
 REACTOME_ADHERENS_JUNCTIONS_INTERACTIONS −0.6271 1.994029 1.614459 0.995 0.002 0.044 
 CROONQUIST_STROMAL_STIMULATION_UP −1.17825 1.87128 2.138987 0.400 0.007 <0.001 
 KEGG_CELL_ADHESION_MOLECULES_CAMS −1.02396 2.055671 2.157459 0.621 0.001 <0.001 
Metabolism       
 KEGG_VALINE_LEUCINE_AND_ISOLEUCINE_DEGRADATION −2.35516 0.562928 −1.52169 <0.001 0.996 0.121 
 KEGG_GLYCOLYSIS_GLUCONEOGENESIS −2.53665 1.257924 −1.82849 <0.001 0.252 0.025 
 KEGG_N_GLYCAN_BIOSYNTHESIS 1.491404 −1.90203 −1.87135 0.206 0.042 0.019 
 KEGG_GLYCOSAMINOGLYCAN_DEGRADATION 0.943999 −1.89651 −2.00295 0.801 0.040 0.007 
 REACTOME_METABOLISM_OF_CARBOHYDRATES −2.04296 0.833918 −2.01312 0.001 0.835 0.007 
 REACTOME_GLUCOSE_METABOLISM −2.31217 0.88233 −2.23553 <0.001 0.771 0.002 
 KEGG_STEROID_BIOSYNTHESIS −2.28708 −1.82998 −2.25745 <0.001 0.052 0.003 
 REACTOME_STEROID_METABOLISM −2.27821 −1.58039 −2.67395 <0.001 0.156 <0.001 
 REACTOME_CHOLESTEROL_BIOSYNTHESIS −2.44969 −1.7996 −2.7018 <0.001 0.063 <0.001 
Cell cycle regulation       
 WU_APOPTOSIS_BY_CDKN1A_VIA_TP53 −2.30721 1.345716 −1.0242 <0.001 0.176 0.607 
 TANG_SENESCENCE_TP53_TARGETS_DN −2.26777 0.669011 −1.25232 <0.001 0.973 0.322 
 CHANG_CYCLING_GENES −2.21082 0.580398 −1.90182 <0.001 0.993 0.014 
 EGUCHI_CELL_CYCLE_RB1_TARGETS −2.00287 −1.28341 −2.06781 0.001 0.375 0.005 
 MOLENAAR_TARGETS_OF_CCND1_AND_CDK4_DN −2.2664 −0.99657 −2.17995 0.000 0.764 0.002 
Gene setsNES
FDR
IMMSCCombinedIMMSCCombined
HSC self-renewal       
 TONKS_TARGETS_OF_RUNX1_RUNX1T1_FUSION_HSC_UP 1.5031 2.389541 2.668802 0.200 <0.001 <0.001 
 TAKEDA_TARGETS_OF_NUP98_HOXA9_FUSION_8D_UP 1.539169 2.792789 2.660975 0.180 <0.001 <0.001 
 TAKEDA_TARGETS_OF_NUP98_HOXA9_FUSION_10D_UP 1.172108 2.766266 2.500532 0.508 <0.001 <0.001 
 TONKS_TARGETS_OF_RUNX1_RUNX1T1_FUSION_GRANULOCYTE_UP 1.993256 2.144978 2.329874 0.013 <0.001 <0.001 
 CHEN_HOXA5_TARGETS_9HR_UP 1.612002 1.801589 1.919964 0.127 0.014 0.002 
 IVANOVA_HEMATOPOIESIS_STEM_CELL 1.48788 1.386235 1.660943 0.206 0.151 0.033 
 JAATINEN_HEMATOPOIETIC_STEM_CELL_UP 1.690402 1.326127 1.658947 0.097 0.151 0.033 
 IVANOVA_HEMATOPOIESIS_STEM_CELL_LONG_TERM 1.456441 1.241877 1.370937 0.234 0.268 0.143 
 TAKEDA_TARGETS_OF_NUP98_HOXA9_FUSION_6HR_DN 1.714095 1.645097 1.249897 0.086 0.041 0.243 
HSC quiescence       
 GRAHAM_NORMAL_QUIESCENT_VS_NORMAL_DIVIDING_UP −0.85093 2.016533 2.410049 0.866 0.001 <0.001 
 GRAHAM_CML_QUIESCENT_VS_NORMAL_DIVIDING_UP 1.078994 2.199812 2.085968 0.599 <0.001 <0.001 
 GRAHAM_CML_QUIESCENT_VS_NORMAL_QUIESCENT_UP −1.95649 2.334091 1.929717    
Wnt       
 WNT_SIGNALING 1.644355 1.602941 2.137335 0.111 0.054 <0.001 
 ST_WNT_BETA_CATENIN_PATHWAY 1.186699 1.251462 1.795597 0.492 0.260 0.012 
 KEGG_WNT_SIGNALING_PATHWAY 1.45817 1.374894 1.707158 0.233 0.157 0.023 
 KENNY_CTNNB1_TARGETS_DN −1.36828 1.599336 1.469737 0.211 0.055 0.094 
Cadherin       
 ONDER_CDH1_TARGETS_2_UP 0.921706 1.535746 2.065623 0.822 0.074 0.001 
 ONDER_CDH1_SIGNALING_VIA_CTNNB1 −1.01896 1.318553 1.775083 0.627 0.195 0.014 
 ONDER_CDH1_TARGETS_1_UP 1.462469 1.571189 1.665949 0.229 0.064 0.032 
 ONDER_CDH1_TARGETS_2_DN −1.44575 1.831754 1.64301 0.156 0.011 0.036 
Cytokine signaling       
 SANA_RESPONSE_TO_IFNG_UP −0.95045 2.965142 2.836384 0.726 <0.001 <0.001 
 MOSERLE_IFNA_RESPONSE −0.39523 2.628911 2.578175 1.000 <0.001 <0.001 
 BROWNE_INTERFERON_RESPONSIVE_GENES 0.795554 2.824429 2.561327 0.944 <0.001 <0.001 
 SANA_TNF_SIGNALING_UP −1.19179 2.440201 2.483553 0.383 <0.001 <0.001 
 ZHANG_INTERFERON_RESPONSE −0.82431 2.363861 2.330738 0.893 <0.001 <0.001 
 EINAV_INTERFERON_SIGNATURE_IN_CANCER 0.452984 2.327512 2.303409 1.000 <0.001 <0.001 
 TSENG_IRS1_TARGETS_DN 1.086487 1.9622 2.110712 0.595 0.002 <0.001 
 DAUER_STAT3_TARGETS_DN 0.49214 2.332711 2.044684 1.000 <0.001 0.001 
 KEGG_CYTOKINE_CYTOKINE_RECEPTOR_INTERACTION −1.05504 2.092004 1.973682 0.575 <0.001 0.001 
 DER_IFN_ALPHA_RESPONSE_UP −0.61103 2.152106 1.965927 0.997 <0.001 0.002 
 KEGG_JAK_STAT_SIGNALING_PATHWAY 1.323564 1.822952 1.868087 0.360 0.012 0.004 
 BIOCARTA_INFLAM_PATHWAY −1.03839 1.934039 1.792361 0.600 0.004 0.012 
 DASU_IL6_SIGNALING_SCAR_UP 1.249695 2.034135 1.658946 0.426 0.001 0.033 
 REACTOME_PI3K_AKT_SIGNALING 1.451631 0.752397 1.376669 0.238 0.922 0.139 
 CROONQUIST_NRAS_SIGNALING_DN −2.47053 −1.06302 −1.86165 <0.001 0.667 0.020 
 CROONQUIST_IL6_DEPRIVATION_DN −2.64986 −1.10654 −2.33675 <0.001 0.586 <0.001 
Protein synthesis       
 KEGG_RIBOSOME 2.226323 1.02579 1.438408 0.005 0.552 0.106 
 KRIGE_AMINO_ACID_DEPRIVATION 2.124014 1.422338 1.829972 0.007 0.129 0.008 
Adhesion       
 REACTOME_ADHERENS_JUNCTIONS_INTERACTIONS −0.6271 1.994029 1.614459 0.995 0.002 0.044 
 CROONQUIST_STROMAL_STIMULATION_UP −1.17825 1.87128 2.138987 0.400 0.007 <0.001 
 KEGG_CELL_ADHESION_MOLECULES_CAMS −1.02396 2.055671 2.157459 0.621 0.001 <0.001 
Metabolism       
 KEGG_VALINE_LEUCINE_AND_ISOLEUCINE_DEGRADATION −2.35516 0.562928 −1.52169 <0.001 0.996 0.121 
 KEGG_GLYCOLYSIS_GLUCONEOGENESIS −2.53665 1.257924 −1.82849 <0.001 0.252 0.025 
 KEGG_N_GLYCAN_BIOSYNTHESIS 1.491404 −1.90203 −1.87135 0.206 0.042 0.019 
 KEGG_GLYCOSAMINOGLYCAN_DEGRADATION 0.943999 −1.89651 −2.00295 0.801 0.040 0.007 
 REACTOME_METABOLISM_OF_CARBOHYDRATES −2.04296 0.833918 −2.01312 0.001 0.835 0.007 
 REACTOME_GLUCOSE_METABOLISM −2.31217 0.88233 −2.23553 <0.001 0.771 0.002 
 KEGG_STEROID_BIOSYNTHESIS −2.28708 −1.82998 −2.25745 <0.001 0.052 0.003 
 REACTOME_STEROID_METABOLISM −2.27821 −1.58039 −2.67395 <0.001 0.156 <0.001 
 REACTOME_CHOLESTEROL_BIOSYNTHESIS −2.44969 −1.7996 −2.7018 <0.001 0.063 <0.001 
Cell cycle regulation       
 WU_APOPTOSIS_BY_CDKN1A_VIA_TP53 −2.30721 1.345716 −1.0242 <0.001 0.176 0.607 
 TANG_SENESCENCE_TP53_TARGETS_DN −2.26777 0.669011 −1.25232 <0.001 0.973 0.322 
 CHANG_CYCLING_GENES −2.21082 0.580398 −1.90182 <0.001 0.993 0.014 
 EGUCHI_CELL_CYCLE_RB1_TARGETS −2.00287 −1.28341 −2.06781 0.001 0.375 0.005 
 MOLENAAR_TARGETS_OF_CCND1_AND_CDK4_DN −2.2664 −0.99657 −2.17995 0.000 0.764 0.002 

NES, Normalized enrichment score.

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