Jmjd1c is Required for MLL-AF9 and HOXA9 Mediated AML Stem Cell Self- Renewal
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1 Supplemental Information Jmjd1c is Required for MLL-AF9 and HOXA9 Mediated AML Stem Cell Self- Renewal Nan Zhu, Mo Chen, Rowena Eng, Joshua DeJong, Amit U. Sinha, Noushin F. Rahnamay, Richard Koche, Fatima Al-Shahrour, Janna C. Minehart, Chun-Wei Chen, Aniruddha J. Deshpande, Haiming Xu, S. Haihua Chu, Benjamin L. Ebert, Robert G. Roeder, Scott A. Armstrong Inventory of Supplemental Information Supplemental Figure Legends Supplemental Figures Figure S1. Related to Figure 1. Figure S. Related to Figure &4. Figure S. Related to Figure &5. Figure S4. Related to Figure 6. Figure S5. Related to Figure 7. Figure S6. Related to Figure 7. Supplemental Tables Table S1. Related to Figure 1. Table S. Related to Figure 1. Table S. Related to Figure S Table S4. Related to Figure. Table S5. Related to Figure 5. Table S6. Related to Figure 7.
2 Figure S1 A B Number of Illumina reads C Log (Median Fold Change Bone Marrow vs. T0) R =0.89 Log (Median Fold Change Spleen vs. T0) Row min Relative Row max D MLL t (8;1) t (15;17) Adult Inv 16 M7 other T_MLL Hoxa9 probe 1 Hoxa9 probe Row relative HOXA9 HOXA10 JMJD1C MEIS1 SENP6 TSCD HIPK HOXA7 CDK6 RDX WNK1 PHIP CHD PDEB RUNX
3 Figure S1. In vivo shrna screen of MLL-AF9 targets. Related to Figure 1. (A) Number of reads obtained from Illumina sequencing of eight experimental replicates. (B) Unsupervised hierarchical clustering of normalized reads of all hairpins in eight replicates. Hairpins are ranked by their depletion level in the bone marrow using log median foldchange. (C) Scatter plot showing correlation of Log Fold Change in the BM vs. SPL. (D) Heatmap of MLL-AF9 target genes (14) (upper panel) and scatter plot of Hoxa9 and Jmjd1c expression level (bottom panel) in human leukemias (9).
4 Figure S A B C Jmjd1c f/f MIT CRE D Jmjd1c f/f :CRE M NTC f/f Jmjd1c f/f :MIT E F G Jmjd1c f/f Jmjd1c -/- H I Cleaved caspase Total H
5 Figure S continued J K L M Cell line HOXA9 expression THP1 + Molm1 + Nomo1 + MonoMac6 + Oci-AML + Kasumi - HL60 - N O
6 Figure S. Effect of loss of Jmjd1c in MLL-AF9 leukemia. Related to Figure &. (A) Colony counts of MLL-AF9 transformed pre-leukemic cells derived from Jmjd1c f/f and wt background 7 days after transduction of CRE or MIT control viruses in methylcellulose. Results from two to three independent experiments. (B) Morphology 9 days after CRE transduction: colony image (top [x40 original magnification]) and Wright- Giemsa staining (bottom [x400 original magnification]). (C) Proliferation assay of sorted GFP+/Tomato+ MLL- AF9 leukemia cells from Jmjd1c f/f (triplicate samples from three leukemias) and wt (triplicate samples) background after transduction with MIT control or CRE virus. (D) Limiting dilution transplantation of cells in (C) see also Table S1. Right panel: Genotyping PCR of BM cells. (E)-(H) Analysis of BM cells from secondary recipient mice. (E) Flow cytometry analysis of c- Kit expression, n=4&7 for Jmjd1c MIT & CRE in BM cells from secondary recipients as in (D). (F) Wright-Giemsa staining of sorted GFP+/Tomato+ (Jmjd1c -/- ) or GFP+ (Jmjd1c f/f ) MLL-AF9 leukemia cells from secondary recipients (x400 original magnification), Colony counts of sorted leukemic cells as in (F) in methylcellulose after 7 days. Duplicate samples from two leukemias are shown. (H) Western blot of cleaved caspase in BM cells as in (F). (I) Colony counts of sorted peripheral blood GFP+ cells in methylcellulose after 7 days from mice transplanted in Figure B 9 days after pipc administration. Duplicate samples from three pipc treated Jmjd1c f/f : Mx1Cre leukemias and a non-treated leukemia are shown. (J) Colony counts of MLL-AF9 transformed pre-leukemic cells derived from Jmjd1c f/f :Vav1Cre and controls. Shown are duplicate samples. (K) Survival curve of primary recipient mice that received,000 MLL-AF9 transformed LSKs from Jmjd1c f/f : Vav1Cre and controls. (L) Proliferation of human leukemia cells transduced with shrna (two independent shrnas were used) against Jmjd1c compared to shluc control, as measured by live cell counts. Results from four independent experiments. (M) RT-QPCR performed using cells from (L). Results from three independent experiments. (N) Apoptosis assay of transduced cells as in (L). Shown are duplicate samples. Color key same as in (L) and different shades of the same color represents different time point: lighter day4 and darker day7. NA: no day7 data available because of insufficient number of cells. (O) Colony counts of Hoxa9/Meis1 transformed pre-leukemic cells derived from Jmjd1c f/f :Vav1Cre and controls. Results from two independent experiments in duplicates. Data are represented as mean+ SEM in (A), (E), (G), (I), (J) & (L)-(O). *p<0.05; **p<0.01 student s t-test.
7 Figure S A f/f NES=1.44 -/- p=0.08 q=0.05 f/f NES=1.7 -/- p=0.06 q=0.08 f/f NES=1. -/- p=0.5 q=0.5 B α-jmjd1c Streptavidin pull down - + 5% Input - + Bio-Jmjd1c Jmjd1c HA-IP flag-jmjd1c + + HA-Hoxa9 - + flag-jmjd1c C Jmjd1c f/f M Jmjd1c -/- HK9me H K9me1 α- Hoxa10 Hoxa10 HA-Hoxa9 Total H 1 4 D Genes negatively regulated by Jmjd1c Genes bound and negatively regulated by Hoxa9 Log Fold change CRE/MIT Genes positively regulated by Jmjd1c Log Fold change CRE/MIT Genes bound and positively regulated by Hoxa9 HK9me CRE/MIT HK9me CRE/MIT E f/f NES= /- p=0.0 q=0.09 f/f NES= /- f/f NES=1.5 -/- p=0.0 q=0.15 p=0.09 q=0.
8 Figure S. Loss of Jmjd1c on gene expression and histone methylation. Related to Figure 4. (A) GSEA analysis result showing enrichment of differentiation and apoptosis pathway in MLL-AF9 leukemia cells 6 days after loss of Jmjd1c. (B) Left panel : Coimmunoprecipitation of HOXA10 and JMJD1C in 9T cells transfected with indicated plasmids. Right panel: In vitro protein-protein interaction assay between purified HA-Hoxa9 from 9T cells and baculovirus system expressed and purified flag-jmjd1c. (C) Western on HK9me/me1 in BM cells from secondary MLL-AF9 recipient mice. (D) Scatter plots of Log gene expression changes (CRE/MIT Y axis) vs. HK9me level. Highlighted in red populations: upper left: genes that are up-regulated upon loss of Jmjd1c; lower left: genes that are down-regulated upon loss of Jmjd1c; upper right: genes that are bound and repressed by Hoxa9; lower right: genes that are bound and activated by Hoxa9 (44). (E) GSEA analysis result showing enrichment of differentiation and negative regulation of cell cycle signatures in Hoxa9/Meis1 leukemia cells 6 days after loss of Jmjd1c.
9 Figure S4 A C B LK LSK GMP CMP MEP c-kit CD48 FcγR II/III Vav1Cre Sca-1 CD150 CD4 Lin- Lin- CLP Flt C-Kit Vav1Cre IL-7Rα Sca-1
10 Figure S4. Effect of loss of Jmjd1c in normal hematopoiesis. Related to Figure 6. (A) RT-QPCR analysis of Jmjd1c level in hematopoietic compartments (n= biological replicates). LT-HSC [LSK Flt - CD4 - ], ST-HSC [LSK Flt - CD4 + ], LMPP [LSK Flt + CD4 + ], CMP [LK CD4 + FcγR II/III lo ], GMP [LK CD4 + FcγR II/III hi ], MEP [LK CD4 - FcγR II/III lo ]. (B) Colony formation of normal hematopoietic progenitors using whole bone marrow from Jmjd1c f/f :Vav1Cre mice. Summary of three independent experiments. (C) Representative stem progenitors flow cytometry plots from (top panel) and Vav1Cre (bottom) mice (LK [Lin - c-kit + ], CLP [Lin - IL7R + Flt + Sca-1 lo c-kit +lo ], HSC [LSK CD150+ CD48-]). Data are represented as mean+ SEM in (A)&(C).
11 Figure S5 A B C Vav1Cre Vav1Cre Vav1Cre 1 Non-competitive transplant D E F Vav1Cre Vav1Cre Vav1Cre Non-competitive transplant G Mac1Gr1 B0 CD Vav1Cre H Vav1Cre I Vav1Cre 1 Competitive transplant J K L Vav1Cre Vav1Cre Vav1Cre M 1 Competitive transplant N Vav1Cre
12 Figure S5 continued O P Jmjd1c f/f Figure S5. Effect of loss of Jmjd1c in regenerative hematopoiesis. Related to Figure 7. (A) -(L) Flow cytometry analysis results of chimerism of recipient mice from transplantation experiments. (A)-(C) Two million BM cells from Vav1Cre or Jmjd1c f/f : Vav1Cre were transplanted into lethally irradiated CD45.1 recipients. (n=10) (D)-(F) Two million BM cells from primary non-competitive transplantation were serially transplanted into secondary CD45.1 recipients (n=10). (G)-(I) Chimerism of PB Mac-1 Gr-1(G), B0 (H) and CD (I) in primary competitive transplant as in Figure 7(A)-(C). (J)-(K) Two hundred HSC (CD150 + CD48 - Lin - Sca-1 + c-kit + ) cells from Vav1Cre or Jmjd1c f/f : Vav1Cre were mixed 1:1 with 00 CD45.1 HSC cells plus 0. million CD45.1 helper cells and transplanted into lethally irradiated CD45.1 recipients. (n=15). Chimerism in peripheral blood (A),(D),(G)- (I)&(J); bone marrow and spleen (B),(E)&(K); stem and progenitor populations in BM (C),(F)&(L). (M) Homing of whole bone marrow from Jmjd1c f/f :Vav1Cre mice analyzed 18 hours after transplantation (n=8). Two donor mice and eight recipients were used. (N) Cell cycle analysis by BrdU and Sytox blue (n= per genotype). (O) HSPC frequency two weeks after 5-Fu treatment (n=-4 per genotype). (P) Survival curve of Jmjd1c f/f : Vav1Cre mice after weekly 5-Fu treatment (indicated by arrows) (n=5 per genotype). Data are represented as mean+ SEM. *p<0.05 student s t-test.
13 Figure S6 A Mx1Cre Jmjd1c f/f Mx1Cre B Mx1Cre Jmjd1c f/f Mx1Cre C Mx1Cre Jmjd1c f/f Mx1Cre 1 Non-competitive transplant D Mx1Cre Jmjd1c f/f Mx1Cre E Mx1Cre Jmjd1c f/f Mx1Cre F Mx1Cre Jmjd1c f/f Mx1Cre 1 Competitive transplant Figure S6 Characterization of loss of Jmjd1c in regenerative hematopoiesis using Mx1Cre system. Related to Figure 7. (A)-(C) Two million BM cells from Mx1Cre or Jmjd1c f/f : Mx1Cre were transplanted into lethally irradiated CD45.1 recipients (n=5). (D)-(F) One million BM cells from Mx1Cre or Jmjd1c f/f : Mx1Cre were mixed 1:1 with CD45.1 BM and transplanted into lethally irradiated CD45.1 recipients (n=5). Chimerism in peripheral blood (A)&(D) ; bone marrow and spleen (B)&(E); stem and progenitor populations in BM (C)& (F). Data are represented as mean+ SEM. *p<0.05 student s t-test.
14 Supplemental Tables Table S1. Related to Figure 1. Genes Targeted in the shrna Screen E01Rik A4Rik E4Rik 41000ORik C0Rik C0Rik Aff1 AI14180 Ankib1 Ano6 Arhgap19 Arid1b Arid Arih Atp11b Bgnt B4galt6 Baz1a Bazb Bcor Bfsp1 Cacnb Cbx Cd47 Cdk17 Cdk6 Cdkn1b Cenpv Chd Chd7 Chd9 Copb1 Crlf Ctnnb1 D90015E06Rik Dach1 Dcun1d1 Dirc Dock8 Dsp Eifa Eif5b Elf1 Emb Erbbip Etv6 F6004A04Rik Fam108b Fam6a Fcho Fhdc1 Frat Fut8 Gda Gfi1 GFP Gm710 Gxylt1 Hectd1 Hhex Hjurp Hnrpll Hoxa10 Hoxa11 Hoxa Hoxa7 Hoxa9 Hpgd Hsd17b11 Ift80 Ikzf1 Il1a Jmjd1c Kctd1 Kif11 Klhdc Krit1 lacz Lass Lass6 Lmo Lnpep Lrrc Lta4h LUCIFERASE March7 Mbnl1 Meis1 Mgat Mgat5 Mppe1 Mrp6 Mtus1 Myb N4bp Naa16 Ncor1 Nipbl Npr1 Nrg Parp8 Pdeb Pds5a Pex1 Pgd Phtf1 Pigl Pitpnc1 Poli Prkarb Psma1 Pus10 Rap1gds1 Rdx Reep Rev1 RFP Rhob Rnf1 Rnf0 Rod1 Rpl6al Rreb1 Rsbn1l Runx Satb Serp1 Sfi1 Sgk Siah Six1 Six4 Slc8a1 Sltm Smc4 Snx1 Snx9 Sos Stxbp5 Supth Susd1 Tmem181a Tnpo1 Trim Trim59 Trip4 Trpm8 Tscd Ubek Ugt1a1 Vcpip1 Vps54 Wbp4 Zcchc
15 Table S. Related to Figure 1. Positive hits in the shrna screen Gene Symbol March E01Rik A4Rik C0Rik Ano6 Arid1b Arid Atp11b B4galt6 Bcor Cbx Cdk17 Cenpv Chd Chd7 Copb1 D90015E06Rik Dcun1d1 Dirc Eifa Eif5b Erbbip Etv6 Fam6a Fhdc1 Gda Gfi1 Gm710 Gxylt1 Hectd1 Hhex Hnrpll #shrnas Depleted >10-fold in BM Gene Symbol Hoxa10 Hoxa11 Hoxa9 Hsd17b11 Ift80 Il1a Jmjd1c Kif11 Klhdc Lass Lmo Lrrc Meis1 Mgat Mppe1 Mrp6 Mtus1 Ncor1 Nipbl Npr1 Nrg Parp8 Pds5a Pex1 Phtf1 Pitpnc1 Poli Prkarb Psma1 Pus10 Rap1gds1 Rdx #shrnas Depleted >10-fold in BM
16 Gene Symbol Reep Rev1 Rnf1 Rod1 Rreb1 Rsbn1l Satb Serp1 Sfi1 Siah Six1 Six4 #shrnas Depleted >10-fold in BM 5 Gene Symbol Smc4 Sos Supth Tnpo1 Trim59 Tscd Ubek Ugt1a1 Vcpip1 Vps54 Wbp4 Zcchc #shrnas Depleted >10-fold in BM
17 Table S. Limiting dilution assay result of MLL-AF9 leukemia Dose Response/Tested P value MIT CRE MIT vs Cre 00,000 6/6 4/ ,000 6/6 6/ ,000 7/8 6/ ,000 5/8 / LIC frequency 1 in 7,000 1 in 5,000
18 Table S4. Related to Figure. Differentially regulated genes (fold> 1.5, p<0.05), between Jmjd1c f/f and Jmjd1c -/- Mll-AF9 leukemic cells Log fold Adjusted Jmjd1c E-15 Slc8a E-06 Cbx E-06 Celsr E-06 Pak E-06 Gm E-05 Ascl E-05 Cbs E-05 Ogdhl Fam1a Snhg Ms4a Wdr Adrbk B4galnt Megf Sarm Dancr Docg Rab Tbc1d Smpd Nefh Spag Fam69b Bcl7a Gga Lmo Elfn Shd Lzts Gtdc Log fold Adjusted Arhgef Slc9a Arhgef Samd Snord Gspt Prickle Art O09Rik Cdh Acer Arxes Pcdhgb Pcdhga Cftr Ltbp Bhlhb Rtn4r Pcdhgb Unc Pcdhgb Alms1-ps Cabp Pcdhga Gria Itgb E-7 Abca E-5 Rcbtb E- Ablim E-0 Gas E-18 Abcg E-16 Thbd E-1
19 Log fold Adjusted Ptplad E-1 Galnt E-11 Clec4a E-11 Chn E-10 Tgfbr E-09 Emb E-09 Hpse E-08 Eps E-08 Bank E-08 Gapt E-08 Arhgap E-08 Dab E-07 Sema4d E-07 Milr E-07 Rab E-07 Tuba E-07 Tmcc E-07 Ptgs E P16Rik E-06 Tpm E-06 Pikcg E-06 Cd E-06 Dse E-06 Irf E-06 Rgl E-05 Dpep E-05 Cd E-05 Psap E-05 Siglec E-05 Ahr E-05 Trps E-05 Cytip E-05 Log fold Adjusted Prx E-05 Clec4a Pry Rassf Gm Itgb Casp Il Stgal Tlr Gm Cdkn1a Csfrb Cd Cd Mgst Rapb H11Rik Gpr Ninj Tlr Tlr Myo1e Tpd Neurl Mafb Vwa5a Ssxb Gngt Cd Csfrb Hmox
20 Log fold Adjusted Ston GRik Plk Tnfsf O0Rik Rgs Lrp Pde7b Abcc P10Rik Trp5inp Camkk Nov Prr5l Htra Sc5d Mndal Lair Slc9a Cpeb Kcnn Haao Gm Bmf Ms4a Slc5a Tle Zfp Mr Ptafr Cxcl Rara Log fold Adjusted Fblim Cd Smim Nos Hlx Pde8b Vwf F1a Trem Ugt1a7c A600H0Rik Gfra Gm Tscd Angptl Gfi1b Zmat Filip1l Cd00lb Sirpa Mgam Arhgef Gal Mx Parp Ugt1a Ugt1a Ugt1a Ugt1a Ugt1a Fbp Ppt
21 Log fold Adjusted Ugt1a6b Ugt1a6a Clvs Ndst Ptkb Nxpe Arhgap AU Il1rb A1cf Trim Lct Cgn Emp Abhd Serpinaf Smad Ubel F04Rik C1qc Krt Klk1b Adamts Irs A7000M07Rik Rhov Mefv Oas Socs Igf Gm Gbp Log fold Adjusted Lrp Tcf7l AF S100a Stat Gdpd BC Ndrg Tubb Zch1d Slc5a Lpar Asb Ap5s Siglec Rasgrp Klk1b Lif Denndc Krt Gng Ptpro Klk1b Klk1b Tspan Cd00e Fgf Maf Fcrls Plcb Nlrp1b Ceacam
22 Log fold Adjusted Klk1b Hbegf Sulf Il Iqgap Trim Ssxb Gm Trim0d Nlrp1a Insl Ccrl
23 Table S5. Related to Figure 5. Differentially regulated genes (fold> 1.5, p<0.05), between Jmjd1c f/f and Jmjd1c -/- Hoxa9/Meis1 leukemic cells Log fold Adjusted Pcdh E-11 Plekhh E-09 Eltd E-08 Armcx E-06 Cth E-06 Zcchc E-06 Fam174b E-05 Aldh1l Gm Pcdhgc Glyat Rgs Mir17hg Sgip Kdelc Prrg Ggact Slc6a Sacs Ccdc Hid Pitpnm Cdrl Ctnna Col5a Nr0b Six Hmgn Cpeb Extl Aldh1a B1004C11Rik Log fold Adjusted N06Rik Tacc Tfr Pcsk Msantd Spry Dab E-5 Wfdc E-4 Cd E- Rgl E-1 Tlr E-1 Itgb E-19 Tscd E-19 Ndrg E-18 C1qb E-18 Msr E-18 Fyb E-18 Gpnmb E-18 Sdc E-17 Pira E-16 Gm E-16 Hmox E-16 Pira E-15 Pira E-15 Bank E-15 Abca E-15 Car E-4 Ctss E-40 Pira E-1 Pira E-7 Fos E-6 AI E-6
24 Log fold Adjusted Rara E-15 Tgfbi E-14 Stk17b E-14 Ahnak E-14 Rap1gap E-14 Gas E-1 Hlx E-1 C1qc E-1 Sema4d E-1 Plek E-1 Arl4c E-1 Abcg E-1 Ifi E-1 C1qa E-1 Ptpro E-1 Ccl E-1 Ifi7la E-1 Lgmn E-1 Chn E-1 Slfn E-1 Fosl E-1 Id E-1 Zfp E-1 Mir E-1 Lpl E-1 Marcks E-11 Trem E-11 Gapt E-11 Fcgr E-11 Mpeg E-11 Mapk E-11 Spint E-11 Log fold Adjusted Itgb E-10 Abi E-10 Maf E-10 Pira E-10 Olfm E-10 Oas E-10 Ifit E-10 Tpd E-09 Ms4a4c E-09 Lrrc E-09 Nlrp E-09 Cd E-09 Adorab E-09 Asph E-09 Il10ra E-09 Shdc E-09 Slc15a E-09 Cd00r E-09 Lgals E-09 Ier E-08 Abcg E-08 Clec4a E-08 Jun E-08 Htra E-08 Psap E-08 Pry E-08 Ptgs E-08 Rcbtb E-08 Xdh E-08 Ptafr E-08 Mmp E-08 Mtss E-08
25 Log fold Adjusted Ddx E-06 Atp7a E-06 Hpse E-06 AF E-06 Dusp E-06 Krt E-06 Egr E-06 Egr E-06 Tnfaip E-06 Plxdc E-06 Stk E-06 Ccr E-06 Galnt E-06 Gm E-06 Nrp E-06 Zbp E-06 Btg E-06 Csf E-06 Il6ra E-06 Rasgrp E-06 Neurl E-06 Ndst E-06 Klf E-06 Myof E-06 Trim0d E-06 Slca E-06 Mapk E-06 Phospho E-06 Rbms E-06 B4006N0Rik E-06 Stx E-06 Lyn E-05 Log fold Adjusted Serpinb E-05 Slfn E-05 Nt5e E-05 Klf E-05 Mitf E-05 Cd E-05 Sfxn E-05 Tnfrsf E-05 Zch1d E-05 Dse E-05 Ifit E-05 Vcan E-05 Cd E-05 H-DMb E-05 Emp E-05 Oit E-05 Lilra E-05 Nos E P16Rik E-05 Evia E-05 Wipi E-05 Sgms E-05 AA E-05 Ahr E-05 Gbp E-05 Plaur E-05 Pydc E-05 Siglec E-05 Ankrdb E-05 Lif E-05 Clvs E-05 Tlr E-05
26 Log fold Adjusted Bcll E-05 Zfhx E-05 Ifnlr Osgin Gcnt Hgf Gsn Cox4i Trim0b Pikr Dusp Ms4a6c Gm Tnip Cd Pry N05Rik Adora Upp Mylk Ly6g5b Samhd Pry Cd00ld Fam19a Arhgef Grina Csf1r Pirb Zcwpw Fam49a Pikr Log fold Adjusted Klk1b Tlr Card Cd Tgm Hbegf Arg Prx Susd Tagap Ccl Tgfbr Havcr Serpinb Anxa LOC Anxa Mnda Adam Card Lsp Cdc4ep Nfkbiz Mir Tesc Cnr Spatc F04Rik Dfna Pag Pgf Smpd
27 Log fold Adjusted Rassf Zmat Rab AI Ublcp Gpr Serpinaf Clec7a Gm Epb4.1l Mertk Slc7a Klra Usp Gbp Tulp Tnfrsf Lyz Bcla1b Gp49a Prr Scel Tnfsf Rnase Bmf Itpr Il1r Saa Il1b Galnt Nov Cpeb Log fold Adjusted Cd Pf Sulf Nedd Ptms Myo1e Mctp D18Rik Aif Atf Dpep Sirpb1b Kcne Zfp6l Wfdc Rnf Arg Nos1ap Tmcc Ly6a Nrg Adoraa Irgc Scn1b Ceacam Antxr Gpr Ccdc Clec4n Mar Bcla1d Cd00lf
28 Log fold Adjusted Slc7a Lifr Cd00c M1Rik Abtb Grk Ppp1rd Rhov Axl Il1rb Plk Gm Klk1b H-Eb Slc44a Dhrs Epma Fas Phlda Scrg H-Aa Ctse Hck Sycp Mir Reps Fcnb Tlr Bcla1a Gm Klk1b Cyp4f Gas Log fold Adjusted Camk1d Tnfsf Il18r Ipcef GRik Creb C0046G1Rik Rragd D0Rik Col1a Il C1006I1Rik Plxna L05Rik Clec4b Kcnk Inhba Rasgrp Arl5c Car Ltb A600H0Rik Pilrb Trp5inp Ppp1r16b Lpcat Mir Grap Pikcb Tg Mapk Mxd Gm Jmjd1c ranks #14 in all down-regulated genes with Log fold change of and adjusted p value of.86e-05.
29 Table S6. Related to Figure 7. Differentially regulated genes (fold> 1.5, p<0.05) in LSK cells between Vav1Cre and Jmjd1c f/f :Vav1Cre mice Log fold Adjusted Wdfy E-1 Ly6c E-11 Jmjd1c E-09 Gm E-06 Fn Fcnb Ighgc Clec1a Gimap Rnase Il7r Ccl Hepacam Ighv F1a Chtf E-06 Prep E-05 Ints E-05 Ppif E-05 Ncdn Igfbp Sfb Clnk Cad Cd Atf6b Ppa Mri Srrt Nop Med Gtdc Log fold Adjusted Ptk Tcof Rae Lmnb Tcf BC Runx Igkv Sumf Eifb Zfp Cdc Ubap Prpsap Pkmyt Emid Arhgef Il1rb Vars Sf Eifb Padi Znhit Tbc1d9b Ttyh Impdh Vps7b Cdk Uaf Phrf Cpne Polra
30 Log fold Adjusted Mybl Itgab Med Mgat Pola
NES: normalized enrichment score (analyzed using KEGG pathway gene sets in the GSEA software); FDR:
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