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Table 2. Functional classification of differentially regulated after HOXB4 inactivation in HSC/HPCs Symbol description Fold-change (mean ± SD) Signal transduction Adam8 A disintegrin and metalloprotease domain 8 1.91 ± 0.51 Arl4 ADP-ribosylation factor-like 4 - 1.80 ± 0.40 Dusp6 Dual specificity phosphatase 6 (Mkp3) - 2.30 ± 0.46 Ksr1 suppressor of ras 1 1.92 ± 0.42 Lyst Lysosomal trafficking regulator 1.89 ± 0.34 Mapk1ip1 activated kinase 1 interacting protein 1 1.84 ± 0.22 Narf* Nuclear prelamin A recognition factor 2.12 ± 0.04 Plekha2 Pleckstrin domain-containing. family A. (phosphoinosite 2.15 ± 0.22 binding specific) member 2 Ptp4a2 Protein tyrosine phosphatase 4a2 - 2.04 ± 0.94 Rasa2* RAS p21 activator protein 2 - 2.80 ± 0.13 Rassf4 RAS association (RalGDS/AF-6) domain family 4 3.44 ± 2.56 Rgs18 Regulator of G-protein signaling - 1.93 ± 0.57 Rrad Ras-related associated with diabetes 1.81 ± 0.73 Sh3kbp1 SH3 domain kinase bindings protein 1 - 2.19 ± 0.53 Senp2 SUMO/sentrin specific protease 2 - 1.97 ± 0.49 Socs2 Suppressor of cytokine signaling 2 - 2.82 ± 0.85 Socs5 Suppressor of cytokine signaling 5 2.13 ± 0.08 Socs6 Suppressor of cytokine signaling 6 - 2.18 ± 0.38 Spry1 Sprouty 1 - 2.69 ± 0.19 Sos1 homolog 1 (Drosophila) 2.16 ± 0.71 Ywhag 3-/tryptophan 5- monooxygenase activation protein. - 2.37 ± 1.42 gamma polypeptide Zfyve21 . FYVE domain containing 21 1.93 ± 0.57

Ligands and receptors Bambi BMP and activin membrane-bound inhibitor - 2.94 ± 0.62 Ccr2 Chemokine (C-C) receptor2 - 4.42 ± 3.36 Ccl9 Chemokine (C-C motif)ligand 9 - 2.11 ± 0.89 CD300lp CD300 antigen like family member B 2.71 ± 0.48 Dll1 Delta-like 1 - 2.91 ± 1.89 Gpr43 G protein-coupled 43 1.89 ± 0.75 Icosl Icos ligand 2.83 ± 1.75 IL10rb Interleukin receptor beta 1.75 ± 0.44 IL15 Interleukin 15 2.21 ± 0.35 Ligands and receptors Mox2r* Antigen identified by monoclonal MRc-OX-2 receptor 1.95 ± 0.14 Pde4dip Phosphodiesterase 4D interacting protein (myomegalin) 2.06 ± 0.43 Pdcd1lg1 Programmed cell death ligand 1 2.48 ± 0.97 Ptgir Prostaglandin I receptor 2.16 ± 0.97 Rora RAR-related orphan receptor 2.06 ± 0.62 Trl7 Toll-like receptor 7 2.15 ± 1.23 Tnfrsf1b Tumor necrosis factor receptor superfamily. member 1b 2.72 ± 1.47

Apoptosi s Bcl2l11 BCL2 like-11 2.45 ± 0.01 Bre and reproductive organ expressed protein - 1.87 ± 0.53 Hspa1b* 1b 16.8 ± 3.42 Serpina3g Serine ( or ) protease inhibitor. clade A. member 3G - 1.73 ± 1.73 Tde1 Tumor differentially expressed 1 - 2.40 ± 1.20 Zfx Zinc finger protein X-linked - 1.93 ± 0.45 Cell adhesion/

Flnb Filamin beta 2.14 ± 0.68 Icam1 Intercellular adhesion molecule 1 2.54 ± 1.70 Msn Moesin - 2.03 ± 0.92 Pecam Platelet/endothelial cell adhesion molecule - 2.15 ± 0.09

Cell cycle Btg2 B-cell translocation gene 2 1.75 ± 0.91 Btg3 B-cell translocation gene - 2.37 ± 0.08 Cables Cdk5 and Abl substrate 1 2.13 ± 0.58 Cdkn1a Cyclin-dependent kinase inhibitor 1A (p21) 4.11 ± 0.55 Cdkn1b Cyclin-dependent kinase inhibitor 1B (p27) 1.80 ± 0.25 Ccng2 Cyclin G2 2.70 ± 1.53 Ccni * Cyclin I - 2.07 ± 0.42 Cnnm2 Cyclin M2 3.63 ± 2.90 Ddit3 DNA-damage inducible transcript 3 (Chop10; C/EBP-ζ) 2.42 ± 0.81 Fbxo9 F-box only protein 9 - 2.20 ± 0.45 Gadd45a Growth and DNAdamage inducible 45 alpha 1.65 ± 0.57 Mad Max dimerization protein 4.04 ± 1.56 Mcm3 Minichromosome maintenance deficient 3 - 1.79 ± 0.37

Regulation of

Catnb Catenin beta - 2.11 ± 0.64 Cebpb CCATT/enhancer binding protein (C/EBP) beta 1.95 ± 0.87 Crem* cAMP responsive element modulator 1.83 ± 0.61 Ddit4 DNA-damage inducible transcript 4 5.34 ± 2.66 Erg1 Early growth response - 2.24 ± 0.01 Etv5 Ets variant gene 5 - 1.99 ± 0.05 Foxo3a Forkhead box O3a 2.03 ± 0.41 Hbp1 High mobility group box trancription factor 1 1.72 ± 0.78 Icsbp1 Interferon consensus sequence binding protein 1 2.04 ± 0.95 Jundm2 2 2.17 ± 0.59 Klf3 Krüppel-like factor 3 2.48 ± 0.43 Mecp2 Methyl CpG binding protein 2 1.99 ± 0.63 Ncoa2 2 1.88 ± 0.63 Nfe2 Nuclear factor. erythroid derived 2 2.05 ± 0.45 Nfe2l2 Nuclear factor. erythroid derived 2. like 2 - 2.54 ± 1.02 Nfkb2 Nuclear factor of kappa light polypeptide gene enhancer in B-cells 2. 1.97 ± 0.78 p49/100 Nfkbie* Nuclear factor of kappa light polypeptide gene enhancer in B-cells. 3.17 ± 2.05 inhibitor epsilon Nrip1 Nuclear receptor interacting protein 1 - 1.93 ± 0.59 Tcta T-cell leukemia translocation altered gene 2.13 ± 0.37 Tle1 Transducin-like enhancer of split 1 - 2.25 ± 0.51 Trim27 Tripartite motif 27 (ret finger protein) - 1.86 ± 0.28 Uhrf1 -like. containing PHD and RING finger domains 1 - 1.80 ± 0.78 Zfp82 Zinc finger protein 82 2.09 ± 0.02 Zfp260 Zinc finger protein 260 1.95 ± 0.09 Zfp322a Zinc finger protein 322a 1.79 ± 0.32 Zfp192 Zinc finger protein 192 1.87 ± 0.18

RNA/DNA processing and translation

Cirbp Cold inducible RNA binding protein - 2.05 ± 0.84 Cpeb2 Cytoplasmatic polyadenylation element binding protein 2 - 3.22 ± 2.40 Ddx3x DEAD/H (Asp-Glu-Ala-Asp/His) box polypeptide 3. X-linked - 2.64 ± 0.85 Eif4a1* Eukaryotic translation initiation factor 4A1 - 2.68 ± 1.35 Rad54b Rad54 homolog B (Fsbp) 1.88 ± 0.25 Sfrs5 Splicing factor. argenine/serine-rich 5 (SRp40;HRS) - 2.20 ± 0.17 Slfn8 Schalfen 8 2.11 ± 0.41 U2af1-rs U2 small nuclear ribonucleoprotein auxillary factor (U2AF) 1. related 1.74 ± 0.70 sequence 1

Carriers/transporter

Abcg1 ATP-binding cassette. sub-family G(WHITE).member 1 1.90 ± 0.51 Slc7a11 Solute carrier family 7 (cationic transporter. y+ system). 1.97 ± 1.64 member 11 Slc16a6 Solute carrier family16(monocarboxylicacid transporters).member 16 - 2.85 ± 0.18

Enzymes Dgat1 Diacylglycerol O-acyltransferase 1 1.72 ± 0.57 Hmox1 (decycling) 1 2.43 ± 1.26 Mat2a Methionine adenosyltransferase II - 3.11 ± 1.96 Mgea5* Meningioma expressed antigen 5 (hyaluronidase) - 2.62 ± 0.09 P4ha1 Procollagen-proline. 2-oxoglutarate4-dioxygenase (proline 4- 1.85 ± 0.87 hydroxylase). alpha 1 polypeptide Ptgs2 Prostaglandin-endoperoxidase synthase 2 - 2.38 ± 1.01 Senp7 SUMO/sentrin specific protease 7 1.78 ± 0.38 Siat8d Sialyltransferase 8 (alpha-2. 8- sialyltransferase)D - 2.52 ± 1.30 Shmt1 Serine hydroxymethyl 1 (soluble) - 1.87 ± 0.50

Others Herpud1 Homocysteine-inducible. endoplasmatic reticulum stress-inducible. 1.97 ± 0.71 ubiquitin-like domain member; Hist3h2a* 3. H2a 6.11 ± 5.76 Hspa1a Heat shock protein 1a 3.33 ± 0.21 Irg1 Immunoresponsive gene 1 5.34 ± 5.62 Jmjd1a Jumonji domain containing 1 2.04 ± 0.20 Lpin1 Lpin 1 1.78 ± 0.58 Lrp2bp Lrp2 binding protein 4.92 ± 3.16 Lrrn3 Leucine rich repeat protein 3. neuronal - 2.82 ± 0.51 Mrpl15 Mitochondrial ribosomal protein L 15 - 2.21 ± 0.95 Obfc2a Oligonucleotide/oligosaccharide-binding fold containing 2A 2.40 ± 0.33 Osbpl5 Oxysterol binding protein-like 5 1.74 ± 0.58 Pck2 Phosphoenolpyruvate carboxykinase 2 (mitochondrial) 1.77 ± 0.35 Phf21a PHD finger protein 21A 1.85 ± 0.24 R3hdm1 R3H domain 1 (binds single-stranded nucleic acids) - 2.01 ± 0.13 Rnf135 Ring finger protein 135 1.84 ± 0.24 Others Rsad2 Radical S-adenosyl methionine domain containing 2 2.15 ± 0.43 Sart 2 Squamos cell carcinoma antigen recognized by T cells 2 - 2.22 ± 1.00 Smyd4 SET and MYND domain containing 4 1.76 ± 0.59 Spata 13 Spermatogenesis associated 13 2.04 ± 0.58 Tcta T-cell leukemia translocation altered gene 2.13 ± 0.37 Tex9 Testis expressed gene 9 1.77 ± 0.41 Thap2 THAP domain containing. apoptosis associated protein 2 2.04 ± 0.75 Tmem129 Transmembrane protein 129 2.07 ± 0.06 Tnfaip2* Tumor necrosis factor. alpha-induced protein 2 2.55 ± 1.54 Tnip1 TNFAIP3 interacting protein 1 2.62 ± 1.47 Wdr33 WD repeat domain 33 1.84 ± 0.32 Xist # Inactive X-specific transcripts -3.13

Fold change indicates the average change in 4 h after inactivation of HOXB4ER by tamoxifen- withdrawal in purified Lin -ckit +Sca +1HOXB4ER + cells relative to the associated LSKHOXB4-ER cells cultured in the presence of tamoxifen. Genes were selected based on their reproducibility in magnitude and direction in two independent HOXB4ER-transduced samples. A total of 133 known. unique genes are listed. and genes that were represented by more than one probeset/accession number are denoted by an asterisk (*). Functional annotations are based on and Pubmed. #, A change in gene expression was only observed 1 h after tamoxifen withdrawal but not at later time points.