Supplemental Figures and Figure Legends
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Supplemental Figures and Figure Legends A Source Hirst REMC 1 Source Hirst REMC Source Hirst Source 1 0.9 0.8 0.7 0.6 0.9 REMC 1 0.9 0.8 0.7 0.6 Source Source B Penis_Foreskin_Melanocyte_Primary_Cells_skin03 Penis_Foreskin_Melanocyte_Primary_Cells_skin01 Penis_Foreskin_Melanocyte_Primary_Cells_skin03 0.8HUVEC Penis_Foreskin_Melanocyte_Primary_Cells_skin01 Penis_Foreskin_Fibroblast_Primary_Cells_skin02 Penis_Foreskin_Fibroblast_Primary_Cells_skin01 HUVEC H1_Derived_Mesenchymal_Stem_Cells Penis_Foreskin_Fibroblast_Primary_Cells_skin02 NHLF 0.7HSMM Penis_Foreskin_Fibroblast_Primary_Cells_skin01 Universal_Human_Reference H1_Derived_Mesenchymal_Stem_Cells NHEK Breast_vHMEC NHLF HMEC HSMM Penis_Foreskin_Keratinocyte_Primary_Cells_skin03 0.6Penis_Foreskin_Keratinocyte_Primary_Cells_skin02 Universal_Human_Reference Breast_Myoepithelial_Cells NHEK HELA A549 Breast_vHMEC HEPG2 HMEC hESC_Derived_CD56+_Mesoderm_Cultured_Cells H1_BMP4_Derived_Trophoblast_Cultured_Cells Penis_Foreskin_Keratinocyte_Primary_Cells_skin03 HUES64_Cell_Line Penis_Foreskin_Keratinocyte_Primary_Cells_skin02 H1_BMP4_Derived_Mesendoderm_Cultured_Cells Breast_Myoepithelial_Cells 4star H1_Cell_Line HELA hESC_Derived_CD56+_Ectoderm_Cultured_Cells A549 H1_Derived_Neuronal_Progenitor_Cultured_Cells hESC_Derived_CD184+_Endoderm_Cultured_Cells HEPG2 Neurosphere_Cultured_Cells_Ganglionic_Eminence_Derived hESC_Derived_CD56+_Mesoderm_Cultured_Cells Neurosphere_Cultured_Cells_Cortex_Derived Brain_Germinal_Matrix H1_BMP4_Derived_Trophoblast_Cultured_Cells Fetal_Brain_Female HUES64_Cell_Line Brain_Hippocampus_Middle Pancreas H1_BMP4_Derived_Mesendoderm_Cultured_Cells Pancreatic_Islets 4star Fetal_Intestine_Small Fetal_Intestine_Large H1_Cell_Line Lung hESC_Derived_CD56+_Ectoderm_Cultured_Cells Gastric Esophagus H1_Derived_Neuronal_Progenitor_Cultured_Cells Small_Intestine hESC_Derived_CD184+_Endoderm_Cultured_Cells Sigmoid_Colon Aorta Neurosphere_Cultured_Cells_Ganglionic_Eminence_Derived Right_Ventricle Neurosphere_Cultured_Cells_Cortex_Derived Left_Ventricle Brain_Germinal_Matrix Right_Atrium Psoas_Muscle Fetal_Brain_Female Ovary Brain_Hippocampus_Middle Spleen Thymus Pancreas Adult_Liver Pancreatic_Islets K562 GM12878 Cluster Blood Fetal_Intestine_Small Erythroid Fetal_Intestine_Large BCell Monocyte Lung CD8_Naive_Primary_Cells Gastric CD4_Naive_Primary_Cells CD4_Memory_Primary_Cells Esophagus TCell2 Small_Intestine TCell1 Peripheral_Blood_Mononuclear_Primary_Cells Sigmoid_Colon Mobilized_CD34_Primary_Cells_Female Aorta MEP GMP Right_Ventricle CMP Left_Ventricle CD34.CD38. Right_Atrium Psoas_Muscle Ovary Spleen Thymus Adult_Liver K562 GM12878 Erythroid BCell 1 Monocyte CD8_Naive_Primary_Cells CD4_Naive_Primary_Cells CD4_Memory_Primary_Cells TCell2 TCell1 Peripheral_Blood_Mononuclear_Primary_Cells Mobilized_CD34_Primary_Cells_Female MEP GMP CMP CD34.CD38. CD34.CD38. CMP GMP MEP Mobilized_CD34_Primary_Cells_Female Peripheral_Blood_Mononuclear_Primary_Cells TCell1 TCell2 CD4_Memory_Primary_Cells CD4_Naive_Primary_Cells CD8_Naive_Primary_Cells Monocyte BCell Erythroid GM12878 K562 Adult_Liver Thymus Spleen Ovary Psoas_Muscle Right_Atrium Left_Ventricle Right_Ventricle Aorta Sigmoid_Colon Small_Intestine Esophagus Gastric Lung Fetal_Intestine_Large Fetal_Intestine_Small Pancreatic_Islets Pancreas Brain_Hippocampus_Middle Fetal_Brain_Female Brain_Germinal_Matrix Neurosphere_Cultured_Cells_Cortex_Derived Neurosphere_Cultured_Cells_Ganglionic_Eminence_Derived hESC_Derived_CD184+_Endoderm_Cultured_Cells H1_Derived_Neuronal_Progenitor_Cultured_Cells hESC_Derived_CD56+_Ectoderm_Cultured_Cells H1_Cell_Line 4star H1_BMP4_Derived_Mesendoderm_Cultured_Cells HUES64_Cell_Line H1_BMP4_Derived_Trophoblast_Cultured_Cells hESC_Derived_CD56+_Mesoderm_Cultured_Cells HEPG2 A549 HELA Breast_Myoepithelial_Cells Penis_Foreskin_Keratinocyte_Primary_Cells_skin02 Penis_Foreskin_Keratinocyte_Primary_Cells_skin03 HMEC Breast_vHMEC NHEK Universal_Human_Reference HSMM NHLF H1_Derived_Mesenchymal_Stem_Cells Penis_Foreskin_Fibroblast_Primary_Cells_skin01 Penis_Foreskin_Fibroblast_Primary_Cells_skin02 HUVEC Penis_Foreskin_Melanocyte_Primary_Cells_skin01 Penis_Foreskin_Melanocyte_Primary_Cells_skin03 Figure S1. Related to Figure 1. Sorting strategy for hematopoietic populations profiled in this study. A) Representative examples of sorting strategies for CD34+CD38-, CMP, GMP, MEP, monocyte, erythroid precursors and B cell isolated from pool of cord blood. B) Unsupervised hierarchical clustering and heatmap of pairwise spearman correlations for protein coding gene RPKM values across blood cell types profiled in this study in the context of all cell types profiled by NIH Epigenome RoadMap Consortium. The cluster of blood cell types is indicated by the shaded box. 2 A CD14 CD19 CD34 C 250 150 200 60 150 100 40 100 20 50 50 D 0 0 0 CD38 CD7 FLT3 CD34.CD38. 60 CMP GMP 60 40 100 MEP 40 Monocyte Erythroid 1.00 RPKM RPKM 20 50 E 20 BCell TCell1 0 0 0 3 GYPA ITGAM PTPRC black 1.00 2000 80 300 1500 60 1000 40 200 F 500 20 100 0 2 0 0 B G H Log10(q-value) 0.75 TAL1 3 3 Mark 22 H3K27me3 1 Mark H3K36me3 H3K27me3 1 1 H3K36me3 H3K4me3 log10(RPKM) H3K4me3 0.75 log10(RPKM) 00 Log10(RPKM) Cell -1-1 - CMP MEP GMP B-Cell T-Cell H1 Monocyte Erythroid 0 CD34+CD38- CMP GMP MEP T Cell MPO B Cell CD34+CD38− MonocyteErythroid CD34+CD38 CMP Cell GMP 0.50 Cella$n Cell H1 MEP CB CD34+ CD38- MPL 1 CD34+CD38− -1CMP Monocyte TFRC 0.5 GMP CMP Erythroid VWF MEP GMP B−Cell 0 0.50 TAL1 Group CMP GMP MEP T-Cell a$n B-CellMEP T−Cell Erythroid/Megakaryocyte EPOR -0.5 Monocyte Erythroid Monocyte/Granulocyte Monocyte GATA1 -1 CD34+CD38-CD34+CD38- Compartment Erythroid GATA3 B−Cell HOXB5 T−Cell ID2 NR4A20.25 IL3RA 3 ELANE CSF2RA CEBPA 0.25 MPO CD33 SPI1 Group 0.00 H1 CD34+CD38− CMP GMP MEP Monocyte Erythroid B−Cell T−Cell a$Cell 0.00 H1 CD34+CD38− CMP GMP MEP Monocyte Erythroid B−Cell T−Cell a$Cell Figure S2. Related to Figure 1. Each progenitor populations possesses a unique expression profile. A) Expression (RPKM) of cell type specific cell surface marker genes across cell types as indicated by the colour legend on the bottom right. B) Expression of previously identified progenitor population specific genes across CD34+CD38-, CMP, GMP and MEP. Gene ontology analysis of GMP (C), MEP (D), CD34+CD38- (E), and CMP (F) up-regulated genes identified by DEFine (FDR > 0.01). G) Genome browser view of H3K4me3 density in progenitor populations at the TAL1 and MPO locus across CD34+CD38-, CMP, GMP and MEP. H) Expression of genes marked with H3K4me3, H3K27me3 or H3K36me3 across each cell type. 4 a$Cell Cell − T Cell − B Erythroid Monocyte MEP GMP CMP − CD34+CD38 H1 ✱✱✱ 0.00 DMSO Control ✱✱✱ DMSO Control ✱✱✱ DMSO Control A GMP vs Erythroid GMP vs MEP GMP vs MEP✱✱✱ MEP vs Monocyte ATRA ✱✱✱✱✱✱ DMSOATRA Control ✱✱✱ ATRA 4 ✱✱✱ ✱✱✱ GMP up-regulated GMP up-regulated MEP up-regulated MEP 4up-regulated ✱✱✱ GSK-J4 4 ✱✱✱✱✱✱ ✱✱✱ ATRA GSK-J4 ✱✱✱ ✱✱✱ GSK-J4 ✱✱✱ ✱✱✱ DMSO Control✱✱✱ DMSO Control ✱✱✱ ✱✱✱ 300 4 ✱✱✱ ✱✱✱ ns ✱✱✱ EPZ ✱✱✱ns ✱✱✱ ✱✱✱ ATRA GSK-J4EPZ ATRA ns ✱✱✱ EPZ 4 ✱✱✱ ✱✱✱ DMSO Control ✱✱✱ 4 ✱✱✱ ✱✱✱ ✱✱✱ GSK-J4✱✱✱✱✱✱ GSK-J4 ✱✱✱ CMP ATRA + GSK-J4 ✱✱✱ ✱✱✱ ✱✱✱ DMSO Control ✱✱✱ DMSO Control ns ✱✱✱ ✱✱✱ ✱✱✱EPZ✱✱✱✱✱✱ DMSO ControlATRA✱✱✱ ✱✱✱ ATRA + GSK-J4 ns ✱✱✱ ns ✱✱✱EPZ ✱✱✱ ATRA EPZ + GSK-J4 ✱✱✱ ✱✱✱ ✱✱✱ 4✱✱✱ ATRA ✱✱✱✱✱✱ GMP DMSO ControlATRA✱✱✱ 200 ✱✱✱ ✱✱✱ ✱✱✱ ✱✱✱3 ✱✱✱ DMSO Control ✱✱✱ ns ATRA GSK-J4 ATRA + EPZ ✱✱✱ ✱✱✱ ATRA✱✱✱ + GSK-J4 ATRA + GSK-J4ATRA + GSK-J4 ✱✱✱4 ✱✱✱ 4 ✱✱✱✱✱✱ ✱✱✱ 4 ATRA✱✱✱ +GSK-J4 EPZ 3 ✱✱✱ ✱✱✱✱✱ ns ATRA GSK-J4 ATRA + EPZ ✱✱✱3 ✱✱✱ ns✱✱✱✱✱✱ ✱✱✱ ✱✱✱✱✱✱✱✱✱ns ATRA ✱✱✱ GSK-J4EPZ MEP ✱✱✱ 3 ATRA + EPZ ATRA + EPZ 4 ✱✱✱ ✱✱✱ ✱✱✱ 3 ns ns ✱✱ns✱✱✱ ✱✱✱EPZ ✱✱✱ ns ✱✱✱ GSK-J4EPZ✱✱ 3 ns 4 ✱✱✱✱✱ ✱✱✱ ns✱✱✱✱✱ATRA +GSK-J4 EPZ ✱✱✱ ✱✱✱ EPZ ATRA + GSK-J4 ✱✱✱ ✱✱✱ ✱✱✱ ✱✱✱ ✱✱✱ns✱✱✱ ✱✱✱ Monocyte EPZ ✱✱ ✱✱✱✱✱✱ ✱✱✱ATRA + GSK-J4 ✱✱✱ ✱✱✱✱✱✱ ATRA + GSK-J4 100 ✱✱✱ ✱✱✱ns ✱✱✱ ✱✱✱ 3✱✱✱ EPZ ns ✱✱✱ ATRA +✱✱✱ ATRAGSK-J4 + EPZ ✱✱✱ ✱✱✱ ✱✱✱✱✱✱✱✱✱ ✱✱✱ ✱✱✱ Erythroid ATRA +✱✱✱ GSK-J4 3 ✱✱✱ns ATRA + EPZ ✱✱✱3✱✱ ATRA + EPZ ns ATRA + EPZ ✱✱✱ ✱✱✱ 3 ATRAns + GSK-J4 ✱✱✱ ✱✱ H3K4em3 tag density tag H3K4em3 ✱✱ ✱✱✱2 ✱✱✱ ✱✱✱ 3✱✱ ns ATRA + EPZ 2 ✱✱✱ 2 ATRA + EPZ ✱✱✱ 3 ns ✱✱✱ ✱✱✱ ✱✱✱ ✱✱ Normalized H3K4me3 tags H3K4me3 Normalized ✱✱ ✱✱✱ 2 ✱✱✱ 0 2 ✱✱✱ ✱✱✱ ✱✱✱ 2 ✱✱✱ 2 2 ✱✱✱ 2 B GMP vs Erythroid GMP vs MEP 2 GMP vs MEP MEP vs Monocyte 1 1 2 CMP GMP MEP CMP2 GMP MEP CMP GMP MEP CMP GMP MEP GMP up-regulated GMP up-regulated MEP up-regulated MEP up-regulated MonocyteErythroid MonocyteErythroid 1 MonocyteErythroid MonocyteErythroid ✱✱✱ 1 ✱✱✱ DMSO Control DMSO Control 1 1 1 1 ✱✱✱ DMSO Control ✱✱✱ DMSO Control 0 ✱✱✱ 0 ✱✱✱✱✱✱✱✱✱ ✱✱✱✱✱✱ ATRADMSO Control 1 DMSO✱✱✱✱✱✱ ControlATRA DMSO ControlDMSO Control ✱✱✱✱✱✱ 1 4 3 days ATRA 6 days 4 9DMSO days✱✱✱ Control ✱✱✱ DMSO Control 1 3 days 6 days 9 days✱✱✱ DMSO ✱✱✱Control ✱✱✱ ATRAGSK-J4 0.25 CMP ✱✱✱ ATRAGSK-J4 ✱✱✱✱✱✱ ATRA 4 ✱✱✱ ✱✱✱ GSK-J4 4 ✱✱✱ ✱✱✱ ✱✱✱ DMSO Control ✱✱✱ 4 ✱✱✱✱✱✱ ATRA✱✱✱✱✱✱ 0 ✱✱✱✱✱✱ns ✱✱✱ 4 ATRA EPZ GSK-J4✱✱✱ 40 ✱✱✱ ✱✱✱ns ATRA EPZ GSK-J4 ✱✱✱✱✱✱✱✱✱✱✱✱ GMP ATRA GSK-J4 ATRA 4 ns ✱✱✱✱✱✱ 0 EPZ 0 ✱✱✱✱✱✱ 3 days 6 days 0 9 days✱✱✱ ✱✱✱ ATRA ✱✱✱ GSK-J4✱✱✱ ns ✱✱✱✱✱✱ ATRAEPZ + GSK-J4 4 4 ✱✱✱✱✱✱ns3 days ✱✱✱6 days✱✱✱4 9 days ATRAEPZ + GSK-J4✱✱✱40 ✱✱✱ns3 days ✱✱✱6 days 9 days EPZ 1.00 ✱✱✱ ✱✱✱✱✱✱ ✱✱✱ ✱✱✱✱✱✱ ATRA + GSK-J4 ✱✱✱3 ✱✱✱days ✱✱✱GSK-J4 6 days 9 days4✱✱✱ GSK-J4✱✱✱ ✱✱✱ ✱✱✱MEP ✱✱✱ GSK-J4 GSK-J4 GSK-J4 ✱✱✱ns 0 EPZ 03 ATRA✱✱✱ + EPZ 3 days 6 ATRAdays + + EPZ GSK-J4 9 days ✱✱✱ 3✱✱✱✱✱✱ ✱✱✱✱✱✱ns ✱✱✱ ✱✱✱ATRAns− + GSK-J4 ✱✱✱ ✱✱✱✱✱✱ ✱✱✱ATRA + GSK-J4 3 days✱✱✱ 6ATRA days + EPZ 9 days✱✱✱✱✱ 0✱✱✱✱✱ns ✱✱✱ ✱✱✱ EPZ 03 ✱✱✱ns ✱✱✱ ns ATRA + GSK-J4✱✱✱ 3ns 3 days ns ✱✱✱ 6 daysEPZ ATRA +9 EPZ days✱✱✱Monocyte✱✱✱EPZ