Table 1. Human HSC ontogeny and... | American Society of Hematology

Table 1.

Human HSC ontogeny and characteristics

Human hematopoietic cell type	Description and functional properties	RNA expression signature	Protein markers	References
HSC endothelial precursors
AGM AE CS13/15 wk 4 to wk 5	Arterial ECs from the AGM region lining the aorta	RUNX1^–HOXA9⁺MEIS2⁺SOX17⁺	CDH5⁺CD34⁺CD90⁺CXCR4⁺GJA5⁺ CD43^–CD45^–	15,16
AGM pre-HE CS13/15 wk 4 to wk 5	Subset of AE cells from the aorta preceding the activation of hematopoietic transition	RUNX1^–HOXA9⁺MEIS2⁺SOX17⁺IL-33⁺ ALDH1A1⁺DKK1⁺	CDH5⁺CD34⁺CD90⁺CXCR4⁺GJA5⁺IL-33⁺ALDH1A1⁺CD43^–CD45^–	15
AGM HE CS13/15 wk 4 to wk 5	Subset of AE on the ventral side of dorsal aorta undergoing EHT (RUNX1 expression without SPN/PTPRC activation)	RUNX1⁺HOXA9⁺MEIS2⁺SOX17⁺ALDH1A1⁺ DKK1⁺	CDH5⁺CD34⁺CD90⁺CD44⁺ KCNK17⁺CD43^–CD45^–	15,16
HSC
AGM HSCs CS14/15 wk 4 to wk 5	HSC emerging via IAHC, undifferentiated state with immature endothelial/megakaryocytic surface features and displaying functional immaturity. Rare highly potent transplantable HSCs.	RUNX1⁺MLLT3⁺HOXA9⁺SPINK2⁺HLF⁺MECOM⁺LIN28B⁺IGFBP2⁺HOXB9⁺	CD34⁺CD90⁺KCNK17⁺CD43⁺CD45⁺ CDH5⁺EMCN⁺ACE⁺PROCR⁺	15,17,18
Yolk sac HSCs CS14/CS16	HSCs displaying functional immaturity but diminished endothelial features compared with AGM HSCs. Transplantable HSCs found at CS16. Erythroid priming and transcriptional similarity to CS17 liver HSCs observed.	RUNX1⁺MLLT3⁺HOXA9⁺SPINK2⁺HLF⁺MECOM⁺LIN28B⁺IGFBP2⁺HOXB9⁺	CD34⁺CD90⁺CD43⁺CD45⁺ CDH5^+/−ACE⁺PROCR⁺	15,17,19
Placental HSCs CS14 to wk 9	HSCs displaying functional immaturity but diminished endothelial features compared with AGM HSCs. Erythroid priming and transcriptional similarity to CS17 liver HSCs are observed. Presence of GPI80⁺ HSPCs observed at 5 wk.	RUNX1⁺MLLT3⁺HOXA9⁺SPINK2⁺HLF⁺MECOM⁺LIN28B⁺IGFBP2⁺HOXB9⁺	CD34⁺CD90⁺CD43⁺CD45⁺GPI80⁺ CDH5^+/−ACE⁺PROCR⁺	15,19,20
Embryonic liver HSC CS17/20 wk 6 to wk 7	HSC displaying functional immaturity but showing suppression of endothelial features. Erythro-megakaryocyte-myeloid differentiation-primed.	RUNX1⁺MLLT3⁺HOXA9⁺SPINK2⁺HLF⁺MECOM⁺IGFBP2⁺LIN28B⁺HOXB9⁺	CD34⁺CD90⁺CD43⁺CD45⁺GPI80⁺ ACE⁺PROCR⁺	15,17,19
First trimester fetal liver HSC from wk 8 to wk 12	Transplantable HSCs, progressive decline of fetal programs, gradual acquisition of multipotency and quiescence, and increased expression of MHC class I and II and PROM1	RUNX1⁺MLLT3⁺HOXA9⁺SPINK2⁺HLF⁺MECOM⁺HEMGN	CD34⁺CD90⁺CD43⁺CD45⁺GPI80⁺ACE⁺PROCR⁺PROM1⁺HLA-DR⁺	15,19,21
Second trimester liver HSCs from wk 13 to wk 20	Transplantable HSCs, gradual loss of fetal properties and transition to quiescence, and robust expression of MHC class I and II and PROM1	RUNX1⁺MLLT3⁺HOXA9⁺SPINK2⁺HLF⁺MECOM⁺HEMGN⁺MSI2^hi+	CD34⁺CD90⁺CD43⁺CD45⁺GPI80⁺ACE⁺PROCR⁺PROM1⁺HLA-DR⁺	15,21-26
Second trimester fetal BM HSCs	Transplantable HSCs, further transition to quiescence, and robust expression of MHC class I and II and PROM1	RUNX1⁺MLLT3⁺HOXA9⁺SPINK2⁺HLF⁺MECOM⁺HEMGN⁺MSI2^hi	CD34⁺CD90⁺CD43⁺CD45⁺GPI80⁺ACE⁺PROCR⁺PROM1⁺HLA-DR⁺	20,23,25-27
Cord blood HSCs	Transplantable HSCs, complete acquisition of functional maturation signature, and robust expression of MHC class I and II	RUNX1⁺MLLT3⁺HOXA9⁺SPINK2⁺ HLF⁺MECOM⁺HEMGN⁺MSI2^hi	CD34⁺CD90⁺CD43⁺CD45⁺GPI80^–ACE⁺ PROCR⁺PROM1⁺HLA-DR⁺SELL⁺EMCN⁺ CD164⁺	15,28-31

Human hematopoietic cell type	Description and functional properties	RNA expression signature	Protein markers	References
HSC endothelial precursors
AGM AE CS13/15 wk 4 to wk 5	Arterial ECs from the AGM region lining the aorta	RUNX1^–HOXA9⁺MEIS2⁺SOX17⁺	CDH5⁺CD34⁺CD90⁺CXCR4⁺GJA5⁺ CD43^–CD45^–	15,16
AGM pre-HE CS13/15 wk 4 to wk 5	Subset of AE cells from the aorta preceding the activation of hematopoietic transition	RUNX1^–HOXA9⁺MEIS2⁺SOX17⁺IL-33⁺ ALDH1A1⁺DKK1⁺	CDH5⁺CD34⁺CD90⁺CXCR4⁺GJA5⁺IL-33⁺ALDH1A1⁺CD43^–CD45^–	15
AGM HE CS13/15 wk 4 to wk 5	Subset of AE on the ventral side of dorsal aorta undergoing EHT (RUNX1 expression without SPN/PTPRC activation)	RUNX1⁺HOXA9⁺MEIS2⁺SOX17⁺ALDH1A1⁺ DKK1⁺	CDH5⁺CD34⁺CD90⁺CD44⁺ KCNK17⁺CD43^–CD45^–	15,16
HSC
AGM HSCs CS14/15 wk 4 to wk 5	HSC emerging via IAHC, undifferentiated state with immature endothelial/megakaryocytic surface features and displaying functional immaturity. Rare highly potent transplantable HSCs.	RUNX1⁺MLLT3⁺HOXA9⁺SPINK2⁺HLF⁺MECOM⁺LIN28B⁺IGFBP2⁺HOXB9⁺	CD34⁺CD90⁺KCNK17⁺CD43⁺CD45⁺ CDH5⁺EMCN⁺ACE⁺PROCR⁺	15,17,18
Yolk sac HSCs CS14/CS16	HSCs displaying functional immaturity but diminished endothelial features compared with AGM HSCs. Transplantable HSCs found at CS16. Erythroid priming and transcriptional similarity to CS17 liver HSCs observed.	RUNX1⁺MLLT3⁺HOXA9⁺SPINK2⁺HLF⁺MECOM⁺LIN28B⁺IGFBP2⁺HOXB9⁺	CD34⁺CD90⁺CD43⁺CD45⁺ CDH5^+/−ACE⁺PROCR⁺	15,17,19
Placental HSCs CS14 to wk 9	HSCs displaying functional immaturity but diminished endothelial features compared with AGM HSCs. Erythroid priming and transcriptional similarity to CS17 liver HSCs are observed. Presence of GPI80⁺ HSPCs observed at 5 wk.	RUNX1⁺MLLT3⁺HOXA9⁺SPINK2⁺HLF⁺MECOM⁺LIN28B⁺IGFBP2⁺HOXB9⁺	CD34⁺CD90⁺CD43⁺CD45⁺GPI80⁺ CDH5^+/−ACE⁺PROCR⁺	15,19,20
Embryonic liver HSC CS17/20 wk 6 to wk 7	HSC displaying functional immaturity but showing suppression of endothelial features. Erythro-megakaryocyte-myeloid differentiation-primed.	RUNX1⁺MLLT3⁺HOXA9⁺SPINK2⁺HLF⁺MECOM⁺IGFBP2⁺LIN28B⁺HOXB9⁺	CD34⁺CD90⁺CD43⁺CD45⁺GPI80⁺ ACE⁺PROCR⁺	15,17,19
First trimester fetal liver HSC from wk 8 to wk 12	Transplantable HSCs, progressive decline of fetal programs, gradual acquisition of multipotency and quiescence, and increased expression of MHC class I and II and PROM1	RUNX1⁺MLLT3⁺HOXA9⁺SPINK2⁺HLF⁺MECOM⁺HEMGN	CD34⁺CD90⁺CD43⁺CD45⁺GPI80⁺ACE⁺PROCR⁺PROM1⁺HLA-DR⁺	15,19,21
Second trimester liver HSCs from wk 13 to wk 20	Transplantable HSCs, gradual loss of fetal properties and transition to quiescence, and robust expression of MHC class I and II and PROM1	RUNX1⁺MLLT3⁺HOXA9⁺SPINK2⁺HLF⁺MECOM⁺HEMGN⁺MSI2^hi+	CD34⁺CD90⁺CD43⁺CD45⁺GPI80⁺ACE⁺PROCR⁺PROM1⁺HLA-DR⁺	15,21-26
Second trimester fetal BM HSCs	Transplantable HSCs, further transition to quiescence, and robust expression of MHC class I and II and PROM1	RUNX1⁺MLLT3⁺HOXA9⁺SPINK2⁺HLF⁺MECOM⁺HEMGN⁺MSI2^hi	CD34⁺CD90⁺CD43⁺CD45⁺GPI80⁺ACE⁺PROCR⁺PROM1⁺HLA-DR⁺	20,23,25-27
Cord blood HSCs	Transplantable HSCs, complete acquisition of functional maturation signature, and robust expression of MHC class I and II	RUNX1⁺MLLT3⁺HOXA9⁺SPINK2⁺ HLF⁺MECOM⁺HEMGN⁺MSI2^hi	CD34⁺CD90⁺CD43⁺CD45⁺GPI80^–ACE⁺ PROCR⁺PROM1⁺HLA-DR⁺SELL⁺EMCN⁺ CD164⁺	15,28-31

Characteristics of different human HSC endothelial precursors and HSC maturation stages.