. 2023 Feb 20;142(6):519–532. doi: 10.1182/blood.2022017934

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, 22, 23, 24, 25, 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, 26, 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, 29, 30, 31

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