Models of human hematopoietic hierarchy. Representation of classical and revised models for HSC differentiation toward mature lineages based on recent literature.22-25 We reported in black the name of hematopoietic populations, whereas in dark red, the differentiation-driving genes. HSCs and MPPs shared similar HOXB6/HOXA2/PRDM16 gene modules but different metabolic state. HSC characteristics are listed on top left (in red), whereas MPP state is associated with activation of mechanisms listed on top right (orange). In the HSC/MPP cloud, preexisting lineage-specific modules are present at low levels and reinforced along differentiation: NEF2/GATA2 module represents the first attraction point for the megakaryocytic/erythroid specification, whereas CBPE/STAT1/TCF4 is associated with lymphoid-myeloid primed progenitor (LMPP) specification. Interestingly, dendritic cell (DC) and multilymphoid progenitor (MLP) cell fates appear to be associated with STAT1 expression, but IRF8 and ID3/TCF4 modules drive their final specification, respectively. The link between MLP and DC is in line with previous publications.9 B, B cells, CMP, common myeloid progenitors; E, erythrocytes; ETP, early T-cell progenitors; GMP, granulocytes monocytes progenitors; M, Monocytes; MEP, megakaryocytes erythrocytes progenitors; MK, megakaryocytes; NK, natural killer cells; PMN, polymorphonucleated cells; PreB/NK, B-cell and NK cell progenitors; T, T cells.