Putative key regulators of primitive erythropoiesis are differential expressed in primitive versus adult definitive erythropoiesis. 144 genes in the right-tail of the distribution of estimated essentiality scores for the primitive erythroid lineage were found to be differentially expressed compared to the adult definitive erythroid lineage. These genes fall into 6 clusters: A) primitive: preferentially expressed late, definitive: steady-state expression at low levels or not expressed; B) primitive: steady-state expression at low levels or not expressed, definitive: preferentially expressed late; C) preferentially expressed in primitive proerythroblasts; D) primitive: preferentially expressed early and not expressed late, definitive: expression at low levels with some preferential expression in proerythroblasts; E) primitive: preferentially expressed early and not expressed late, definitive: preferentially expressed early and expressed late; and F) primitive: preferential expression early at low levels or not expressed, definitive: preferential expression early or high-levels of steady-state expression. Gene set enrichment analysis identified 56 genes activated downstream of MAPK signaling (†), 11 of which also are downstream effectors of EPO-induced signaling pathways (red). A high-quality version of this image with the heatmap assembled into a single column and cluster dendrogram is available in the Additional file 4: Figure S7.