Figure 7.

ERG is required to sustain definitive hematopoiesis. During early embryonic hematopoietic development, ERG is not required for hematopoietic specification from the mesoderm; thus, Erg^Mld2/Mld2 cells can undergo primitive erythropoiesis, progenitor formation, and HSC emergence (pre-HSC-to-HSC transition). These developmental pathways require a first wave of Gata2 and Runx1 expression; this is not dependent on ERG. Once definitive hematopoiesis is initiated, HSCs are required to execute maintaining self-renewals to preserve their numbers while contributing to hematopoiesis. At this point, ERG is critical and acts by controlling a second wave of Gata2 and Runx1 gene activity. In the absence of ERG (as in the case of the Erg^Mld2 embryo), HSCs are capable of contributing to hematopoiesis, but maintaining self-renewals are dysfunctional; thus, hematopoietic contribution is transient due to rapid HSC exhaustion.