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Background  Hematopoiesis is a progressive process collectively controlled by an elaborate network of transcription factors (TFs). Among these TFs, GATA2 has been implicated to be critical for regulating multiple steps of hematopoiesis in mouse models. However, whether similar function of GATA2 is conserved in human hematopoiesis, especially during early embryonic development stage, is largely unknown.    Results  To examine the role of GATA2 in human background, we generated homozygous  GATA2  knockout human embryonic stem cells ( GATA2    −/−   hESCs) and analyzed their blood differentiation potential. Our results demonstrated that  GATA2    −/−   hESCs displayed attenuated generation of CD34 + CD43 +  hematopoietic progenitor cells (HPCs), due to the impairment of endothelial to hematopoietic transition (EHT). Interestingly,  GATA2    −/−   hESCs retained the potential to generate erythroblasts and macrophages, but never granulocytes. We further identified that SPI1 downregulation was partially responsible for the defects of  GATA2    −/−   hESCs in generation of CD34 + CD43 +  HPCs and granulocytes. Furthermore, we found that  GATA2    −/−   hESCs restored the granulocyte potential in the presence of Notch signaling.    Conclusion  Our findings revealed the essential roles of GATA2 in EHT and granulocyte development through regulating  SPI1 , and uncovered a role of Notch signaling in granulocyte generation during hematopoiesis modeled by human ESCs.    Electronic supplementary material  The online version of this article (doi:10.1186/s13619-015-0018-7) contains supplementary material, which is available to authorized users.

GATA2 −/− human ESCs undergo attenuated endothelial to hematopoietic transition and thereafter granulocyte commitment