Endothelial-specific Gata3 expression is required for hematopoietic stem cell generation

To generate sufficient numbers of transplantable hematopoietic stem cells (HSCs) in vitro, a detailed understanding of how this process takes place in vivo is essential. The endothelial-to-hematopoietic transition (EHT), which culminates in the production of the first HSCs, is a highly complex process during which key regulators are switched on and off at precise moments, and that is embedded into a myriad of microenvironmental signals from surrounding cells and tissues. We have previously demonstrated an HSC-supportive function for GATA3 within the sympathetic nervous system and the sub-aortic mesenchyme, but show here that it also plays a cell-intrinsic role during the EHT. It is expressed in hemogenic endothelial cells and early HSC precursors, where its expression correlates with a more quiescent state. Importantly, endothelial-specific deletion of Gata3 shows that it is functionally required for these cells to mature into HSCs, placing GATA3 at the core of the EHT regulatory network.

Automated summary

To generate sufficient numbers of transplantable hematopoietic stem cells (HSCs) in vitro, a detailed understanding of the complex process of endothelial-to-hematopoietic transition (EHT), which involves key regulators and microenvironmental signals, is essential. This study reveals that GATA3 plays a crucial cell-intrinsic role in the EHT process, as its expression in hemogenic endothelial cells and early HSC precursors is correlated with a more quiescent state. Endothelial-specific deletion of Gata3 shows that it is functionally required for these cells to mature into HSCs, highlighting the importance of GATA3 in the regulatory network of EHT.