Ribosome biogenesis is required in hemogenic endothelial cells to generate hematopoietic stem cells

Undergoing endothelial-to-hematopoietic transition, a small fraction of embryonic aortic endothelial cells specializes into hemogenic endothelial cells (HECs) and eventually gives rise to hematopoietic stem cells (HSCs). Previously we have found that the activity of ribosome biogenesis (RiBi) is highly enriched in the HSC-primed HECs as compared with adjacent arterial endothelial cells, however, whether RiBi is required in HECs for the generation of HSC remain to be determined. Here, we found that robust RiBi was markedly augmented from HEC stage along the HSC ontogeny. Pharmacological inhibition of RiBi completely impeded the generation of HSCs in explant cultures. Moreover, disrupting RiBi selectively interrupted the HSC generation potential of HECs rather than T1 pre-HSCs, which was in line with its influence on cell cycle activity. Further investigation revealed that upon HEC specification the master transcription factor Runx1 dramatically bound to the loci of genes involved in RiBi, thereby facilitating this biological process. Taken together, our study provided functional evidence showing the indispensable role of RiBi in HSC-primed HECs to generate HSCs, providing novel insights that may contribute to improving HSC regeneration strategies.