Endothelial-to-hematopoietic transition (EHT) is crucial for hematopoietic stem cell (HSC) generation. During EHT, hemogenic endothelial cells (HECs) change from flat to round-shaped and detach from the endothelium to enter the blood stream. It remains unclear what drives this cell morphological change. Previous studies show that water influx through aquaporin channels promotes migration of vascular endothelial cells and other cell types. Here, Yuki Sato and colleagues uncover a role for aquaporins in regulating cell rounding and detachment of emerging HSCs through vacuole formation. First, the authors use light and electron microscopy to show that large vacuoles are transiently formed in HECs of avian embryos, and that aquaporin 1 (AQP1) are localised in the vacuoles. Then, they overexpress AQP1 in non-HECs and observe cell morphological changes that mimic what happens to HECs during EHT. Finally, by removing the function of several AQP genes in HECs via CRISPR/Cas9 gene editing, the authors find that AQP channels are redundantly required for HEC rounding and that EHT is impaired in these mutants. Overall, this work provides evidence that the morphological changes of HSCs from endothelial cells during EHT is regulated by water influx into vacuoles through aquaporins.
