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bioRxiv · 10.64898/2026.04.09.711986

Cellular hydraulics ensures robust endothelial-to-haematopoietic transition

Kondrychyn, I.·Chen, Y.·Kumar, R.·Chen, G.·Kawakami, K.·McEvoy, E.·Phng, L.-K.
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Abstract

Haematopoietic stem and progenitor cells (HSPCs) emerge from specialised haemogenic endothelial cells (HECs) in the ventral wall of the dorsal aorta (VDA) through a process known as endothelial-to-haematopoietic transition (EHT). During EHT, elongated HECs undergo actomyosin-driven rounding and extrusion, a mechanically demanding transformation that requires cell integrity to be maintained. Here, we identify an osmo-hydraulic volume-regulation mechanism that enables HECs to adapt to and withstand this mechanical challenge. Haemodynamic forces increase Piezo-dependent calcium ion activity in ventral endothelial cells, while Piezo activation promotes HEC swelling. Combined genetic and pharmacological analyses support a pathway in which Piezo-mediated swelling triggers VRAC-dependent osmolyte efflux and Aqp1a.1-mediated water efflux to reduce HEC volume. Disrupting either osmolyte or water efflux causes excessive HEC swelling, compromises HEC integrity and reduces HSPC production. Together, our findings establish osmo-hydraulic volume regulation as a mechanism that preserves cellular robustness during EHT and support a model in which aquaporins act as pressure-relief valves, dissipating intracellular hydrostatic pressure to sustain HEC survival and definitive haematopoiesis.

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Kondrychyn, I., Chen, Y., Kumar, R., Chen, G., Kawakami, K., McEvoy, E., Phng, L.-K.. 2026-04-13. Cellular hydraulics ensures robust endothelial-to-haematopoietic transition. https://doi.org/10.64898/2026.04.09.711986

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