During embryogenesis of all vertebrates, haematopoietic stem/progenitor cells (HSPCs) extrude from the aorta by a complex process named endothelial-to-haematopoietic transition (EHT). HSPCs will then colonize haematopoietic organs allowing haematopoiesis throughout adult life. The mechanism underlying EHT including the role of each aortic endothelial cell (EC) within the global aorta dynamics remains unknown. In the present study, we show for the first time that EHT involves the remodelling of individual cells within a collective migration of ECs which is tightly orchestrated, resulting in HSPCs extrusion in the sub-aortic space without compromising aorta integrity. By performing a cross-disciplinary study which combines high-resolution 4D imaging and theoretical analysis based on the concepts of classical mechanics, we propose that this complex developmental process is dependent on mechanical instabilities of the aorta preparing and facilitating the extrusion of HSPCs.
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We thank Etienne Lelièvre for his critical reading of the manuscript, A. Sahuquet, C. Chevalier, V. Diakou for their assistance and the MRI facility, N. Abdellaoui for management of zebrafish facility. D. Stainier lab for Tg(Cdh5:Gal4//UAS:lifeact:GFP), S. Shulte-Merker lab for Tg(kdrl:utrophin-CH-GFP) and Tg(kdrl:nls-GFP) and National Bioresource Project Zebrafish for Tg(flk-1:mV-zGem). This work was supported by the ARC, FRM, ATIP-Avenir fellowships and a fellowship from the Région Languedoc-Roussillon, Chercheur d’Avenir. NP was supported by a fellowship from the ATIP-Avenir, SR and DC are grateful to the RFBR Grant N 18-29-19043, AP, IG, DC and SR acknowledge the LabEx NUMEV (AAP-2016-2-025) for financial support. I.G.’s thesis was funded by Campus France (Vernadsky Fellowship) and the France–Russia Cooperation Program, and JT by a fellowship from the MESR and the FRM.
Conflict of interest
The authors declare no competing financial interests.
We dedicate this work to the memory of our friend and colleague, V. Lorman.
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Poullet, N., Golushko, I., Lorman, V. et al. Mechanical instabilities of aorta drive blood stem cell production: a live study. Cell. Mol. Life Sci. 77, 3453–3464 (2020). https://doi.org/10.1007/s00018-019-03372-2
- Endothelial-to-haematopoietic transition
- 4D microscopy