Mechanical instabilities of aorta drive blood stem cell production: a live study
Abstract
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.
Keywords
Haematopoiesis Zebrafish Endothelial-to-haematopoietic transition 4D microscopy ModelingNotes
Acknowledgements
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.
Compliance with ethical standards
Conflict of interest
The authors declare no competing financial interests.
Supplementary material
References
- 1.Lis R et al (2017) Conversion of adult endothelium to immunocompetent haematopoietic stem cells. Nature 545:439–445CrossRefGoogle Scholar
- 2.Batta K, Florkowska M, Kouskoff V, Lacaud G (2014) Direct reprogramming of murine fibroblasts to hematopoietic progenitor cells. Cell Rep 9:1871–1884CrossRefGoogle Scholar
- 3.Riddell J et al (2014) Reprogramming committed murine blood cells to induced hematopoietic stem cells with defined factors. Cell 157:549–564CrossRefGoogle Scholar
- 4.Lancrin C et al (2009) The haemangioblast generates haematopoietic cells through a haemogenic endothelium stage. Nature 457:892–895CrossRefGoogle Scholar
- 5.Ivanovs A et al (2017) Human haematopoietic stem cell development: from the embryo to the dish. Development 144:2323–2337CrossRefGoogle Scholar
- 6.Hamill OP, Martinac B (2001) Molecular basis of mechanotransduction in living cells. Physiol Rev 81:685–740CrossRefGoogle Scholar
- 7.Eyckmans J, Boudou T, Yu X, Chen CS (2011) A Hitchhiker’s guide to mechanobiology. Dev Cell 21:35–47CrossRefGoogle Scholar
- 8.Modesto K, Sengupta PP (2014) Myocardial mechanics in cardiomyopathies. Prog Cardiovasc Dis 57:111–124CrossRefGoogle Scholar
- 9.Desprat N, Supatto W, Pouille P-A, Beaurepaire E, Farge E (2008) Tissue deformation modulates twist expression to determine anterior midgut differentiation in drosophila embryos. Dev Cell 15:470–477CrossRefGoogle Scholar
- 10.Gering M, Patient R (2005) Hedgehog signaling is required for adult blood stem cell formation in zebrafish embryos. Dev Cell 8:389–400CrossRefGoogle Scholar
- 11.Tavian M, Péault B (2005) Embryonic development of the human hematopoietic system. Int J Dev Biol 49:243–250CrossRefGoogle Scholar
- 12.Murayama E et al (2006) Tracing hematopoietic precursor migration to successive hematopoietic organs during zebrafish development. Immunity 25:963–975CrossRefGoogle Scholar
- 13.Kissa K et al (2008) Live imaging of emerging hematopoietic stem cells and early thymus colonization. Blood 111:1147–1156CrossRefGoogle Scholar
- 14.Kissa K, Herbomel P (2010) Blood stem cells emerge from aortic endothelium by a novel type of cell transition. Nature 464:112–115CrossRefGoogle Scholar
- 15.Bertrand JY et al (2010) Haematopoietic stem cells derive directly from aortic endothelium during development. Nature 464:108–111CrossRefGoogle Scholar
- 16.Robin C et al (2009) Human placenta is a potent hematopoietic niche containing hematopoietic stem and progenitor cells throughout development. Cell Stem Cell 5:385–395CrossRefGoogle Scholar
- 17.Kimmel CB, Ballard WW, Kimmel SR, Ullmann B, Schilling TF (1995) Stages of embryonic development of the zebrafish. Dev Dyn 203:253–310CrossRefGoogle Scholar
- 18.Chen MJ, Yokomizo T, Zeigler BM, Dzierzak E, Speck NA (2009) Runx1 is required for the endothelial to haematopoietic cell transition but not thereafter. Nature 457:887–891CrossRefGoogle Scholar
- 19.Lancino M et al (2018) Anisotropic organization of circumferential actomyosin characterizes hematopoietic stem cells emergence in the zebrafish. Elife 7:1–36CrossRefGoogle Scholar
- 20.Fukuhara S et al (2014) Visualizing the cell-cycle progression of endothelial cells in zebrafish. Dev Biol 393:10–23CrossRefGoogle Scholar
- 21.Burkel BM, von Dassow G, Bement WM (2007) Versatile fluorescent probes for actin filaments based on the actin-binding domain of utrophin. Cell Motil Cytoskelet 64:822–832CrossRefGoogle Scholar
- 22.Helker CSM et al (2013) The zebrafish common cardinal veins develop by a novel mechanism: lumen ensheathment. Development 140:2776–2786CrossRefGoogle Scholar
- 23.Lin H-F et al (2005) Analysis of thrombocyte development in CD41-GFP transgenic zebrafish. Blood 106:3803–3810CrossRefGoogle Scholar
- 24.Golushko IY, Rochal SB, Lorman VL (2015) Complex instability of axially compressed tubular lipid membrane with controlled spontaneous curvature. Eur Phys J E 38:112CrossRefGoogle Scholar
- 25.Alstrøm P, Eguíluz VM, Colding-Jørgensen M, Gustafsson F, Holstein-Rathlou N-H (1999) Instability and “Sausage-String” appearance in blood vessels during high blood pressure. Phys Rev Lett 82:1995–1998CrossRefGoogle Scholar
- 26.Li B, Cao Y-P, Feng X-Q, Gao H (2011) Surface wrinkling of mucosa induced by volumetric growth: theory, simulation and experiment. J Mech Phys Solids 59:758–774CrossRefGoogle Scholar
- 27.Muñoz MA (2018) Colloquium: criticality and dynamical scaling in living systems. Rev Mod Phys 90:031001CrossRefGoogle Scholar
- 28.Santoro MM, Pesce G, Stainier DY (2009) Characterization of vascular mural cells during zebrafish development. Mech Dev 126:638–649CrossRefGoogle Scholar
- 29.Campàs O (2016) A toolbox to explore the mechanics of living embryonic tissues. Semin Cell Dev Biol 55:119–130CrossRefGoogle Scholar
- 30.Wyatt T, Baum B, Charras G (2016) A question of time: tissue adaptation to mechanical forces. Curr Opin Cell Biol 38:68–73CrossRefGoogle Scholar
- 31.Landau LD, Lifshitz EM (1980) Statistical physics, part 1. In: Sykes JB, Kearsley MJ (eds) Theoretical physics, vol 5. Butterworth-Heinemann, OxfordGoogle Scholar
- 32.Timoshenko S, Goodier JN (1951) Theory of elasticity. McGraw-Hill Book Company Inc., New YorkGoogle Scholar
- 33.Guillot C, Lecuit T (2013) Mechanics of epithelial tissue homeostasis and morphogenesis. Science (80-.) 340:1185–1189CrossRefGoogle Scholar
- 34.Rosenblatt J, Raff MC, Cramer LP (2001) An epithelial cell destined for apoptosis signals its neighbors to extrude it by an actin- and myosin-dependent mechanism. Curr Biol 11:1847–1857CrossRefGoogle Scholar
- 35.Bi D, Yang X, Marchetti MC, Manning ML (2016) Motility-driven glass and jamming transitions in biological tissues. Phys Rev X 6:021011PubMedPubMedCentralGoogle Scholar
- 36.Farhadifar R, Röper J-C, Aigouy B, Eaton S, Jülicher F (2007) The influence of cell mechanics, cell-cell interactions, and proliferation on epithelial packing. Curr Biol 17:2095–2104CrossRefGoogle Scholar
- 37.Merkel M et al (2017) Triangles bridge the scales: quantifying cellular contributions to tissue deformation. Phys Rev E 95:032401CrossRefGoogle Scholar
- 38.Krajnc M, Dasgupta S, Ziherl P, Prost J (2018) Fluidization of epithelial sheets by active cell rearrangements. Phys Rev E. https://doi.org/10.1103/PhysRevE.98.022409 CrossRefPubMedGoogle Scholar
- 39.Chi NC et al (2008) Foxn4 directly regulates tbx2b expression and atrioventricular canal formation. Genes Dev 22:734–739CrossRefGoogle Scholar
- 40.Blum Y et al (2008) Complex cell rearrangements during intersegmental vessel sprouting and vessel fusion in the zebrafish embryo. Dev Biol 316:312–322CrossRefGoogle Scholar
- 41.Westerfield M (2000) The zebrafish book. A guide for the laboratory use of zebrafish (Danio rerio), 4th edn. Univ. of Oregon Press, EugeneGoogle Scholar
- 42.Renaud O, Herbomel P, Kissa K (2011) Studying cell behavior in whole zebrafish embryos by confocal live imaging: application to hematopoietic stem cells. Nat Protoc 6:1897–1904CrossRefGoogle Scholar