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.

This is a preview of subscription content, access via your institution.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

References

  1. 1.

    Lis R et al (2017) Conversion of adult endothelium to immunocompetent haematopoietic stem cells. Nature 545:439–445

    CAS  Article  Google Scholar 

  2. 2.

    Batta K, Florkowska M, Kouskoff V, Lacaud G (2014) Direct reprogramming of murine fibroblasts to hematopoietic progenitor cells. Cell Rep 9:1871–1884

    CAS  Article  Google Scholar 

  3. 3.

    Riddell J et al (2014) Reprogramming committed murine blood cells to induced hematopoietic stem cells with defined factors. Cell 157:549–564

    CAS  Article  Google Scholar 

  4. 4.

    Lancrin C et al (2009) The haemangioblast generates haematopoietic cells through a haemogenic endothelium stage. Nature 457:892–895

    CAS  Article  Google Scholar 

  5. 5.

    Ivanovs A et al (2017) Human haematopoietic stem cell development: from the embryo to the dish. Development 144:2323–2337

    CAS  Article  Google Scholar 

  6. 6.

    Hamill OP, Martinac B (2001) Molecular basis of mechanotransduction in living cells. Physiol Rev 81:685–740

    CAS  Article  Google Scholar 

  7. 7.

    Eyckmans J, Boudou T, Yu X, Chen CS (2011) A Hitchhiker’s guide to mechanobiology. Dev Cell 21:35–47

    CAS  Article  Google Scholar 

  8. 8.

    Modesto K, Sengupta PP (2014) Myocardial mechanics in cardiomyopathies. Prog Cardiovasc Dis 57:111–124

    Article  Google Scholar 

  9. 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 15:470–477

    CAS  Article  Google Scholar 

  10. 10.

    Gering M, Patient R (2005) Hedgehog signaling is required for adult blood stem cell formation in zebrafish embryos. Dev Cell 8:389–400

    CAS  Article  Google Scholar 

  11. 11.

    Tavian M, Péault B (2005) Embryonic development of the human hematopoietic system. Int J Dev Biol 49:243–250

    CAS  Article  Google Scholar 

  12. 12.

    Murayama E et al (2006) Tracing hematopoietic precursor migration to successive hematopoietic organs during zebrafish development. Immunity 25:963–975

    CAS  Article  Google Scholar 

  13. 13.

    Kissa K et al (2008) Live imaging of emerging hematopoietic stem cells and early thymus colonization. Blood 111:1147–1156

    CAS  Article  Google Scholar 

  14. 14.

    Kissa K, Herbomel P (2010) Blood stem cells emerge from aortic endothelium by a novel type of cell transition. Nature 464:112–115

    CAS  Article  Google Scholar 

  15. 15.

    Bertrand JY et al (2010) Haematopoietic stem cells derive directly from aortic endothelium during development. Nature 464:108–111

    CAS  Article  Google Scholar 

  16. 16.

    Robin C et al (2009) Human placenta is a potent hematopoietic niche containing hematopoietic stem and progenitor cells throughout development. Cell Stem Cell 5:385–395

    CAS  Article  Google Scholar 

  17. 17.

    Kimmel CB, Ballard WW, Kimmel SR, Ullmann B, Schilling TF (1995) Stages of embryonic development of the zebrafish. Dev Dyn 203:253–310

    CAS  Article  Google Scholar 

  18. 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 457:887–891

    CAS  Article  Google Scholar 

  19. 19.

    Lancino M et al (2018) Anisotropic organization of circumferential actomyosin characterizes hematopoietic stem cells emergence in the zebrafish. Elife 7:1–36

    Article  Google Scholar 

  20. 20.

    Fukuhara S et al (2014) Visualizing the cell-cycle progression of endothelial cells in zebrafish. Dev Biol 393:10–23

    CAS  Article  Google Scholar 

  21. 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 64:822–832

    CAS  Article  Google Scholar 

  22. 22.

    Helker CSM et al (2013) The zebrafish common cardinal veins develop by a novel mechanism: lumen ensheathment. Development 140:2776–2786

    CAS  Article  Google Scholar 

  23. 23.

    Lin H-F et al (2005) Analysis of thrombocyte development in CD41-GFP transgenic zebrafish. Blood 106:3803–3810

    CAS  Article  Google Scholar 

  24. 24.

    Golushko IY, Rochal SB, Lorman VL (2015) Complex instability of axially compressed tubular lipid membrane with controlled spontaneous curvature. Eur Phys J E 38:112

    Article  Google Scholar 

  25. 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 82:1995–1998

    Article  Google Scholar 

  26. 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 59:758–774

    Article  Google Scholar 

  27. 27.

    Muñoz MA (2018) Colloquium: criticality and dynamical scaling in living systems. Rev Mod Phys 90:031001

    Article  Google Scholar 

  28. 28.

    Santoro MM, Pesce G, Stainier DY (2009) Characterization of vascular mural cells during zebrafish development. Mech Dev 126:638–649

    CAS  Article  Google Scholar 

  29. 29.

    Campàs O (2016) A toolbox to explore the mechanics of living embryonic tissues. Semin Cell Dev Biol 55:119–130

    Article  Google Scholar 

  30. 30.

    Wyatt T, Baum B, Charras G (2016) A question of time: tissue adaptation to mechanical forces. Curr Opin Cell Biol 38:68–73

    CAS  Article  Google Scholar 

  31. 31.

    Landau LD, Lifshitz EM (1980) Statistical physics, part 1. In: Sykes JB, Kearsley MJ (eds) Theoretical physics, vol 5. Butterworth-Heinemann, Oxford

  32. 32.

    Timoshenko S, Goodier JN (1951) Theory of elasticity. McGraw-Hill Book Company Inc., New York

  33. 33.

    Guillot C, Lecuit T (2013) Mechanics of epithelial tissue homeostasis and morphogenesis. Science (80-.) 340:1185–1189

    CAS  Article  Google Scholar 

  34. 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 11:1847–1857

    CAS  Article  Google Scholar 

  35. 35.

    Bi D, Yang X, Marchetti MC, Manning ML (2016) Motility-driven glass and jamming transitions in biological tissues. Phys Rev X 6:021011

    PubMed  PubMed Central  Google Scholar 

  36. 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 17:2095–2104

    CAS  Article  Google Scholar 

  37. 37.

    Merkel M et al (2017) Triangles bridge the scales: quantifying cellular contributions to tissue deformation. Phys Rev E 95:032401

    Article  Google Scholar 

  38. 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

    Article  PubMed  Google Scholar 

  39. 39.

    Chi NC et al (2008) Foxn4 directly regulates tbx2b expression and atrioventricular canal formation. Genes Dev 22:734–739

    CAS  Article  Google Scholar 

  40. 40.

    Blum Y et al (2008) Complex cell rearrangements during intersegmental vessel sprouting and vessel fusion in the zebrafish embryo. Dev Biol 316:312–322

    CAS  Article  Google Scholar 

  41. 41.

    Westerfield M (2000) The zebrafish book. A guide for the laboratory use of zebrafish (Danio rerio), 4th edn. Univ. of Oregon Press, Eugene

  42. 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 6:1897–1904

    CAS  Article  Google Scholar 

Download references

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.

Author information

Affiliations

Authors

Corresponding author

Correspondence to Karima Kissa.

Ethics declarations

Conflict of interest

The authors declare no competing financial interests.

Additional information

We dedicate this work to the memory of our friend and colleague, V. Lorman.

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Electronic supplementary material

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

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

Download citation

Keywords

  • Haematopoiesis
  • Zebrafish
  • Endothelial-to-haematopoietic transition
  • 4D microscopy
  • Modeling