Macrophage depletion overcomes human hematopoietic cell engraftment failure in zebrafish embryo

Reine El Omar (1, 2) , Naoill Abdellaoui (3) , Safiatou T Coulibaly (4, 5) , Laura Fontenille (6) , François Lanza (2) , Christian Gachet (2) , Jean-Noël Freund (5, 7, 8) , Matteo Negroni (4, 5) , Karima Kissa (3, 6) , Manuela Tavian (7, 2, 5)

1 CITHEFOR - Cibles thérapeutiques, formulation et expertise pré-clinique du médicament
2 BPPS - Biologie et Pharmacologie des Plaquettes sanguines : hémostase, thrombose, transfusion
3 VBIC - Virulence Bactérienne et Infections Chroniques
4 ARN - Architecture et Réactivité de l'ARN
5 InnoVec - ITI Innovec
6 AZELEAD
7 IRFAC - Inserm U1113 - Interface de Recherche Fondamentale et Appliquée en Cancérologie
8 NGERE - Nutrition-Génétique et Exposition aux Risques Environnementaux

Abstract Zebrafish is widely adopted as a grafting model for studying human development and diseases. Current zebrafish xenotransplantations are performed using embryo recipients, as the adaptive immune system, responsible for host versus graft rejection, only reaches maturity at juvenile stage. However, transplanted primary human hematopoietic stem/progenitor cells (HSC) rapidly disappear even in zebrafish embryos, suggesting that another barrier to transplantation exists before the onset of adaptive immunity. Here, using a labelled macrophage zebrafish line, we demonstrated that engraftment of human HSC induces a massive recruitment of macrophages which rapidly phagocyte transplanted cells. Macrophages depletion, by chemical or pharmacological treatments, significantly improved the uptake and survival of transplanted cells, demonstrating the crucial implication of these innate immune cells for the successful engraftment of human cells in zebrafish. Beyond identifying the reasons for human hematopoietic cell engraftment failure, this work images the fate of human cells in real time over several days in macrophage-depleted zebrafish embryos.

Domaines: Biologie cellulaire

Reine El Omar, Naoill Abdellaoui, Safiatou T Coulibaly, Laura Fontenille, François Lanza, et al.. Macrophage depletion overcomes human hematopoietic cell engraftment failure in zebrafish embryo. Cell Death and Disease, 2024, 15 (5), pp.305. ⟨10.1038/s41419-024-06682-x⟩. ⟨hal-04567212⟩