The morphodynamics of hematopoietic stem cell emergence: any incidence on cell fate ?
Hematopoietic Stem Cells (HSCs) at the origin of blood and immune cells are born during a narrow time window of the vertebrate embryonic development. HSCs precursor cells originate from blood vessels and in particular the ventral floor of the dorsal aorta. They do so according to a process referred to as the Endothelial-to Hematopoietic Transition (EHT) in which a subset of aortic cells, committed to enter a specific genetic program - in part controlled by the mechanical forces resulting from the blood flow -,extrude from the vascular wall. This extrusion process is relatively unique, partly owed to the biophysical conditions imposed by hemodynamic forces and also to the organization of the thin endothelial layer.
We have recently characterized the EHT process using the zebrafish embryo that offers unique advantages among which the relative easiness to perform live-imaging at high spatiotemporal resolution. We have shown that the EHT involves unusual cellular morphodynamics, with inward bending of both apical/luminal and basal membranes toward the sub-aortic space, anisotropic contraction of the cell apex contacting adjoining endothelial cells (supported by contractile circumferential actomyosin) and anisotropic organization of junctional complexes reinforced at antero-posterior poles (organized according to an axis that aligns with blood flow). Even more recently (unpublished work), we found that HSC precursor scan extrude via another type of emergence that does not involve cellular bending and that appears to require specific intercellular adhesion remodeling.
In this seminar, I will describe the specificities of the two types of EHT, including a model of differential adhesion remodeling (2D- versus 3D-displacement modes) and discuss the possibility of an impact of the mechanistic principles of EHT cell emergence on downstream cell fate.
CNRS UMR3738 Bases Génétiques, Moléculaires et Cellulaires du Développement - Institut Pasteur, Paris
Séminaire proposé par Giulia CARZEDDA