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Spatiotemporal dynamics of cytokines expression dictate fetal liver hematopoiesis.

Peixoto, M. M.; Soares-da-Silva, F.; Bonnet, V.; Ronteix, G.; Santos, R. F.; Mailhe, M.-P.; Feng, X.; Pereira, J.; Azzoni, E.; Anselmi, G.; de Bruijn, M.; Baroud, C.; Pinto-do-O, P.; Cumano, A.

2023-08-25 developmental biology
10.1101/2023.08.24.554612 bioRxiv
Show abstract

During embryogenesis, yolk-sac and intra-embryonic-derived hematopoietic progenitors, comprising the precursors of adult hematopoietic stem cells, converge into the fetal liver. With a new staining strategy, we defined all non-hematopoietic components of the fetal liver and found that hepatoblasts are the major producers of hematopoietic growth factors. We identified mesothelial cells, a novel component of the stromal compartment, producing Kit ligand, a major hematopoietic cytokine. A high-definition imaging dataset analyzed using a deep-learning based pipeline allowed the unambiguous identification of hematopoietic and stromal populations, and enabled determining a neighboring network composition, at the single cell resolution. Throughout active hematopoiesis, progenitors preferentially associate with hepatoblasts, but not with stellate or endothelial cells. We found that, unlike yolk sac-derived progenitors, intra-embryonic progenitors respond to a chemokine gradient created by CXCL12-producing stellate cells. These results revealed that FL hematopoiesis is a spatiotemporal dynamic process, defined by an environment characterized by low cytokine concentrations.

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