Spatiotemporal dynamics of cytokines expression dictate fetal liver hematopoiesis.

Autor: Peixoto MM, Soares-da-Silva F, Bonnet V, Ronteix G, Santos RF, Mailhe MP, Feng X, Pereira JP, Azzoni E, Anselmi G, de Bruijn M, Baroud CN, Pinto-do-Ó P, Cumano A
Jazyk: angličtina
Zdroj: BioRxiv : the preprint server for biology [bioRxiv] 2023 Aug 25. Date of Electronic Publication: 2023 Aug 25.
DOI: 10.1101/2023.08.24.554612
Abstrakt: 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.
Databáze: MEDLINE