Spatiotemporal dynamics of cytokines expression dictate fetal liver hematopoiesis

Author:

Peixoto Marcia Mesquita,Soares-da-Silva Francisca,Bonnet Valentin,Ronteix Gustave,Santos Rita Faria,Mailhe Marie-Pierre,Feng Xing,Pereira João PedroORCID,Azzoni Emanuele,Anselmi Giorgio,de Bruijn Marella,Baroud Charles N.,Pinto-do-Ó Perpétua,Cumano Ana

Abstract

AbstractDuring 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.

Publisher

Cold Spring Harbor Laboratory

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