Spatiotemporal dynamics of fetal liver hematopoietic niches

胎儿肝脏造血生态位的时空动态

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作者:Márcia Mesquita Peixoto #, Francisca Soares-da-Silva #, Valentin Bonnet #, Yanping Zhou #, Gustave Ronteix, Rita Faria Santos, Marie-Pierre Mailhe, Gonçalo Nogueira, Xing Feng, João Pedro Pereira, Emanuele Azzoni, Giorgio Anselmi, Marella F T R de Bruijn, Archibald Perkins, Charles N Baroud #, Perpé

Abstract

Embryonic hematopoietic cells develop in the fetal liver (FL), surrounded by diverse non-hematopoietic stromal cells. However, the spatial organization and cytokine production patterns of the stroma during FL development remain poorly understood. Here, we characterized and mapped the hematopoietic and stromal cell populations at early (E12.5-14.5) FL stages, revealing that while hepatoblasts were the primary source of hematopoietic growth factors, other stromal cells-including mesenchymal, mesothelial, and endothelial cells-also contributed to this signaling network. Using a dedicated image analysis pipeline, we quantified cell distances to tissue structures and defined neighbor relationships, uncovering that different hematopoietic progenitors exhibit distinct preferences for neighboring stromal cells and show developmental changes in spatial distribution. Notably, our data suggest that the sub-mesothelium region plays a prominent role in early fetal hematopoiesis. This approach offers a valuable tool for studying complex cellular interactions in biological systems, providing new insights into hematopoietic niche organization during development.

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