Mesquita Peixoto Márcia, Soares-da-Silva Francisca, Bonnet Valentin, Zhou Yanping, Ronteix Gustave, Santos Rita Faria, Mailhe Marie-Pierre, Nogueira Gonçalo, Feng Xing, Pereira João Pedro, Azzoni Emanuele, Anselmi Giorgio, de Bruijn Marella F T R, Perkins Archibald, Baroud Charles N, Pinto-do-Ó Perpétua, Cumano Ana
Immunology Department, Unit of Lymphocytes and Immunity, Institut Pasteur, Paris, France.
INSERM U1223 , Paris, France.
J Exp Med. 2025 Feb 3;222(2). doi: 10.1084/jem.20240592. Epub 2025 Jan 7.
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.
胚胎造血细胞在胎儿肝脏（FL）中发育，周围是各种非造血基质细胞。然而，在FL发育过程中基质的空间组织和细胞因子产生模式仍知之甚少。在这里，我们对早期（E12.5 - 14.5）FL阶段的造血和基质细胞群体进行了表征和绘图，发现虽然肝细胞是造血生长因子的主要来源，但其他基质细胞，包括间充质细胞、间皮细胞和内皮细胞，也参与了这个信号网络。使用专门的图像分析流程，我们量化了细胞与组织结构的距离并定义了邻域关系，发现不同的造血祖细胞对相邻基质细胞表现出不同的偏好，并在空间分布上显示出发育变化。值得注意的是，我们的数据表明间皮下区域在早期胎儿造血中起重要作用。这种方法为研究生物系统中复杂的细胞相互作用提供了有价值的工具，为发育过程中的造血微环境组织提供了新的见解。
