Tang Xinyu Thomas, Chen Lin Veronica, Zhou Bo O
Key Laboratory of Multi-Cell Systems, Shanghai Institute of Biochemistry and Cell Biology, Center for Excellence in Molecular Cell Science, Chinese Academy of Sciences, University of Chinese Academy of Sciences, Shanghai, 200031, China.
State Key Laboratory of Experimental Hematology, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences, Tianjin, 300020, China.
Cell Regen. 2025 Apr 22;14(1):15. doi: 10.1186/s13619-025-00234-0.
The fetal liver is the primary site for the expansion of hematopoietic stem and progenitor cells (HSPCs) during fetal hematopoiesis. However, the spatial organization of different hematopoietic progenitor populations within the fetal liver remains poorly characterized. In this study, we utilized SeekSpace, a high-resolution single-nucleus spatial transcriptomics platform, to map the spatial distribution of hematopoietic stem cells and multipotent progenitor cells (HSC/MPPs) and downstream restricted progenitors (RPs) in relation to other hematopoietic and stromal cell populations in the fetal liver at embryonic day 13.5. Using SeekSpace, we constructed a detailed single-cell spatial transcriptomic atlas of fetal liver hematopoiesis, revealing that both HSC/MPPs and many RPs undergo active expansion in the fetal liver, a process distinct from their behavior in adult bone marrow. Proximity analysis and in situ imaging demonstrated that HSC/MPPs expansion occurs in close association with macrophages and endothelial cells throughout the fetal liver, supported by signaling pathways involving IGF and collagen. In contrast, RPs exhibited no specific spatial proximity to other cell populations during their expansion. Collectively, this study provides a comprehensive resource for understanding the spatial and molecular mechanisms underlying HSC/MPPs and RP expansion during fetal liver hematopoiesis.
胎儿肝脏是胎儿造血过程中造血干细胞和祖细胞（HSPCs）扩增的主要部位。然而，胎儿肝脏内不同造血祖细胞群体的空间组织特征仍不明确。在本研究中，我们利用高分辨率单核空间转录组学平台SeekSpace，绘制了胚胎第13.5天胎儿肝脏中造血干细胞和多能祖细胞（HSC/MPPs）以及下游定向祖细胞（RPs）相对于其他造血和基质细胞群体的空间分布。利用SeekSpace，我们构建了详细的胎儿肝脏造血单细胞空间转录组图谱，揭示了HSC/MPPs和许多RPs在胎儿肝脏中都经历活跃扩增，这一过程与其在成人骨髓中的行为不同。邻近分析和原位成像表明，HSC/MPPs的扩增在整个胎儿肝脏中与巨噬细胞和内皮细胞密切相关，这一过程受到涉及胰岛素样生长因子（IGF）和胶原蛋白的信号通路的支持。相比之下，RPs在扩增过程中与其他细胞群体没有特定的空间邻近关系。总的来说，这项研究为理解胎儿肝脏造血过程中HSC/MPPs和RPs扩增的空间和分子机制提供了全面的资源。
