Department of Biochemistry and Molecular Biology, Cumming School of Medicine, Alberta Children's Hospital Research Institute, University of Calgary, 3330 Hospital Drive, Calgary, Alberta, T2N 4N1, Canada.
Department of Biochemistry and Molecular Biology, Cumming School of Medicine, Alberta Children's Hospital Research Institute, University of Calgary, 3330 Hospital Drive, Calgary, Alberta, T2N 4N1, Canada.
Dev Biol. 2023 Jun;498:35-48. doi: 10.1016/j.ydbio.2023.03.004. Epub 2023 Mar 16.
Fibroblasts play an important role in maintaining tissue integrity by secreting components of the extracellular matrix and initiating response to injury. Although the function of fibroblasts has been extensively studied in adults, the embryonic origin and diversification of different fibroblast subtypes during development remain largely unexplored. Using zebrafish as a model, we show that the sclerotome, a sub-compartment of the somite, is the embryonic source of multiple fibroblast subtypes including tenocytes (tendon fibroblasts), blood vessel associated fibroblasts, fin mesenchymal cells, and interstitial fibroblasts. High-resolution imaging shows that different fibroblast subtypes occupy unique anatomical locations with distinct morphologies. Long-term Cre-mediated lineage tracing reveals that the sclerotome also contributes to cells closely associated with the axial skeleton. Ablation of sclerotome progenitors results in extensive skeletal defects. Using photoconversion-based cell lineage analysis, we find that sclerotome progenitors at different dorsal-ventral and anterior-posterior positions display distinct differentiation potentials. Single-cell clonal analysis combined with in vivo imaging suggests that the sclerotome mostly contains unipotent and bipotent progenitors prior to cell migration, and the fate of their daughter cells is biased by their migration paths and relative positions. Together, our work demonstrates that the sclerotome is the embryonic source of trunk fibroblasts as well as the axial skeleton, and local signals likely contribute to the diversification of distinct fibroblast subtypes.
成纤维细胞通过分泌细胞外基质成分并启动对损伤的反应，在维持组织完整性方面发挥着重要作用。尽管成纤维细胞的功能在成人中得到了广泛研究，但在发育过程中不同成纤维细胞亚型的胚胎起源和多样化仍在很大程度上未被探索。我们使用斑马鱼作为模型，表明体节的一个亚区——体节软骨，是包括肌腱成纤维细胞、血管相关成纤维细胞、鳍间充质细胞和间质成纤维细胞在内的多种成纤维细胞亚型的胚胎来源。高分辨率成像显示，不同的成纤维细胞亚型占据独特的解剖位置，具有不同的形态。长期的 Cre 介导的谱系追踪揭示了体节软骨也有助于与轴向骨骼密切相关的细胞。体节软骨祖细胞的消融导致广泛的骨骼缺陷。利用光转化细胞谱系分析，我们发现不同背腹和前后位置的体节软骨祖细胞具有不同的分化潜力。单细胞克隆分析结合体内成像表明，在细胞迁移之前，体节软骨祖细胞大多包含单能和双能祖细胞，其后代细胞的命运受其迁移路径和相对位置的影响。总之，我们的工作表明体节软骨是躯干成纤维细胞和轴向骨骼的胚胎来源，局部信号可能有助于不同成纤维细胞亚型的多样化。
