Heterogeneous fibroblasts Contribute to fibrotic Scar Formation after Spinal Cord Injury in Mice and Monkeys
    作者: Xiaoyu Xue, Xianming Wu, Yongheng Fan, Shuyu Han, Haipeng Zhang, Yuting Sun, Yanyun Yin, Man Yin, Bing Chen, Zheng Sun, Shuaijing Zhao, Qi Zhang, Weiyuan Liu, Jiaojiao Zhang, Jiayin Li, Ya Shi, Zhifeng Xiao, Jianwu Dai, Yannan Zhao
    刊物名称: Nature Communications
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    摘要:
    Spinal cord injury (SCI) leads to fibrotic scar formation at the lesion site, yet the heterogeneity of fibrotic scar remains elusive. Here we show the heterogeneity in distribution, origin, and function of fibroblasts within fibrotic scars after SCI in mice and female monkeys. Utilizing lineage tracing and single-cell RNA sequencing (scRNA-seq), we found that perivascular fibroblasts (PFs), and meningeal fibroblasts (MFs), rather than pericytes/vascular smooth cells(vSMCs), primarily contribute to fibrotic scar in both transection and crush SCI. Crabp2 + /Emb+ fibroblasts (CE-F) derived from meninges primarily localize in the central region of fibrotic scars, demonstrating enhanced cho-lesterol synthesis and secretion of type I collagen and fibronectin. In contrast, perivascular/pial Lama1 + /Lama2+ fibroblasts (LA-F) are predominantly found at the periphery of the lesion, expressing laminin and type IV collagen and functionally involved in angiogenesis and lipid transport. These findings may provide a comprehensive understanding for remodeling heterogeneous fibrotic scars after SCI.