PDF(Pubmed)
Abstract：
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 cholesterol 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.
摘要：
脊髓损伤（SCI）导致病变部位纤维化瘢痕形成，然而，纤维化瘢痕的异质性仍然难以捉摸。在这里，我们展示了分布的异质性，origin,和成纤维细胞在小鼠和雌性猴子SCI后纤维化疤痕内的功能。利用谱系追踪和单细胞RNA测序（scRNA-seq），我们发现血管周围成纤维细胞（PFs），和脑膜成纤维细胞（MFs），而不是周细胞/血管平滑肌细胞（vSMC），主要导致横切和挤压SCI中的纤维化瘢痕。来自脑膜的Crabp2+/Emb+成纤维细胞（CE-F）主要位于纤维化疤痕的中央区，显示I型胶原蛋白和纤连蛋白的胆固醇合成和分泌增强。相比之下,血管周围/血管周围Lama1+/Lama2+成纤维细胞（LA-F）主要见于病变的周围，表达层粘连蛋白和IV型胶原蛋白，并在功能上参与血管生成和脂质运输。这些发现可能为SCI后重塑异质性纤维化瘢痕提供了全面的理解。
