Fibrotic scar tissue limits central nervous system regeneration in adult mammals. The extent of fibrotic tissue generation and distribution of stromal cells across different lesions in the brain and spinal cord has not been systematically investigated in mice and humans. Furthermore, it is unknown whether scar-forming stromal cells have the same origin throughout the central nervous system and in different types of lesions. In the current study, we compared fibrotic scarring in human pathological tissue and corresponding mouse models of penetrating and non-penetrating spinal cord injury, traumatic brain injury, ischemic stroke, multiple sclerosis and glioblastoma. We show that the extent and distribution of stromal cells are specific to the type of lesion and, in most cases, similar between mice and humans. Employing in vivo lineage tracing, we report that in all mouse models that develop fibrotic tissue, the primary source of scar-forming fibroblasts is a discrete subset of perivascular cells, termed type A pericytes. Perivascular cells with a type A pericyte marker profile also exist in the human brain and spinal cord. We uncover type A pericyte-derived fibrosis as a conserved mechanism that may be explored as a therapeutic target to improve recovery after central nervous system lesions.

纤维化疤痕组织限制了成年哺乳动物的中枢神经系统再生。纤维化组织生成的程度以及基质细胞在大脑和脊髓不同病变中的分布尚未在小鼠和人类中进行系统研究。此外，尚不清楚在整个中枢神经系统和不同类型的病变中形成疤痕的基质细胞是否具有相同的起源。在当前的研究中，我们比较了人类病理组织中的纤维化疤痕以及相应的穿透性和非穿透性脊髓损伤、创伤性脑损伤、缺血性中风、多发性硬化症和胶质母细胞瘤小鼠模型。我们发现，基质细胞的范围和分布因病变类型而异，并且在大多数情况下，小鼠和人类之间的情况相似。采用体内谱系追踪，我们报告在所有产生纤维化组织的小鼠模型中，形成疤痕的成纤维细胞的主要来源是血管周围细胞的离散子集，称为A型周细胞。具有 A 型周细胞标记谱的血管周围细胞也存在于人脑和脊髓中。我们发现 A 型周细胞衍生的纤维化是一种保守机制，可作为改善中枢神经系统损伤后恢复的治疗靶点。