Brain pericytes and perivascular fibroblasts are stromal progenitors with dual functions in cerebrovascular regeneration after stroke

Functional revascularization is key to stroke recovery and requires remodelling of blood vessels, around which is located the brain’s only stromal compartment. Stromal progenitor cells (SPC) form a functional grouping of cells critical for tissue regeneration following injury in many organs, yet their identity in the brain remains elusive despite implications in neovascularization and scar formation. Here we show that the perivascular niche of brain SPCs includes pericytes, venular smooth muscle cells and a distinct population of perivascular fibroblasts, that together help regenerate the cerebral microvasculature following stroke. The ischemic injury triggers amplification of pericytes and perivascular fibroblasts in the infarct region where they associate with endothelial cells inside a reactive astrocyte border. Fate-tracking of Hic1+ SPCs uncovers a transient functional and transcriptional phenotype of stroke-activated pericytes and perivascular fibroblasts, where both populations remain segregated, displaying dichotomous angiogenic and fibrogenic profiles. In the adult brain, pericytes and perivascular fibroblasts are therefore distinct subpopulations of stromal progenitors that coordinate revascularization and scar formation after injury. BioProject accession: PRJNA608615; SRA Study accession (temporary): SUB6996815

功能性血管重建（functional revascularization）是脑卒中康复的核心环节，其依赖于血管重塑，而血管周边正是大脑唯一的基质腔室（stromal compartment）。基质祖细胞（stromal progenitor cells, SPC）是一类功能协同的细胞群体，对多种器官损伤后的组织再生至关重要；尽管其在血管新生与瘢痕形成中具有潜在作用，但目前学界对其在大脑中的身份仍不明确。本研究证实，大脑SPC的血管周围微环境包含周细胞（pericytes）、静脉平滑肌细胞（venular smooth muscle cells）以及一类独特的血管周成纤维细胞（perivascular fibroblasts）群体，三者协同参与脑卒中后脑微血管的再生过程。缺血性损伤会触发梗死区域内周细胞与血管周成纤维细胞的增殖扩增，二者会在反应性星形胶质细胞（reactive astrocyte）边界处与内皮细胞（endothelial cells）发生结合。对Hic1阳性SPC的细胞命运追踪实验显示，脑卒中激活的周细胞与血管周成纤维细胞存在一过性的功能与转录表型，且两类细胞群体始终相互分离，分别呈现出截然不同的血管生成与纤维化特征。由此可见，在成年大脑中，周细胞与血管周成纤维细胞属于基质祖细胞的不同亚群，二者协同调控损伤后的血管重建与瘢痕形成过程。BioProject登录号：PRJNA608615；SRA研究临时登录号：SUB6996815