Distinct features of brain perivascular fibroblasts and mural cells revealed by in vivo two-photon imaging.

Distinct features of brain perivascular fibroblasts and mural cells revealed by in vivo two-photon imaging.
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DOI:
10.1177/0271678x211068528
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发表时间:
2022-06
影响因子:
6.3
通讯作者:
Shih, Andy Y.
Shih, Andy Y.
中科院分区:
医学1区
文献类型:
--
作者:
Bonney, Stephanie K.;Sullivan, Liam T.;Cherry, Timothy J.;Daneman, Richard;Shih, Andy Y.

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血管周围成纤维细胞(PVF)被认为在许多中枢神经系统疾病中具有促纤维化作用。与壁细胞一样,PVF包围血管并表达Pdgfrβ。然而,这些共有的属性阻碍了将PVF与壁细胞区分开的能力。我们使用体内双光子成像和转基因小鼠与PVF靶向启动子(Col 1a 1或Col 1a 2)比较PVF和壁细胞在健康成年小鼠大脑皮层的结构和分布。我们发现,PVFs定位于所有皮质穿透小动脉及其分支(小动脉-毛细血管过渡区),以及只有较大的升小静脉的主干。然而,毛细管区没有PVF覆盖。PVF显示沿血管壁沿着的短程移动性,并表现出平滑肌细胞或周细胞所未见的独特结构特征(扁平胞体和薄皱褶突起)。这些发现阐明了PVF和壁细胞是共存于相似的血管周围生态位中的不同细胞类型。
Perivascular fibroblasts (PVFs) are recognized for their pro-fibrotic role in many central nervous system disorders. Like mural cells, PVFs surround blood vessels and express Pdgfrβ. However, these shared attributes hinder the ability to distinguish PVFs from mural cells. We used in vivo two-photon imaging and transgenic mice with PVF-targeting promoters (Col1a1 or Col1a2) to compare the structure and distribution of PVFs and mural cells in cerebral cortex of healthy, adult mice. We show that PVFs localize to all cortical penetrating arterioles and their offshoots (arteriole-capillary transition zone), as well as the main trunk of only larger ascending venules. However, the capillary zone is devoid of PVF coverage. PVFs display short-range mobility along the vessel wall and exhibit distinct structural features (flattened somata and thin ruffled processes) not seen with smooth muscle cells or pericytes. These findings clarify that PVFs and mural cells are distinct cell types coexisting in a similar perivascular niche.