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单细胞测序揭示了脊髓损伤后特定内皮细胞亚群诱导小胶质细胞血管生成。

Single-cell sequencing reveals microglia induced angiogenesis by specific subsets of endothelial cells following spinal cord injury.

机构信息

Key Laboratory of Neuroregeneration of Jiangsu and Ministry of Education, NMPA Key Laboratory for Research and Evaluation of Tissue Engineering Technology Products, Co-innovation Center of Neuroregeneration, Nantong University, Nantong, China.

Jiangsu Clinical Medicine Center of Tissue Engineering and Nerve Injury Repair, Affiliated Hospital of Nantong University, Nantong University, Nantong, China.

出版信息

FASEB J. 2022 Jul;36(7):e22393. doi: 10.1096/fj.202200337R.

DOI:10.1096/fj.202200337R
PMID:35699080
Abstract

Spinal cord injury (SCI) results in dynamic alterations of the microenvironment at the lesion site, which inevitably leads to neuronal degeneration and functional impairment. The destruction of the spinal vascular system leads to a significant deterioration of the milieu, which exacerbates inflammatory response and deprives cells of nutrient support in the lesion. Limited endogenous angiogenesis occurs after SCI, but the cellular events at the lesion site during this process are unclear so far. Here, we performed single-cell RNA sequencing (scRNA-seq) on spinal cord tissues of rats at different time points after SCI. After clustering and cell-type identification, we focused on vascular endothelial cells (ECs), which play a pivotal role in angiogenesis, and drew the cellular and molecular atlas for angiogenesis after SCI. We found that microglia and macrophages promote endogenous angiogenesis by regulating EC subsets through SPP1 and IGF signaling pathways. Our results indicate that immune cells promote angiogenesis by regulating specific subsets of vascular ECs, which provides new clues for exploring SCI intervention.

摘要

脊髓损伤(SCI)导致损伤部位微环境发生动态改变,不可避免地导致神经元变性和功能障碍。脊髓血管系统的破坏导致环境显著恶化,加剧炎症反应并使损伤部位的细胞失去营养支持。SCI 后会发生有限的内源性血管生成,但目前尚不清楚在此过程中损伤部位的细胞事件。在这里,我们对 SCI 后不同时间点的大鼠脊髓组织进行了单细胞 RNA 测序(scRNA-seq)。在聚类和细胞类型鉴定后,我们专注于血管内皮细胞(ECs),它们在血管生成中起着关键作用,并绘制了 SCI 后血管生成的细胞和分子图谱。我们发现小胶质细胞和巨噬细胞通过 SPP1 和 IGF 信号通路调节 EC 亚群来促进内源性血管生成。我们的结果表明,免疫细胞通过调节血管内皮细胞的特定亚群来促进血管生成,这为探索 SCI 干预提供了新的线索。

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