Spatiotemporal Dynamics of the Molecular Expression Pattern and Intercellular Interactions in the Glial Scar Response to Spinal Cord Injury.
Spatiotemporal Dynamics of the Molecular Expression Pattern and Intercellular Interactions in the Glial Scar Response to Spinal Cord Injury.
复制标题
脊髓损伤胶质疤痕反应中分子表达模式和细胞间相互作用的时空动态
DOI：
10.1007/s12264-022-00897-8
复制
发表时间：
2023-02
影响因子：
5.6
通讯作者：
Zhou, Songlin
中科院分区：
文献类型：
--
作者：
Gong, Leilei;Gu, Yun;Han, Xiaoxiao;Luan, Chengcheng;Liu, Chang;Wang, Xinghui;Sun, Yufeng;Zheng, Mengru;Fang, Mengya;Yang, Shuhai;Xu, Lai;Sun, Hualin;Yu, Bin;Gu, Xiaosong;Zhou, Songlin
关键词：
成年哺乳动物脊髓中的神经再生很差，因为缺乏神经元的内在再生和外在因素-胶质瘢痕由损伤触发并抑制或促进再生。空间转录组学（ST）的最新技术进展提供了一个独特的机会，破译大多数基因系统地在整个瘢痕形成，这仍然是知之甚少。在这里，我们首先使用32个脊髓损伤后的ST构建了小鼠脊髓在疤痕形成过程中的全组织基因表达模式。在局部，我们分析了从疤痕区域的前沿到核心的基因表达梯度，以进一步了解疤痕微环境，如神经递质紊乱、促炎反应的激活、神经毒性饱和脂质、血管生成、轴突延伸受阻和细胞外结构重组。此外，我们还描述了瘢痕形成过程中的21种细胞转录状态，并描绘了成纤维细胞、神经胶质细胞和免疫细胞亚群的起源、功能多样性和可能的轨迹。具体而言，我们发现了一些特殊细胞类型的调节因子，如巨噬细胞中的Thbs 1和Col 1a 2，成纤维细胞中的CD 36和Postn，小胶质细胞中的Plxnb 2和Nxpe 3，星形胶质细胞中的Clu和少突胶质细胞中的CD 74。此外，在手术后给予丹参素酸B（一种血脑屏障渗透和CD 36抑制剂），发现其可治疗纤维化。随后，我们描述了瘢痕边界的范围，并分析了相邻簇边界处的双向配体-受体相互作用，有助于在神经胶质增生和纤维化期间维持瘢痕结构，并发现GPR37L1_PSAP和GPR37_PSAP是小胶质细胞、成纤维细胞和星形胶质细胞中最重要的基因对。最后，我们量化了瘢痕驻留细胞的比例，并提出了瘢痕形成的四个可能阶段：巨噬细胞浸润，瘢痕驻留细胞的增殖和分化，瘢痕出现和瘢痕静止。总之，这些轮廓描绘了瘢痕的空间异质性，证实了以前关于瘢痕结构的概念，为瘢痕形成提供了一些新的线索，并为中枢神经系统损伤的治疗提供了宝贵的资源。在线版本包含补充材料，可通过10.1007/s12264-022-00897-8获取。
Nerve regeneration in adult mammalian spinal cord is poor because of the lack of intrinsic regeneration of neurons and extrinsic factors – the glial scar is triggered by injury and inhibits or promotes regeneration. Recent technological advances in spatial transcriptomics (ST) provide a unique opportunity to decipher most genes systematically throughout scar formation, which remains poorly understood. Here, we first constructed the tissue-wide gene expression patterns of mouse spinal cords over the course of scar formation using ST after spinal cord injury from 32 samples. Locally, we profiled gene expression gradients from the leading edge to the core of the scar areas to further understand the scar microenvironment, such as neurotransmitter disorders, activation of the pro-inflammatory response, neurotoxic saturated lipids, angiogenesis, obstructed axon extension, and extracellular structure re-organization. In addition, we described 21 cell transcriptional states during scar formation and delineated the origins, functional diversity, and possible trajectories of subpopulations of fibroblasts, glia, and immune cells. Specifically, we found some regulators in special cell types, such as Thbs1 and Col1a2 in macrophages, CD36 and Postn in fibroblasts, Plxnb2 and Nxpe3 in microglia, Clu in astrocytes, and CD74 in oligodendrocytes. Furthermore, salvianolic acid B, a blood–brain barrier permeation and CD36 inhibitor, was administered after surgery and found to remedy fibrosis. Subsequently, we described the extent of the scar boundary and profiled the bidirectional ligand-receptor interactions at the neighboring cluster boundary, contributing to maintain scar architecture during gliosis and fibrosis, and found that GPR37L1_PSAP, and GPR37_PSAP were the most significant gene-pairs among microglia, fibroblasts, and astrocytes. Last, we quantified the fraction of scar-resident cells and proposed four possible phases of scar formation: macrophage infiltration, proliferation and differentiation of scar-resident cells, scar emergence, and scar stationary. Together, these profiles delineated the spatial heterogeneity of the scar, confirmed the previous concepts about scar architecture, provided some new clues for scar formation, and served as a valuable resource for the treatment of central nervous system injury. The online version contains supplementary material available at 10.1007/s12264-022-00897-8.
登录
查看更多内容
影响因子：
6.1
作者：
Bazzigaluppi, Paolo;Weisspapir, Iliya;Carlen, Peter L.
通讯作者：
Carlen, Peter L.
脊髓损伤：病理生理学，多分子相互作用和潜在的恢复机制。
影响因子：
5.6
作者：
Anjum A;Yazid MD;Fauzi Daud M;Idris J;Ng AMH;Selvi Naicker A;Ismail OHR;Athi Kumar RK;Lokanathan Y
通讯作者：
Lokanathan Y
影响因子：
4.6
作者：
Bellei E;Vilella A;Monari E;Bergamini S;Tomasi A;Cuoghi A;Guerzoni S;Manca L;Zoli M;Pini LA
通讯作者：
Pini LA
影响因子：
16.2
作者：
Burda JE;Sofroniew MV
通讯作者：
Sofroniew MV
影响因子：
64.5
作者：
Asp, Michaela;Giacomello, Stefania;Lundeberg, Joakim
通讯作者：
Lundeberg, Joakim