Single-cell transcriptome analysis reveals the immune heterogeneity and the repopulation of microglia by Hif1α in mice after spinal cord injury.
Single-cell transcriptome analysis reveals the immune heterogeneity and the repopulation of microglia by Hif1α in mice after spinal cord injury.
复制标题
单细胞转录组分析揭示了脊髓损伤后小鼠小胶质细胞的免疫异质性以及缺氧诱导因子1α（Hif1α）介导的小胶质细胞再增殖情况。
DOI：
10.1038/s41419-022-04864-z
复制
发表时间：
2022-05-03
影响因子：
9
通讯作者：
Zhu, Yongjian
中科院分区：
文献类型：
--
作者：
Wang, Jingyu;Xu, Lintao;Lin, Weiwei;Yao, Yin;Li, Heyangzi;Shen, Gerong;Cao, Xi;He, Ning;Chen, Jun;Hu, Jue;Zheng, Mingzhi;Song, Xinghui;Ding, Yuemin;Shen, Yueliang;Zhong, Jinjie;Wang, Lin-lin;Chen, Ying-ying;Zhu, Yongjian
神经炎症被认为是脊髓损伤（SCI）的一个重要病理过程，它可以清除受损组织，分泌细胞因子，促进再生。小胶质细胞的再生已被证明有利于脊髓损伤的恢复。然而，脊髓损伤后小胶质细胞再生的起源和调控因素尚不清楚。在这里，我们使用单细胞RNA测序来描绘小鼠脊髓损伤早期和晚期免疫细胞的动态转录景观。生理条件下位于脑膜内的B细胞和migdc参与免疫监视。小胶质细胞迅速减少，外周髓细胞在损伤后3天浸润。14 dpi时，小胶质细胞再生，髓细胞减少，淋巴细胞浸润。重要的是，体内对nestin+和Cx3cr1+细胞的遗传谱系追踪表明，小胶质细胞的再生来源于脊髓损伤后残留的小胶质细胞。我们发现在脊髓损伤后早期，残留的小胶质细胞回归到发育生长状态。Hif1α促进小胶质细胞增殖。条件消融小胶质细胞中的Hif1α可导致脊髓损伤后期病变面积增大，轴突纤维减少，功能恢复受损。我们的研究结果描绘了脊髓损伤的免疫异质性，并提出了靶向Hif1α可能有助于脊髓损伤后轴突再生和功能恢复的可能性。
Neuroinflammation is regarded as a vital pathological process in spinal cord injury (SCI), which removes damaged tissue, secretes cytokines, and facilitates regeneration. Repopulation of microglia has been shown to favor recovery from SCI. However, the origin and regulatory factors of microglia repopulation after SCI remain unknown. Here, we used single-cell RNA sequencing to portray the dynamic transcriptional landscape of immune cells during the early and late phases of SCI in mice. B cells and migDCs, located in the meninges under physiological conditions, are involved in immune surveillance. Microglia quickly reduced, and peripheral myeloid cells infiltrated three days-post-injury (dpi). At 14 dpi, microglia repopulated, myeloid cells were reduced, and lymphocytes infiltrated. Importantly, genetic lineage tracing of nestin+ and Cx3cr1+ cells in vivo showed that the repopulation of microglia was derived from residual microglia after SCI. We found that residual microglia regress to a developmental growth state in the early stages after SCI. Hif1α promotes microglial proliferation. Conditional ablation of Hif1α in microglia causes larger lesion sizes, fewer axon fibers, and impaired functional recovery in the late stages after SCI. Our results mapped the immune heterogeneity in SCI and raised the possibility that targeting Hif1α may help in axon regeneration and functional recovery after SCI.
登录
查看更多内容
影响因子：
82.9
作者：
Li Y;Lucas-Osma AM;Black S;Bandet MV;Stephens MJ;Vavrek R;Sanelli L;Fenrich KK;Di Narzo AF;Dracheva S;Winship IR;Fouad K;Bennett DJ
通讯作者：
Bennett DJ
影响因子：
15.9
作者：
Kreutzberg, GW
通讯作者：
Kreutzberg, GW
影响因子：
3.3
作者：
Guo, Xiaodong;Feng, Yaping;Huang, Hongyun
通讯作者：
Huang, Hongyun
影响因子：
32.4
作者：
Hammond, Timothy R.;Dufort, Connor;Stevens, Beth
通讯作者：
Stevens, Beth
影响因子：
32.4
作者：
Guilliams M;Dutertre CA;Scott CL;McGovern N;Sichien D;Chakarov S;Van Gassen S;Chen J;Poidinger M;De Prijck S;Tavernier SJ;Low I;Irac SE;Mattar CN;Sumatoh HR;Low GHL;Chung TJK;Chan DKH;Tan KK;Hon TLK;Fossum E;Bogen B;Choolani M;Chan JKY;Larbi A;Luche H;Henri S;Saeys Y;Newell EW;Lambrecht BN;Malissen B;Ginhoux F
通讯作者：
Ginhoux F