Traumatic brain injury results in unique microglial and astrocyte transcriptomes enriched for type I interferon response.
Traumatic brain injury results in unique microglial and astrocyte transcriptomes enriched for type I interferon response.
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创伤性脑损伤导致独特的小胶质细胞和星形胶质细胞转录组富集 I 型干扰素反应。
DOI：
10.1186/s12974-021-02197-w
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发表时间：
2021-07-05
影响因子：
9.3
通讯作者：
Newell EA
中科院分区：
文献类型：
--
作者：
Todd BP;Chimenti MS;Luo Z;Ferguson PJ;Bassuk AG;Newell EA
创伤性脑损伤（TBI）是缺乏神经保护治疗的死亡和残疾的主要原因。TBI后，继发性损伤反应途径被激活，并导致持续的神经变性。小胶质细胞和星形胶质细胞是关键的神经免疫调节剂，在TBI后具有早期和持续的反应性。虽然组织学胶质细胞反应性已被很好地建立，但创伤后小胶质细胞和星形胶质细胞功能的精确理解仍然未知。成年雄性C57 BL/6 J小鼠接受液体冲击或假损伤。在损伤后7天对同时分离的小胶质细胞和星形胶质细胞进行RNA测序，以评估对TBI的细胞类型特异性转录反应。双重原位杂交和免疫荧光被用来验证TBI诱导的小胶质细胞和星形胶质细胞的基因表达变化，并确定表达这些基因的细胞的空间方向。在我们的胶质细胞转录组和先前报道的轻度TBI和其他神经系统疾病中进行比较分析，以确定重度TBI是否诱导小胶质细胞和星形胶质细胞活化的独特状态。我们的研究结果揭示了小胶质细胞和星形胶质细胞中持续的、谱系特异性的转录变化，在这个亚急性时间点，小胶质细胞表现出比星形胶质细胞更大的转录反应。小胶质细胞和星形胶质细胞显示出与I型干扰素信号传导和MHC I类抗原呈递相关的基因的重叠富集。小胶质细胞和星形胶质细胞对严重TBI的转录反应与先前在轻度TBI和其他神经退行性和神经炎症性疾病中的报道不同。同时谱系特异性分析揭示了新的TBI特异性转录变化;这些发现突出了TBI后神经胶质反应性的细胞类型特异性分析的重要性，并可能有助于识别新的靶向治疗。
Traumatic brain injury (TBI) is a leading cause of death and disability that lacks neuroprotective therapies. Following a TBI, secondary injury response pathways are activated and contribute to ongoing neurodegeneration. Microglia and astrocytes are critical neuroimmune modulators with early and persistent reactivity following a TBI. Although histologic glial reactivity is well established, a precise understanding of microglia and astrocyte function following trauma remains unknown. Adult male C57BL/6J mice underwent either fluid percussion or sham injury. RNA sequencing of concurrently isolated microglia and astrocytes was conducted 7 days post-injury to evaluate cell-type-specific transcriptional responses to TBI. Dual in situ hybridization and immunofluorescence were used to validate the TBI-induced gene expression changes in microglia and astrocytes and to identify spatial orientation of cells expressing these genes. Comparative analysis was performed between our glial transcriptomes and those from prior reports in mild TBI and other neurologic diseases to determine if severe TBI induces unique states of microglial and astrocyte activation. Our findings revealed sustained, lineage-specific transcriptional changes in both microglia and astrocytes, with microglia showing a greater transcriptional response than astrocytes at this subacute time point. Microglia and astrocytes showed overlapping enrichment for genes related to type I interferon signaling and MHC class I antigen presentation. The microglia and astrocyte transcriptional response to severe TBI was distinct from prior reports in mild TBI and other neurodegenerative and neuroinflammatory diseases. Concurrent lineage-specific analysis revealed novel TBI-specific transcriptional changes; these findings highlight the importance of cell-type-specific analysis of glial reactivity following TBI and may assist with the identification of novel, targeted therapies.
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影响因子：
7
作者：
Donato M;Xu Z;Tomoiaga A;Granneman JG;Mackenzie RG;Bao R;Than NG;Westfall PH;Romero R;Draghici S
通讯作者：
Draghici S
影响因子：
9.3
作者：
Early, Alexandria N.;Gorman, Amy A.;Morganti, Josh M.
通讯作者：
Morganti, Josh M.
影响因子：
8.8
作者：
Mathys H;Adaikkan C;Gao F;Young JZ;Manet E;Hemberg M;De Jager PL;Ransohoff RM;Regev A;Tsai LH
通讯作者：
Tsai LH
影响因子：
16.6
作者：
Arneson D;Zhang G;Ying Z;Zhuang Y;Byun HR;Ahn IS;Gomez-Pinilla F;Yang X
通讯作者：
Yang X
影响因子：
32.4
作者：
Hammond, Timothy R.;Dufort, Connor;Stevens, Beth
通讯作者：
Stevens, Beth