区域多样的星形胶质细胞亚型及其对 EAE 的异质反应,Glia

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区域多样的星形胶质细胞亚型及其对 EAE 的异质反应
Glia ( IF 5.4 ) Pub Date : 2020-12-17 , DOI: 10.1002/glia.23954
Malte Borggrewe ₁ , Corien Grit ₁ , Ilia D Vainchtein _{1,

2} , Nieske Brouwer ₁ , Evelyn M Wesseling ₁ , Jon D Laman ₁ , Bart J L Eggen ₁ , Susanne M Kooistra ₁ , Erik W G M Boddeke _{1,

3}

Affiliation

星形胶质细胞在中枢神经系统 (CNS) 中发挥许多功能，包括对血脑屏障、突触形成和营养支持的贡献。此外，它们可以引发炎症反应，并且在形态和功能上存在异质性。为了广泛表征星形胶质细胞亚型，我们通过 FACS 分离和基因表达分析了来自三个中枢神经系统区域的不同星形胶质细胞亚型；前脑、后脑和脊髓。根据 GLAST/SLC1A3 和 ACSA-2/ATP1B2 细胞表面表达分离星形胶质细胞亚群。局部大脑环境被证明是在星形胶质细胞亚型中建立不同转录程序的关键。在实验性自身免疫性脑脊髓炎 (EAE) 小鼠中，亚型之间的转录差异也很明显，这些星形胶质细胞亚型表现出不同的反应。虽然与血脑屏障维持相关的基因表达特征丢失，但脊髓星形胶质细胞中涉及神经炎症和神经毒性的特征增加，尤其是在急性疾病阶段。在 EAE 的慢性阶段，这种反应性星形胶质细胞特征略有下降，同时获得了更多的增殖特征，这可能与胶质瘢痕形成和组织再生有关。星形胶质细胞的形态异质性先前表明存在星形胶质细胞亚型，在这里我们展示了基于与大脑区域相关的转录组变异和对神经炎症损伤 (EAE) 的不同反应性的多样性。脊髓星形胶质细胞中涉及神经炎症和神经毒性的特征增加，尤其是在急性疾病阶段。在 EAE 的慢性阶段，这种反应性星形胶质细胞特征略有下降，同时获得了更多的增殖特征，这可能与胶质瘢痕形成和组织再生有关。星形胶质细胞的形态异质性先前表明存在星形胶质细胞亚型，在这里我们展示了基于与大脑区域相关的转录组变异和对神经炎症损伤 (EAE) 的不同反应性的多样性。脊髓星形胶质细胞中涉及神经炎症和神经毒性的特征增加，尤其是在急性疾病阶段。在 EAE 的慢性阶段，这种反应性星形胶质细胞特征略有下降，同时获得了更多的增殖特征，这可能与胶质瘢痕形成和组织再生有关。星形胶质细胞的形态异质性先前表明存在星形胶质细胞亚型，在这里我们展示了基于与大脑区域相关的转录组变异和对神经炎症损伤 (EAE) 的不同反应性的多样性。这可能与胶质瘢痕形成和组织再生有关。星形胶质细胞的形态异质性先前表明存在星形胶质细胞亚型，在这里我们展示了基于与大脑区域相关的转录组变异和对神经炎症损伤 (EAE) 的不同反应性的多样性。这可能与胶质瘢痕形成和组织再生有关。星形胶质细胞的形态异质性先前表明存在星形胶质细胞亚型，在这里我们展示了基于与大脑区域相关的转录组变异和对神经炎症损伤 (EAE) 的不同反应性的多样性。

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Regionally diverse astrocyte subtypes and their heterogeneous response to EAE

Astrocytes fulfil many functions in the central nervous system (CNS), including contribution to the blood brain barrier, synapse formation, and trophic support. In addition, they can mount an inflammatory response and are heterogeneous in morphology and function. To extensively characterize astrocyte subtypes, we FACS‐isolated and gene expression profiled distinct astrocyte subtypes from three central nervous system regions; forebrain, hindbrain and spinal cord. Astrocyte subpopulations were separated based on GLAST/SLC1A3 and ACSA‐2/ATP1B2 cell surface expression. The local brain environment proved key in establishing different transcriptional programs in astrocyte subtypes. Transcriptional differences between subtypes were also apparent in experimental autoimmune encephalomyelitis (EAE) mice, where these astrocyte subtypes showed distinct responses. While gene expression signatures associated with blood–brain barrier maintenance were lost, signatures involved in neuroinflammation and neurotoxicity were increased in spinal cord astrocytes, especially during acute disease stages. In chronic stages of EAE, this reactive astrocyte signature was slightly decreased, while obtaining a more proliferative profile, which might be relevant for glia scar formation and tissue regeneration. Morphological heterogeneity of astrocytes previously indicated the presence of astrocyte subtypes, and here we show diversity based on transcriptome variation associated with brain regions and differential responsiveness to a neuroinflammatory insult (EAE).

更新日期：2020-12-17

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