Microglial ASD-related genes are involved in oligodendrocyte differentiation.
Microglial ASD-related genes are involved in oligodendrocyte differentiation.
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DOI：
10.1038/s41598-021-97257-9
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发表时间：
2021-09-08
影响因子：
4.6
通讯作者：
Muramatsu R
中科院分区：
文献类型：
--
作者：
Takanezawa Y;Tanabe S;Kato D;Ozeki R;Komoda M;Suzuki T;Baba H;Muramatsu R
自闭症谱系障碍(ASD)与染色体结构域解旋酶DNA结合蛋白8(CHD8)和结节性硬化症复合体2(TSC2)的突变有关。虽然这些ASD相关基因在小胶质细胞等神经胶质细胞中被检测到，但CHD8或TSC2缺乏对小胶质细胞功能和小胶质细胞介导的脑发育的影响仍不清楚。在这项研究中，我们研究了小胶质细胞CHD8和TSC2在体外神经干细胞(NSCs)细胞因子表达、吞噬活性和神经/神经胶质形成中的作用。在脂多糖(LPS)刺激下，小胶质细胞中CHD8或TSC2基因敲除可降低胰岛素样生长因子-1(IGF1)的表达。此外，TSC2缺乏可抑制巨噬细胞吞噬功能，抑制小胶质细胞介导的少突胶质细胞发育，尤其是CHD8或TSC2缺乏可阻止少突胶质前体细胞向少突胶质细胞分化。这些结果提示ASD相关基因在小胶质细胞中的表达参与了少突胶质细胞的分化，这可能与ASD相关的白质病理有关。
Autism spectrum disorders (ASD) are associated with mutations of chromodomain-helicase DNA-binding protein 8 (Chd8) and tuberous sclerosis complex 2 (Tsc2). Although these ASD-related genes are detected in glial cells such as microglia, the effect of Chd8 or Tsc2 deficiency on microglial functions and microglia-mediated brain development remains unclear. In this study, we investigated the role of microglial Chd8 and Tsc2 in cytokine expression, phagocytosis activity, and neuro/gliogenesis from neural stem cells (NSCs) in vitro. Chd8 or Tsc2 knockdown in microglia reduced insulin-like growth factor-1(Igf1) expression under lipopolysaccharide (LPS) stimulation. In addition, phagocytosis activity was inhibited by Tsc2 deficiency, microglia-mediated oligodendrocyte development was inhibited, in particular, the differentiation of oligodendrocyte precursor cells to oligodendrocytes was prevented by Chd8 or Tsc2 deficiency. These results suggest that ASD-related gene expression in microglia is involved in oligodendrocyte differentiation, which may contribute to the white matter pathology relating to ASD.
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影响因子：
4.3
作者：
Barnard RA;Pomaville MB;O'Roak BJ
通讯作者：
O'Roak BJ
影响因子：
5.5
作者：
Domingues HS;Portugal CC;Socodato R;Relvas JB
通讯作者：
Relvas JB
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作者：
Arno, Benedetta;Grassivaro, Francesca;Muzio, Luca
通讯作者：
Muzio, Luca
影响因子：
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作者：
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通讯作者：
Spengler D
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16.6
作者：
Castelijns, Bas;Baak, Mirna L.;Creyghton, Menno P.
通讯作者：
Creyghton, Menno P.