Sall1 is a transcriptional regulator defining microglia identity and function
Sall1 is a transcriptional regulator defining microglia identity and function
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DOI：
10.1038/ni.3585
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发表时间：
2016-12-01
影响因子：
30.5
通讯作者：
Greter, Melanie
中科院分区：
文献类型：
--
作者：
Buttgereit, Anne;Lelios, Iva;Greter, Melanie
小胶质细胞是中枢神经系统（CNS）的常驻巨噬细胞。基因表达谱已经确定了Sall 1，它编码一个转录调节因子，作为一个小胶质细胞的签名基因。我们发现，Sall 1表达的小胶质细胞，但不是由其他成员的单核吞噬细胞系统或其他CNS居民细胞。使用Sall 1进行小胶质细胞特异性基因靶向，我们发现细胞因子受体CSF 1 R参与了成人小胶质细胞的维持，并且细胞因子TGF-β的受体抑制了小胶质细胞的激活。然后，我们使用Sall 1的小胶质细胞特异性表达来诱导小鼠Sall 1基因座在体内，这导致小胶质细胞从静息组织巨噬细胞转化为炎性吞噬细胞，从而改变神经发生和扰乱组织稳态。总的来说，我们的研究结果表明，转录调控Sall 1保持小胶质细胞的身份和生理特性的中枢神经系统，并允许小胶质细胞特异性的操作在体内。
Microglia are the resident macrophages of the central nervous system (CNS). Gene expression profiling has identified Sall1, which encodes a transcriptional regulator, as a microglial signature gene. We found that Sall1 was expressed by microglia but not by other members of the mononuclear phagocyte system or by other CNS-resident cells. Using Sall1 for microglia-specific gene targeting, we found that the cytokine receptor CSF1R was involved in the maintenance of adult microglia and that the receptor for the cytokine TGF-beta suppressed activation of microglia. We then used the microglia-specific expression of Sall1 to inducibly inactivate the murine Sall1 locus in vivo, which resulted in the conversion of microglia from resting tissue macrophages into inflammatory phagocytes, leading to altered neurogenesis and disturbed tissue homeostasis. Collectively, our results show that transcriptional regulation by Sall1 maintains microglial identity and physiological properties in the CNS and allows microglia-specific manipulation in vivo.