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在发育性中枢神经系统髓鞘形成中对 ADGRG1/GPR56 功能的细胞类型特异性评估。

Cell type-specific evaluation of ADGRG1/GPR56 function in developmental central nervous system myelination.

机构信息

Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, University of California at San Francisco, San Francisco, California, USA.

Department of Medicine, Children's Hospital and Harvard Medical School, Boston, Massachusetts, USA.

出版信息

Glia. 2021 Feb;69(2):413-423. doi: 10.1002/glia.23906. Epub 2020 Sep 9.

Abstract

Myelination of axons in the central nervous system (CNS) is a concerted effort between many cell types, resulting in significant cross-talk and communication among cells. Adhesion G protein-coupled receptor ADGRG1 (GPR56) is expressed in all major glial cells and regulates a wide variety of physiological processes by mediating cell-cell and cell-matrix communications. Previous literature has demonstrated the requirement of ADGRG1 in oligodendrocyte precursor cells (OPCs) during developmental myelination. However, it is unknown if ADGRG1 is responsible for myelin formation in a cell-type-specific manner. To that end, here we profiled myelin status in response to deletion of Adgrg1 specifically in OPCs, microglia, astrocytes, and neurons. Interestingly, we find that knocking out Adgrg1 in OPCs significantly decreases OPC proliferation and reduced number of myelinated axons. However, deleting Adgrg1 in microglia, astrocytes, and neurons does not impact developmental myelination. These data support an autonomous functional role for Adgrg1 in OPCs related to myelination.

摘要

中枢神经系统(CNS)轴突的髓鞘形成是多种细胞共同作用的结果,导致细胞之间存在显著的串扰和通讯。黏附 G 蛋白偶联受体 ADGRG1(GPR56)在所有主要的神经胶质细胞中表达,并通过介导细胞-细胞和细胞-基质通讯来调节广泛的生理过程。先前的文献已经证明了 ADGRG1 在少突胶质前体细胞(OPC)发育性髓鞘形成过程中的必要性。然而,尚不清楚 ADGRG1 是否以细胞类型特异性的方式负责髓鞘形成。为此,我们专门在 OPCs、小胶质细胞、星形胶质细胞和神经元中对 Adgrg1 缺失进行了髓鞘状态分析。有趣的是,我们发现特异性敲除 OPC 中的 Adgrg1 会显著降低 OPC 的增殖并减少髓鞘化轴突的数量。然而,在小胶质细胞、星形胶质细胞和神经元中删除 Adgrg1 并不影响发育性髓鞘形成。这些数据支持 Adgrg1 在与髓鞘形成相关的 OPCs 中具有自主功能作用。

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