Early embryonic NG2 glia are exclusively gliogenic and do not generate neurons in the brain
Early embryonic NG2 glia are exclusively gliogenic and do not generate neurons in the brain
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DOI：
10.1002/glia.23590
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发表时间：
2019-06-01
期刊：
影响因子：
6.2
通讯作者：
Kirchhoff, Frank
中科院分区：
文献类型：
--
作者：
Huang, Wenhui;Guo, Qilin;Kirchhoff, Frank
在中枢神经系统中，I型跨膜糖蛋白NG 2（神经胶质细胞抗原2）仅由周细胞和少突胶质细胞前体细胞（OPCs）表达。因此，OPC也被称为NG 2胶质细胞。它们在发育过程中的命运已在几种转基因小鼠模型中进行了系统研究。存在的共识是，出生后的NG 2胶质细胞仅限于少突胶质细胞（OL）谱系，而至少在前脑，胚胎NG 2胶质细胞也可以产生星形胶质细胞。此外，NG 2神经胶质细胞在早期胚胎脑（E16.5之前）的神经发生潜力的实验证据已经提供。然而，这一观察结果仍然存在争议。在这里，我们利用NG 2-EYFP和NG 2-CreERT 2敲入小鼠中可靠的转基因表达来研究早期胚胎NG 2胶质细胞的命运。虽然周细胞是在E12.5具有强NG 2基因活性的主要细胞，但在胚胎发生的早期阶段，只有少数OPC表达NG 2。随后，OPC的比例从3%（E12.5）分别增加到E14.5和E17.5的11%和25%。当Cre DNA重组酶活性在E12.5和E14.5诱导，并在出生后第0天（P0）和P10的幼崽进行了分析，绝大多数的重组细胞，除了周细胞，属于OL谱系细胞，与腹侧前脑中的星形胶质细胞很少。在其他脑区如脑干、小脑和嗅球中，仅检测到OL谱系细胞。因此，我们得出的结论是，来自早期胚胎脑的NG 2胶质细胞仅限于胶质细胞生成命运，并且在出生后不会分化为神经元。
In the central nervous system, the type I transmembrane glycoprotein NG2 (nerve-glia antigen 2) is only expressed by pericytes and oligodendrocyte precursor cells (OPCs). Therefore, OPCs are also termed NG2 glia. Their fate during development has been investigated systematically in several genetically modified mouse models. Consensus exists that postnatal NG2 glia are restricted to the oligodendrocyte (OL) lineage, while, at least in the forebrain, embryonic NG2 glia could also generate astrocytes. In addition, experimental evidence for a neurogenic potential of NG2 glia in the early embryonic brain (before E16.5) has been provided. However, this observation is still controversial. Here, we took advantage of reliable transgene expression in NG2-EYFP and NG2-CreERT2 knock-in mice to study the fate of early embryonic NG2 glia. While pericytes were the main cells with robust NG2 gene activity at E12.5, only a few OPCs expressed NG2 at this early stage of embryogenesis. Subsequently, this proportion of OPCs increased from 3% (E12.5) to 11% and 25% at E14.5 and E17.5, respectively. When Cre DNA recombinase activity was induced at E12.5 and E14.5 and pups were analyzed at postnatal day 0 (P0) and P10, the vast majority of recombined cells, besides pericytes, belonged to the OL lineage cells, with few astrocytes in the ventral forebrain. In other brain regions such as brain stem, cerebellum, and olfactory bulb only OL lineage cells were detected. Therefore, we conclude that NG2 glia from early embryonic brain are restricted to a gliogenic fate and do not differentiate into neurons after birth.