Identification of Sox17 as a transcription factor that regulates oligodendrocyte development
Identification of Sox17 as a transcription factor that regulates oligodendrocyte development
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DOI：
10.1523/jneurosci.1716-06.2006
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发表时间：
2006-09-20
影响因子：
5.3
通讯作者：
Gallo, Vittorio
中科院分区：
文献类型：
--
作者：
Sohn, Jiho;Natale, JoAnne;Gallo, Vittorio
对通过荧光激活细胞分选术（FACS）从2 '，3'-环核苷酸3 '-磷酸二酯酶（CNP）增强的绿色荧光蛋白（EGFP）转基因小鼠中纯化的少突胶质细胞谱系细胞的微阵列分析显示，Sox 17（含有SRY盒的基因17）基因表达在出生后发育过程中与四个髓鞘基因的表达协同调节。在CNP-EGFP阳性（CNP-EGFP（+））细胞中，Sox 17 mRNA和蛋白水平在出生后第2天和第15天之间短暂增加，白色O 4（+）前少突胶质细胞表达的Sox 17水平高于Nkx 2.2（+）（NK 2转录因子相关，位点2）NG 2（+）或GalC（+）（半乳糖苷）细胞。在脊髓中，Sox 17蛋白表达在胚胎12.5 - 15.5天的初级运动神经元区域中检测不到，但在Nkx2.2（+）和CCl+细胞中明显。在培养的少突胶质祖细胞（OPCs）中，Sox 17水平在O 4（+）细胞中最高，并在从双极到多极的表型转换期间达到峰值。Sox 17和p27的平行增加发生在MBP蛋白表达之前，Sox 17上调被抑制分化的条件所阻止。Sox 17下调与小干扰RNA增加OPC增殖和减少有丝分裂原撤出后的谱系进展，而Sox 17过表达在有丝分裂原的存在下有相反的效果。Sox 17过表达增强OPCs中髓鞘基因的表达，并直接刺激MBP基因启动子的活性。这些发现支持Sox 17在控制少突胶质细胞祖细胞周期退出和分化中的重要作用。
Microarray analysis of oligodendrocyte lineage cells purified by fluorescence-activated cell sorting (FACS) from 2', 3'- cyclic nucleotide 3'-phosphodiesterase (CNP)-enhanced green fluorescent protein (EGFP) transgenic mice revealed Sox17 (SRY-box containing gene 17) gene expression to be coordinately regulated with that of four myelin genes during postnatal development. In CNP-EGFP-positive (CNP-EGFP(+)) cells, Sox17 mRNA and protein levels transiently increased between postnatal days 2 and 15, with white matter O4(+) preoligodendrocytes expressing greater Sox17 levels than Nkx2.2(+) ( NK2 transcription factor related, locus 2) NG2(+), or GalC(+) ( galactocerebroside) cells. In spinal cord, Sox17 protein expression was undetectable in the primary motor neuron domain between embryonic days 12.5 and 15.5 but was evident in Nkx2.2(+) and CCl+ cells. In cultured oligodendrocyte progenitor cells (OPCs), Sox17 levels were maximal in O4(+) cells and peaked during the phenotypic conversion from bipolar to multipolar. Parallel increases in Sox17 and p27 occurred before MBP protein expression, and Sox17 upregulation was prevented by conditions inhibiting differentiation. Sox17 down-regulation with small interfering RNAs increased OPC proliferation and decreased lineage progression after mitogen withdrawal, whereas Sox17 overexpression in the presence of mitogen had opposite effects. Sox17 overexpression enhanced myelin gene expression in OPCs and directly stimulated MBP gene promoter activity. These findings support important roles for Sox17 in controlling both oligodendrocyte progenitor cell cycle exit and differentiation.