Down-regulation of the POU transcription factor SCIP is an early event in oligodendrocyte differentiation in vitro.
Down-regulation of the POU transcription factor SCIP is an early event in oligodendrocyte differentiation in vitro.
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发表时间：
1992-09
期刊：
影响因子：
4.6
通讯作者：
E. Collarini;R. Kuhn;Caroline J. Marshall;E. Monuki;Greg Lemke;William D. Richardson
中科院分区：
文献类型：
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作者：
E. Collarini;R. Kuhn;Caroline J. Marshall;E. Monuki;Greg Lemke;William D. Richardson
POU 结构域转录因子 SCIP（也称为 Tst-1）与施万细胞（周围神经系统 (PNS) 的髓鞘形成细胞）的发育有关。我们研究了 SCIP 也可能在少突胶质细胞（中枢神经系统 (CNS) 的髓鞘形成细胞）的发育中发挥作用的可能性。我们通过免疫选择纯化少突胶质细胞前体（O-2A 祖细胞），并在血小板源性生长因子（PDGF）和碱性成纤维细胞生长因子（bFGF）存在的情况下培养它们，它们共同保持 O-2A 祖细胞增殖并防止少突胶质细胞分化。在这些培养条件下，O-2A 祖细胞表达高水平的 SCIP mRNA 和蛋白质，并且不表达髓磷脂特异性基因。当通过去除生长因子而启动少突胶质细胞分化时，SCIP mRNA 迅速下调，随后 SCIP 蛋白下降，髓磷脂特异性基因相继激活。 SCIP mRNA 的快速下调需要持续的蛋白质合成。在仅存在 PDGF 的情况下培养的 O-2A 祖细胞中，SCIP 表达下降至中等水平，并诱导低水平的髓磷脂基因产物。因此，O-2A祖细胞中SCIP的表达水平与髓磷脂基因表达水平呈负相关，表明SCIP可能参与少突胶质细胞谱系从增殖到分化的发育转变。当 O-2A 祖细胞在 10% 胎牛血清存在下培养时，它们会分化为 2 型星形胶质细胞而不是少突胶质细胞。 SCIP mRNA 在不表达髓磷脂基因的 2 型星形胶质细胞中也被下调，因此 SCIP 的下调似乎与细胞增殖本身的停止比与特定分化表型的表达更密切相关。
The POU-domain transcription factor SCIP (also known as Tst-1) has been implicated in the development of Schwann cells, the myelinating cells of the peripheral nervous system (PNS). We have investigated the possibility that SCIP also might play a role in the development of oligodendrocytes, the myelinating cells of the central nervous system (CNS). We purified oligodendrocyte precursors (O-2A progenitors) by immunoselection and cultured them in the presence of platelet-derived growth factor (PDGF) and basic fibroblast growth factor (bFGF), which together keep O-2A progenitors proliferating and prevent oligodendrocyte differentiation. Under these culture conditions, O-2A progenitors expressed high levels of SCIP mRNA and protein, and did not express myelin-specific genes. When oligodendrocyte differentiation was initiated by withdrawing the growth factors, SCIP mRNA was rapidly down-regulated, followed by a decline in SCIP protein and the sequential activation of myelin-specific genes. Rapid down-regulation of SCIP mRNA required continued protein synthesis. In O-2A progenitors that were cultured in the presence of PDGF alone, SCIP expression declined to an intermediate level, and low levels of the myelin gene products were induced. Thus, the level of SCIP expression in O-2A progenitors is inversely related to the level of myelin gene expression, suggesting that SCIP may be involved in the developmental switch from proliferation to differentiation in the oligodendrocyte lineage. When O-2A progenitors are cultured in the presence of 10% fetal calf serum, they differentiate into type-2 astrocytes rather than oligodendrocytes. SCIP mRNA was also down-regulated in type-2 astrocytes, which do not express myelin genes, so down-regulation of SCIP seems to be more closely linked to the cessation of cell proliferation per se than the expression of a particular differentiated phenotype.