Duval D, Reinhardt B, Kedinger C, Boeuf H
Institut de Génétique et de Biologie Moléculaire et Cellulaire (CNRS/INSERM/ULP), BP 163, F-67404 ILLKIRCH Cedex, France.
FASEB J. 2000 Aug;14(11):1577-84. doi: 10.1096/fj.14.11.1577.
Mouse embryonic stem (ES) cells remain pluripotent in vitro when grown in the presence of leukemia inhibitory factor (LIF). LIF withdrawal results in progressive ES cell differentiation. Here we show that during this differentiation process, part of the cells undergo apoptosis concomitant with an activation of the p38 MAP kinase. To gain insight into events mediated by LIF in ES cells, the expression of potential candidate genes was analyzed in the absence or presence of this cytokine by using a semiquantitative RT-PCR assay. We focused on early response genes and on a new type of cytokine repressors (the Socs proteins), some of which exhibit anti-apoptotic properties. We found that expression of c-Fos, c-Jun, and JunB was induced upon LIF treatment whereas that of JunD, the tyrosine phosphatase ESP, and the components of the LIF receptor remained unaffected. Expression of Socs-3, but not Socs-1 or Socs-2, was stimulated in the presence of LIF. Finally, uncontrolled overexpression of Socs-1 and Socs-3 led to repression of LIF-dependent transcription and severely reduced cell viability, suggesting that the disturbance of a well balanced Socs protein content has adverse effects on cell survival.
小鼠胚胎干细胞（ES细胞）在白血病抑制因子（LIF）存在的情况下于体外培养时仍保持多能性。去除LIF会导致ES细胞逐渐分化。在此我们表明，在这个分化过程中，部分细胞发生凋亡，同时伴有p38丝裂原活化蛋白激酶的激活。为了深入了解LIF在ES细胞中介导的事件，通过使用半定量逆转录-聚合酶链反应（RT-PCR）分析，在有无这种细胞因子的情况下分析了潜在候选基因的表达。我们聚焦于早期反应基因以及一种新型的细胞因子抑制因子（即细胞因子信号转导抑制蛋白（Socs）家族蛋白），其中一些具有抗凋亡特性。我们发现，LIF处理可诱导c-Fos、c-Jun和JunB的表达，而JunD、酪氨酸磷酸酶ESP以及LIF受体的组分的表达则不受影响。在LIF存在的情况下，Socs-3的表达受到刺激，但Socs-1或Socs-2的表达未受影响。最后，Socs-1和Socs-3的不受控过表达导致LIF依赖性转录受到抑制，并严重降低细胞活力，这表明Socs蛋白含量的平衡失调对细胞存活具有不利影响。
