Akagi Tadayuki, Usuda Masayuki, Matsuda Takahiko, Ko Minoru S H, Niwa Hitoshi, Asano Masahide, Koide Hiroshi, Yokota Takashi
Department of Stem Cell Biology, Graduate School of Medical Science, Kanazawa University, 13-1 Takara-machi, Kanazawa, Ishikawa 920-8640, Japan.
Biochem Biophys Res Commun. 2005 May 27;331(1):23-30. doi: 10.1016/j.bbrc.2005.03.118.
Embryonic stem (ES) cells are pluripotent cells derived from the inner cell mass of blastocysts. Transcription factor STAT3 is essential for the self-renewal of ES cells. In this study, we searched for downstream molecules of STAT3 in ES cells. Using DNA chip analysis, we obtained zinc finger protein (Zfp)-57. The expression of Zfp-57 was restricted to undifferentiated ES cells and activation of STAT3 led to expression of Zfp-57. We also found that forced expression of a dominant-negative mutant of STAT3 or repression of Oct-3/4 expression led to down-regulation of Zfp-57. Targeted disruption of Zfp-57 resulted in no gross phenotypical defects, including expression of undifferentiated-state-specific genes. These data suggest that Zfp-57 is a downstream molecule of STAT3 and Oct-3/4 in ES cells, although dispensable for their self-renewal.
胚胎干细胞(ES细胞)是源自囊胚内细胞团的多能细胞。转录因子STAT3对ES细胞的自我更新至关重要。在本研究中,我们在ES细胞中寻找STAT3的下游分子。通过DNA芯片分析,我们获得了锌指蛋白(Zfp)-57。Zfp-57的表达仅限于未分化的ES细胞,并且STAT3的激活导致Zfp-57的表达。我们还发现,强制表达STAT3的显性负性突变体或抑制Oct-3/4的表达会导致Zfp-57的下调。Zfp-57的靶向破坏未导致明显的表型缺陷,包括未分化状态特异性基因的表达。这些数据表明,Zfp-57是ES细胞中STAT3和Oct-3/4的下游分子,尽管对它们的自我更新并非必需。