Institute of Molecular Medicine, National Tsing Hua University, 101, Section 2, Kuang-Fu Road, Hsinchu 30013, Taiwan.
Int J Biochem Cell Biol. 2012 Feb;44(2):350-7. doi: 10.1016/j.biocel.2011.11.008. Epub 2011 Nov 17.
UTF1 (undifferentiated embryonic cell transcription factor 1) is a marker for the pluripotency of embryonic stem cells. We found that UTF1-deficient clones, which were isolated from P19 embryonal carcinoma (EC) cells, showed higher neuron-differentiating potentials than the parental cell line. Consistent with this result, suppression of UTF1 expression in P19 cells by RNA interference enhanced retinoic acid (RA)-induced neuronal differentiation. Moreover, reconstitution of UTF1 expression in UTF1-deficient clones decreased their ability to undergo neuronal differentiation. Interestingly, the growth rates of UTF1-deficient P19 cells did not differ from that of parental cells in adherent cultures, but were increased in embryoid bodies during RA-induced differentiation. Furthermore, different from the parental cells, UTF1-deficient P19 clones could proceed to neuronal differentiation without forming embryoid bodies. Based on these results we proposed that endogenous UTF1 prevented P19 EC cells from neuronal differentiation, and that the loss of UTF1 directed EC cells toward the neuronal fate.
UTF1（未分化胚胎细胞转录因子 1）是胚胎干细胞多能性的标志物。我们发现，从 P19 胚胎癌细胞中分离出的 UTF1 缺陷克隆比亲本细胞系具有更高的神经元分化潜力。与这一结果一致，通过 RNA 干扰抑制 P19 细胞中的 UTF1 表达增强了视黄酸（RA）诱导的神经元分化。此外，在 UTF1 缺陷克隆中重建 UTF1 表达降低了它们进行神经元分化的能力。有趣的是，UTF1 缺陷型 P19 细胞在贴壁培养中的生长速度与亲本细胞没有差异，但在 RA 诱导分化过程中的胚状体中增加。此外，与亲本细胞不同的是，UTF1 缺陷型 P19 克隆可以在不形成胚状体的情况下进行神经元分化。基于这些结果，我们提出内源性 UTF1 阻止 P19 EC 细胞向神经元分化，而 UTF1 的缺失将 EC 细胞定向为神经元命运。
