Now Hesung, Yoo Joo-Yeon
Department of Life Sciences, Pohang University of Science and Technology (POSTECH), Pohang, 37673, Republic of Korea.
PLoS One. 2016 Jul 18;11(7):e0159453. doi: 10.1371/journal.pone.0159453. eCollection 2016.
A population often contains distinct sub-populations, thereby increasing the complexity of the overall heterogeneity. However, the cellular origin and biological relevance of sub-populations in cell population have not been clearly identified. Here we demonstrated the novel roles of ISGylation, which is an IFN-induced post-translational modification, controlling heterogeneity at the population level in cultured adherent cells. Without UBE1L, an E1 enzyme of ISGylation, mouse embryonic fibroblasts (MEF) exhibited low viral resistance despite high STAT1 and ISG expression compared with the wild-type MEF. We observe that Ube1l-/- MEF populations consist of two behaviorally distinguishable sub-populations with distinct basal STAT1 activity, while wild-type MEF populations are unimodal. This population heterogeneity in Ube1l knock-out cells was perturbed by tyrosine kinase inhibitors, AG490 and PF431396. In contrast, the neutralization of type I IFN did not affect population heterogeneity. Based on these results, we concluded that UBE1L functions to adjust basal immunological states with the regulation of population heterogeneity.
一个群体通常包含不同的亚群体，从而增加了整体异质性的复杂性。然而，细胞群体中亚群体的细胞起源和生物学相关性尚未明确确定。在这里，我们展示了ISGylation的新作用，它是一种干扰素诱导的翻译后修饰，在培养的贴壁细胞群体水平上控制异质性。没有ISGylation的E1酶UBE1L，小鼠胚胎成纤维细胞（MEF）尽管与野生型MEF相比STAT1和ISG表达较高，但仍表现出较低的病毒抗性。我们观察到，Ube1l-/-MEF群体由两个行为上可区分的亚群体组成，具有不同的基础STAT1活性，而野生型MEF群体是单峰的。Ube1l基因敲除细胞中的这种群体异质性受到酪氨酸激酶抑制剂AG490和PF431396的干扰。相反，I型干扰素的中和并不影响群体异质性。基于这些结果，我们得出结论，UBE1L通过调节群体异质性来调节基础免疫状态。
