DEAD-box 解旋酶 DDX56 是正常和肿瘤干细胞中保守的干性调节因子。

The DEAD-box helicase DDX56 is a conserved stemness regulator in normal and cancer stem cells.

机构信息

The Hospital for Sick Children, Program in Developmental and Stem Cell Biology, Toronto, ON M5G 0A4, Canada; University of Toronto, Department of Molecular Genetics, Toronto, ON M5S 1A8, Canada.

The Hospital for Sick Children, Program in Developmental and Stem Cell Biology, Toronto, ON M5G 0A4, Canada.

出版信息

Cell Rep. 2021 Mar 30;34(13):108903. doi: 10.1016/j.celrep.2021.108903.

DOI:10.1016/j.celrep.2021.108903

PMID:33789112

Abstract

Across the animal kingdom, adult tissue homeostasis is regulated by adult stem cell activity, which is commonly dysregulated in human cancers. However, identifying key regulators of stem cells in the milieu of thousands of genes dysregulated in a given cancer is challenging. Here, using a comparative genomics approach between planarian adult stem cells and patient-derived glioblastoma stem cells (GSCs), we identify and demonstrate the role of DEAD-box helicase DDX56 in regulating aspects of stemness in four stem cell systems: planarians, mouse neural stem cells, human GSCs, and a fly model of glioblastoma. In a human GSC line, DDX56 localizes to the nucleolus, and using planarians, when DDX56 is lost, stem cells dysregulate expression of ribosomal RNAs and lose nucleolar integrity prior to stem cell death. Together, a comparative genomic approach can be used to uncover conserved stemness regulators that are functional in both normal and cancer stem cells.

摘要

在整个动物界，成体组织稳态由成体干细胞活性调节，而这种活性在人类癌症中经常失调。然而，在给定癌症中数千个失调基因的环境中识别干细胞的关键调节因子具有挑战性。在这里，我们使用秀丽隐杆线虫成体干细胞和患者来源的脑胶质瘤干细胞（GSCs）之间的比较基因组学方法，在四个干细胞系统中鉴定并证明了 DEAD-box 解旋酶 DDX56 在调节干性方面的作用：秀丽隐杆线虫、小鼠神经干细胞、人类 GSCs 和胶质母细胞瘤的果蝇模型。在人类 GSC 系中，DDX56 定位于核仁，并且使用秀丽隐杆线虫，当 DDX56 缺失时，干细胞在干细胞死亡之前会失调核糖体 RNA 的表达并失去核仁完整性。总之，比较基因组学方法可用于发现保守的干性调节因子，这些因子在正常和癌症干细胞中均具有功能。