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

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


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.

Keywords: DDX56; RNAi; adult stem cells; cancer stem cells; comparative genomics; evolution of stem cells; glioblastoma; planarians; stemness.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult Stem Cells / metabolism
  • Animals
  • Cell Line, Tumor
  • Cell Lineage
  • Cell Nucleolus / metabolism
  • Cell Proliferation
  • Cell Self Renewal
  • Cell Survival
  • Cerebral Cortex / cytology
  • DEAD-box RNA Helicases / genetics
  • DEAD-box RNA Helicases / metabolism*
  • Drosophila / metabolism
  • Drosophila Proteins / metabolism
  • Gene Expression Regulation, Neoplastic
  • Genomics
  • Glioblastoma / genetics
  • Glioblastoma / pathology
  • HEK293 Cells
  • Humans
  • Mice
  • Models, Biological
  • Neoplastic Stem Cells / metabolism*
  • Neoplastic Stem Cells / pathology
  • Neural Stem Cells / metabolism
  • Planarians / cytology
  • Planarians / metabolism
  • RNA Interference
  • Ribosome Subunits / metabolism
  • Treatment Outcome
  • Up-Regulation / genetics


  • Drosophila Proteins
  • DDX56 protein, human
  • DEAD-box RNA Helicases