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

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.
Michael Pryszlak 1,  Mallory Wiggans 1,  Xin Chen 2,  Julia E Jaramillo 1,  Sarah E Burns 2,  Laura M Richards 3,  Trevor J Pugh 4,  David R Kaplan 1,  Xi Huang 5,  Peter B Dirks 5,  Bret J Pearson 6
Affiliations

Affiliations

  • 1 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.
  • 2 The Hospital for Sick Children, Program in Developmental and Stem Cell Biology, Toronto, ON M5G 0A4, Canada.
  • 3 Department of Medical Biophysics, University of Toronto, ON M5G 1L7, Canada; Princess Margaret Cancer Centre, University Health Network, Toronto, ON M5G 2C1, Canada.
  • 4 Ontario Institute for Cancer Research, Toronto, ON M5G 0A3, Canada; Department of Medical Biophysics, University of Toronto, ON M5G 1L7, Canada; Princess Margaret Cancer Centre, University Health Network, Toronto, ON M5G 2C1, Canada.
  • 5 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; Ontario Institute for Cancer Research, Toronto, ON M5G 0A3, Canada; The Hospital for Sick Children, Arthur and Sonia Labatt Brain Tumor Research Centre, Toronto, ON M5G 0A4, Canada.
  • 6 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; Ontario Institute for Cancer Research, Toronto, ON M5G 0A3, Canada. Electronic address: bret.pearson@sickkids.ca.
PMID: 33789112 DOI: 10.1016/j.celrep.2021.108903
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.

Keywords

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

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