4.8 Article

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

期刊

CELL REPORTS
卷 34, 期 13, 页码 -

出版社

CELL PRESS
DOI: 10.1016/j.celrep.2021.108903

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资金

  1. Ontario Graduate Scholarships from the University of Toronto
  2. Ontario Institute for Cancer Research (OICR) TRI grant BCTRI-FR-HSK
  3. OICR Investigator grant [IA-026]
  4. OICR TRI grant BC-TRI-FR-HSK
  5. Canadian Institutes of Health Research (CIHR) project [PJT-159611]
  6. CIHR [MOP-142267, PJT-377122, PJT-406569]
  7. Restracomp scholarship from the Hospital for Sick Children
  8. SickKids Restracomp Fellowship from the Hospital for Sick Children
  9. Sontag Foundation
  10. Natural Sciences and Engineering Research Council (NSERC) Discovery Grant
  11. Ontario Graduate Scholarship from the University of Toronto
  12. Stand Up To Cancer (SU2C) Canada Cancer Stem Cell Dream Team [SU2C-AACR-DT-19-15]
  13. Canada Research Chair in Translational Genomics
  14. Senior Investigator Award from the OICR
  15. Canada Foundation for Innovation (CFI) Leaders Opportunity Fund [32383]
  16. Government of Canada through Genome Canada [SU2C-AACR-DT-19-15]
  17. CIHR
  18. OICR by Government of Ontario
  19. American Association for Cancer Research International-Canada, the scientific partner of SU2C Canada

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By using a comparative genomics approach, researchers have identified and demonstrated the role of DEAD-box helicase DDX56 in regulating stemness in different cell systems. DDX56 affects ribosomal RNA expression and nucleolar integrity in planarians, mouse neural stem cells, human GSCs, and a fruit fly model, ultimately leading to stem cell death.
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.

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