Journal
CELL REPORTS
Volume 34, Issue 13, Pages -Publisher
CELL PRESS
DOI: 10.1016/j.celrep.2021.108903
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Funding
- Ontario Graduate Scholarships from the University of Toronto
- Ontario Institute for Cancer Research (OICR) TRI grant BCTRI-FR-HSK
- OICR Investigator grant [IA-026]
- OICR TRI grant BC-TRI-FR-HSK
- Canadian Institutes of Health Research (CIHR) project [PJT-159611]
- CIHR [MOP-142267, PJT-377122, PJT-406569]
- Restracomp scholarship from the Hospital for Sick Children
- SickKids Restracomp Fellowship from the Hospital for Sick Children
- Sontag Foundation
- Natural Sciences and Engineering Research Council (NSERC) Discovery Grant
- Ontario Graduate Scholarship from the University of Toronto
- Stand Up To Cancer (SU2C) Canada Cancer Stem Cell Dream Team [SU2C-AACR-DT-19-15]
- Canada Research Chair in Translational Genomics
- Senior Investigator Award from the OICR
- Canada Foundation for Innovation (CFI) Leaders Opportunity Fund [32383]
- Government of Canada through Genome Canada [SU2C-AACR-DT-19-15]
- CIHR
- OICR by Government of Ontario
- 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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