The essentiality landscape of cell cycle related genes in human pluripotent and cancer cells.
Bioinformatics
CRISPR/Cas9 libraries
Cancer
Cell cycle
Checkpoints
Embryonic stem cells
TP53
Journal
Cell division
ISSN: 1747-1028
Titre abrégé: Cell Div
Pays: England
ID NLM: 101251560
Informations de publication
Date de publication:
2019
2019
Historique:
received:
08
10
2019
accepted:
06
12
2019
entrez:
1
1
2020
pubmed:
1
1
2020
medline:
1
1
2020
Statut:
epublish
Résumé
Cell cycle regulation is a complex system consisting of growth-promoting and growth-restricting mechanisms, whose coordinated activity is vital for proper division and propagation. Alterations in this regulation may lead to uncontrolled proliferation and genomic instability, triggering carcinogenesis. Here, we conducted a comprehensive bioinformatic analysis of cell cycle-related genes using data from CRISPR/Cas9 loss-of-function screens performed in four cancer cell lines and in human embryonic stem cells (hESCs). Cell cycle genes, and in particular S phase and checkpoint genes, are highly essential for the growth of cancer and pluripotent cells. However, checkpoint genes are also found to underlie the differences between the cell cycle features of these cell types. Interestingly, while growth-promoting cell cycle genes overlap considerably between cancer and stem cells, growth-restricting cell cycle genes are completely distinct. Moreover, growth-restricting genes are consistently less frequent in cancer cells than in hESCs. Here we show that most of these genes are regulated by the tumor suppressor gene Our results highlight the differences in cell cycle regulation between cell types and emphasize the importance of conducting cell cycle studies in cells with intact genomes, in order to obtain an authentic representation of the genetic features of the cell cycle.
Sections du résumé
BACKGROUND
BACKGROUND
Cell cycle regulation is a complex system consisting of growth-promoting and growth-restricting mechanisms, whose coordinated activity is vital for proper division and propagation. Alterations in this regulation may lead to uncontrolled proliferation and genomic instability, triggering carcinogenesis. Here, we conducted a comprehensive bioinformatic analysis of cell cycle-related genes using data from CRISPR/Cas9 loss-of-function screens performed in four cancer cell lines and in human embryonic stem cells (hESCs).
RESULTS
RESULTS
Cell cycle genes, and in particular S phase and checkpoint genes, are highly essential for the growth of cancer and pluripotent cells. However, checkpoint genes are also found to underlie the differences between the cell cycle features of these cell types. Interestingly, while growth-promoting cell cycle genes overlap considerably between cancer and stem cells, growth-restricting cell cycle genes are completely distinct. Moreover, growth-restricting genes are consistently less frequent in cancer cells than in hESCs. Here we show that most of these genes are regulated by the tumor suppressor gene
CONCLUSIONS
CONCLUSIONS
Our results highlight the differences in cell cycle regulation between cell types and emphasize the importance of conducting cell cycle studies in cells with intact genomes, in order to obtain an authentic representation of the genetic features of the cell cycle.
Identifiants
pubmed: 31889988
doi: 10.1186/s13008-019-0058-4
pii: 58
pmc: PMC6927170
doi:
Types de publication
Journal Article
Langues
eng
Pagination
15Informations de copyright
© The Author(s) 2019.
Déclaration de conflit d'intérêts
Competing interestsNB. is CSO of NewStem Ltd.
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