G1 cyclins link proliferation, pluripotency and differentiation of embryonic stem cells

Nat Cell Biol. 2017 Mar;19(3):177-188. doi: 10.1038/ncb3474. Epub 2017 Feb 13.


Progression of mammalian cells through the G1 and S phases of the cell cycle is driven by the D-type and E-type cyclins. According to the current models, at least one of these cyclin families must be present to allow cell proliferation. Here, we show that several cell types can proliferate in the absence of all G1 cyclins. However, following ablation of G1 cyclins, embryonic stem (ES) cells attenuated their pluripotent characteristics, with the majority of cells acquiring the trophectodermal cell fate. We established that G1 cyclins, together with their associated cyclin-dependent kinases (CDKs), phosphorylate and stabilize the core pluripotency factors Nanog, Sox2 and Oct4. Treatment of murine ES cells, patient-derived glioblastoma tumour-initiating cells, or triple-negative breast cancer cells with a CDK inhibitor strongly decreased Sox2 and Oct4 levels. Our findings suggest that CDK inhibition might represent an attractive therapeutic strategy by targeting glioblastoma tumour-initiating cells, which depend on Sox2 to maintain their tumorigenic potential.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Biomarkers / metabolism
  • Cell Cycle
  • Cell Differentiation*
  • Cell Proliferation
  • Cell Separation
  • Cyclin G1 / metabolism*
  • DNA / analysis
  • Embryo, Mammalian / cytology
  • Epigenesis, Genetic
  • Female
  • Flow Cytometry
  • Gene Expression Profiling
  • Histones / metabolism
  • Hormones / pharmacology
  • Imaging, Three-Dimensional
  • Lysine / metabolism
  • Mammary Glands, Animal / cytology
  • Mammary Glands, Animal / embryology
  • Methylation
  • Mice
  • Mice, Inbred C57BL
  • Mouse Embryonic Stem Cells / cytology*
  • Mouse Embryonic Stem Cells / metabolism*
  • RNA / analysis
  • Receptors, G-Protein-Coupled / metabolism
  • Steroids / pharmacology
  • Tetraspanins / metabolism


  • Biomarkers
  • Cyclin G1
  • Histones
  • Hormones
  • Lgr5 protein, mouse
  • Receptors, G-Protein-Coupled
  • Steroids
  • Tetraspanins
  • RNA
  • DNA
  • Lysine