Molecular ties between the cell cycle and differentiation in embryonic stem cells

Proc Natl Acad Sci U S A. 2014 Jul 1;111(26):9503-8. doi: 10.1073/pnas.1408638111. Epub 2014 Jun 16.

Abstract

Attainment of the differentiated state during the final stages of somatic cell differentiation is closely tied to cell cycle progression. Much less is known about the role of the cell cycle at very early stages of embryonic development. Here, we show that molecular pathways involving the cell cycle can be engineered to strongly affect embryonic stem cell differentiation at early stages in vitro. Strategies based on perturbing these pathways can shorten the rate and simplify the lineage path of ES differentiation. These results make it likely that pathways involving cell proliferation intersect at various points with pathways that regulate cell lineages in embryos and demonstrate that this knowledge can be used profitably to guide the path and effectiveness of cell differentiation of pluripotent cells.

Keywords: differentiation modeling; guided differentiation; proliferation control; systems biology.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Cell Cycle / physiology*
  • Cell Differentiation / physiology*
  • Chromones
  • Cloning, Molecular
  • DNA Primers / genetics
  • Embryonic Development / physiology*
  • Embryonic Stem Cells / physiology*
  • Flavonoids
  • MAP Kinase Kinase 1 / antagonists & inhibitors
  • Mice
  • Microarray Analysis
  • Morpholines
  • Muscle, Skeletal / cytology
  • Muscle, Skeletal / physiology*
  • Phosphoinositide-3 Kinase Inhibitors
  • Plasmids / genetics
  • Purines
  • Reverse Transcriptase Polymerase Chain Reaction
  • Roscovitine

Substances

  • Chromones
  • DNA Primers
  • Flavonoids
  • Morpholines
  • Phosphoinositide-3 Kinase Inhibitors
  • Purines
  • Roscovitine
  • 2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one
  • MAP Kinase Kinase 1
  • 2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one