Epigenetic dynamics of stem cells and cell lineage commitment: digging Waddington's canal

Nat Rev Mol Cell Biol. 2009 Aug;10(8):526-37. doi: 10.1038/nrm2727. Epub 2009 Jul 15.


Cells of the early mammalian embryo, including pluripotent embryonic stem (ES) cells and primordial germ cells (PGCs), are epigenetically dynamic and heterogeneous. During early development, this heterogeneity of epigenetic states is associated with stochastic expression of lineage-determining transcription factors that establish an intimate crosstalk with epigenetic modifiers. Lineage-specific epigenetic modification of crucial transcription factor loci (for example, methylation of the Elf5 promoter) leads to the restriction of transcriptional circuits and the fixation of lineage fate. The intersection of major epigenetic reprogramming and programming events in the early embryo creates plasticity followed by commitment to the principal cell lineages of the early conceptus.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Cell Lineage / genetics*
  • Epigenesis, Genetic*
  • Humans
  • Life Cycle Stages / genetics
  • Pluripotent Stem Cells / metabolism
  • Stem Cells / metabolism*