The nature of embryonic stem cells

Annu Rev Cell Dev Biol. 2014;30:647-75. doi: 10.1146/annurev-cellbio-100913-013116.


Mouse embryonic stem (ES) cells perpetuate in vitro the broad developmental potential of naïve founder cells in the preimplantation embryo. ES cells self-renew relentlessly in culture but can reenter embryonic development seamlessly, differentiating on schedule to form all elements of the fetus. Here we review the properties of these remarkable cells. Arising from the stability, homogeneity, and equipotency of ES cells, we consider the concept of a pluripotent ground state. We evaluate the authenticity of ES cells in relation to cells in the embryo and examine their utility for dissecting mechanisms that confer pluripotency and that execute fate choice. We summarize current knowledge of the transcription factor circuitry that governs the ES cell state and discuss the opportunity to expose molecular logic further through iterative computational modeling and experimentation. Finally, we present a perspective on unresolved questions, including the challenge of deriving ground state pluripotent stem cells from non-rodent species.

Keywords: commitment; gene regulatory network; mammalian development; pluripotency; self-renewal; transcription factors.

Publication types

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

MeSH terms

  • Animals
  • Asymmetric Cell Division
  • Blastocyst / cytology
  • Cell Culture Techniques
  • Cell Lineage
  • Cells, Cultured
  • Cellular Reprogramming
  • Coculture Techniques
  • Culture Media
  • Culture Media, Serum-Free
  • Embryonal Carcinoma Stem Cells / cytology
  • Embryonic Stem Cells / cytology*
  • Embryonic Stem Cells / physiology
  • Fibroblasts / cytology
  • Gene Expression Profiling
  • Gene Expression Regulation, Developmental
  • Genes, Reporter
  • Germ Layers / cytology
  • Humans
  • Intercellular Signaling Peptides and Proteins / pharmacology
  • Intercellular Signaling Peptides and Proteins / physiology
  • Leukemia Inhibitory Factor / physiology
  • Mice
  • Pluripotent Stem Cells / cytology
  • Pluripotent Stem Cells / physiology
  • Transcription Factors / pharmacology
  • Transcription Factors / physiology


  • Culture Media
  • Culture Media, Serum-Free
  • Intercellular Signaling Peptides and Proteins
  • Leukemia Inhibitory Factor
  • Lif protein, mouse
  • Transcription Factors