Defining developmental potency and cell lineage trajectories by expression profiling of differentiating mouse embryonic stem cells

Kazuhiro Aiba, Timur Nedorezov, Yulan Piao, Akira Nishiyama, Ryo Matoba, Lioudmila V. Sharova, Alexei A. Sharov, Shinya Yamanaka, Hitoshi Niwa, Minoru S.H. Ko

Research output: Contribution to journalArticlepeer-review

38 Citations (Scopus)


Biologists rely on morphology, function and specific markers to define the differentiation status of cells. Transcript profiling has expanded the repertoire of these markers by providing the snapshot of cellular status that reflects the activity of all genes. However, such data have been used only to assess relative similarities and differences of these cells. Here we show that principal component analysis of global gene expression profiles map cells in multidimensional transcript profile space and the positions of differentiating cells progress in a stepwise manner along trajectories starting from undifferentiated embryonic stem (ES) cells located in the apex. We present three 'cell lineage trajectories', which represent the differentiation of ES cells into the first three lineages in mammalian development: primitive endoderm, trophoblast and primitive ectoderm/neural ectoderm. The positions of the cells along these trajectories seem to reflect the developmental potency of cells and can be used as a scale for the potential of cells. Indeed, we show that embryonic germ cells and induced pluripotent cells are mapped near the origin of the trajectories, whereas mouse embryo fibroblast and fibroblast cell lines are mapped near the far end of the trajectories. We suggest that this method can be used as the non-operational semi-quantitative definition of cell differentiation status and developmental potency. Furthermore, the global expression profiles of cell lineages provide a framework for the future study of in vitro and in vivo cell differentiation.

Original languageEnglish
Pages (from-to)73-80
Number of pages8
JournalDNA Research
Issue number1
Publication statusPublished - 2009 Feb
Externally publishedYes


  • Embryonal carcinoma
  • Embryonic germ
  • Embryonic stem
  • Epigenetic landscape
  • Induced pluripotent stem
  • Leukemia inhibitory factor
  • Mouse embryo fibroblast
  • Neural stem/progenitor
  • Principal component analysis
  • Retinoic acids
  • Trophoblast stem
  • Waddington

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics


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