Journal Article

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 and Minoru S. H. Ko

in DNA Research

Published on behalf of Kazusa DNA Research Institute

Volume 16, issue 1, pages 73-80
Published in print February 2009 | ISSN: 1340-2838
Published online December 2008 | e-ISSN: 1756-1663 | DOI: http://dx.doi.org/10.1093/dnares/dsn035

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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.

Keywords: embryonic stem; embryonic germ; induced pluripotent stem; mouse embryo fibroblast; embryonal carcinoma; retinoic acids; neural stem/progenitor; trophoblast stem; principal component analysis; leukemia inhibitory factor; epigenetic landscape; Waddington; developmental potency; cell lineage trajectory; gene expression profiling; DNA microarray analysis

Journal Article.  3827 words.  Illustrated.

Subjects: Genetics and Genomics

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