Gene Expression Profiling of Embryo-Derived Stem Cells Reveals Candidate Genes Associated With Pluripotency and Lineage Specificity
- Tetsuya S. Tanaka1,
- Tilo Kunath2,
- Wendy L. Kimber1,
- Saied A. Jaradat1,
- Carole A. Stagg1,
- Masayuki Usuda3,
- Takashi Yokota3,
- Hitoshi Niwa4,
- Janet Rossant2, and
- Minoru S.H. Ko1,5
- 1Laboratory of Genetics, National Institute on Aging, National Institutes of Health, Baltimore, Maryland, 21224-6820, USA; 2Samuel Lunenfeld Research Institute, Mount Sinai Hospital, University of Toronto, Toronto, Ontario, Canada; 3Department of Stem Cell Regulation, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan; 4Laboratory for Pluripotent Cell Studies, RIKEN Center for Developmental Biology, Kobe, Hyogo, Japan
Abstract
Large-scale gene expression profiling was performed on embryo-derived stem cell lines to identify molecular signatures of pluripotency and lineage specificity. Analysis of pluripotent embryonic stem (ES) cells, extraembryonic-restricted trophoblast stem (TS) cells, and terminally-differentiated mouse embryo fibroblast (MEF) cells identified expression profiles unique to each cell type, as well as genes common only to ES and TS cells. Whereas most of the MEF-specific genes had been characterized previously, the majority (67%) of the ES-specific genes were novel and did not include known differentiated cell markers. Comparison with microarray data from embryonic material demonstrated that ES-specific genes were underrepresented in all stages sampled, whereas TS-specific genes included known placental markers. Investigation of four novel TS-specific genes showed trophoblast-restricted expression in cell lines and in vivo, whereas one uncharacterized ES-specific gene, Esg-1, was found to be exclusively associated with pluripotency. We suggest that pluripotency requires a set of genes not expressed in other cell types, whereas lineage-restricted stem cells, like TS cells, express genes predictive of their differentiated lineage.
[Supplemental material is available online at www.genome.org andhttp://lgsun.grc.nia.nih.gov/microarray/data.html]
Footnotes
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↵5 Corresponding author.
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E-MAIL KoM{at}grc.nia.nih.gov; FAX (410) 558-8331.
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Article and publication are at http://www.genome.org/cgi/doi/10.1101/gr.670002.
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- Received July 30, 2002.
- Accepted October 7, 2002.
- Cold Spring Harbor Laboratory Press