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Comparative transcriptome analysis of embryonic and adult stem cells with extended and limited differentiation capacity

Fernando Ulloa-Montoya123, Benjamin L Kidder1, Karen A Pauwelyn13, Lucas G Chase1, Aernout Luttun13, Annelies Crabbe3, Martine Geraerts3, Alexei A Sharov4, Yulan Piao4, Minoru SH Ko4, Wei-Shou Hu2 and Catherine M Verfaillie13*

Author affiliations

1 Stem Cell Institute, University of Minnesota, Minneapolis, MN 55455, USA

2 Department of Chemical Engineering and Materials Science, University of Minnesota, Minneapolis, MN 55455, USA

3 Stamcel Instituut, Katholieke Universiteit Leuven, Leuven 3000, Belgium

4 Developmental Genomics and Aging Section, Laboratory of Genetics, National Institute on Aging, NIH, Baltimore, MD 21224, USA

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Citation and License

Genome Biology 2007, 8:R163  doi:10.1186/gb-2007-8-8-r163

Published: 6 August 2007

Abstract

Background

Recently, several populations of postnatal stem cells, such as multipotent adult progenitor cells (MAPCs), have been described that have broader differentiation ability than classical adult stem cells. Here we compare the transcriptome of pluripotent embryonic stem cells (ESCs), MAPCs, and lineage-restricted mesenchymal stem cells (MSCs) to determine their relationship.

Results

Applying principal component analysis, non-negative matrix factorization and k-means clustering algorithms to the gene-expression data, we identified a unique gene-expression profile for MAPCs. Apart from the ESC-specific transcription factor Oct4 and other ESC transcripts, some of them associated with maintaining ESC pluripotency, MAPCs also express transcripts characteristic of early endoderm and mesoderm. MAPCs do not, however, express Nanog or Sox2, two other key transcription factors involved in maintaining ESC properties. This unique molecular signature was seen irrespective of the microarray platform used and was very similar for both mouse and rat MAPCs. As MSC-like cells isolated under MAPC conditions are virtually identical to MSCs, and MSCs cultured in MAPC conditions do not upregulate MAPC-expressed transcripts, the MAPC signature is cell-type specific and not merely the result of differing culture conditions.

Conclusion

Multivariate analysis techniques clustered stem cells on the basis of their expressed gene profile, and the genes determining this clustering reflected the stem cells' differentiation potential in vitro. This comparative transcriptome analysis should significantly aid the isolation and culture of MAPCs and MAPC-like cells, and form the basis for studies to gain insights into genes that confer on these cells their greater developmental potency.