1. Center for Regenerative Medicine, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, California 92037, USA
2. Center for Psychiatry, ZIP-Kiel, University Hospital Schleswig Holstein, Niemannsweg 147, D-24105 Kiel, Germany
3. University of California, San Diego, Department of Reproductive Medicine, 200 West Arbor Drive, San Diego, California 92035, USA
4. Department of Computational Molecular Biology, Max Planck Institute for Molecular Genetics, Ihnestrasse 63-73, D-14195 Berlin, Germany
5. School of Computer Science, Tel Aviv University, Tel Aviv 69978, Israel
6. The Burnham Institute for Medical Research, 10901 North Torrey Pines Road, La Jolla, California 92037, USA
7. Division of Pediatric Hematology/Oncology, Children's Hospital Boston and Dana Farber Cancer Institute, Boston, Massachusetts 02115, USA
8. Invitrogen Co, 3705 Executive Way, Frederick, Maryland 21704, USA
9. Center for Stem Cell Biology, Buck Institute on Aging, 8001 Redwood Boulevard, Novato, California 94945, USA
10. Center for Neuroscience Research, Children's Hospital of Orange County Research Institute, 455 South Main Street, Orange, California 92868, USA
11. Developmental Biology Center, University of California, Irvine, 4205 McGaugh Hall, Irvine, California 92697, USA
12. Department for Neurosurgery University Medical Center Hamburg-Eppendorf, Martinistrasse 52, D-20246 Hamburg, Germany
13. Present address: Genome and Biomedical Sciences Facility and Department of Statistics, University of California, Davis 451 Health Sciences Drive, Davis, California 95616, USA.

Correspondence to: Franz-Josef Müller^1,2Jeanne F. Loring^1,6 Correspondence and requests for materials should be addressed to F.-J.M. (Email: fj.mueller@zip-kiel.de) or J.F.L. (Email: jloring@scripps.edu).

Abstract

Stem cells are defined as self-renewing cell populations that can differentiate into multiple distinct cell types. However, hundreds of different human cell lines from embryonic, fetal and adult sources have been called stem cells, even though they range from pluripotent cells—typified by embryonic stem cells, which are capable of virtually unlimited proliferation and differentiation—to adult stem cell lines, which can generate a far more limited repertoire of differentiated cell types. The rapid increase in reports of new sources of stem cells and their anticipated value to regenerative medicine^{1, 2} has highlighted the need for a general, reproducible method for classification of these cells³. We report here the creation and analysis of a database of global gene expression profiles (which we call the 'stem cell matrix') that enables the classification of cultured human stem cells in the context of a wide variety of pluripotent, multipotent and differentiated cell types. Using an unsupervised clustering method^{4, 5} to categorize a collection of 150 cell samples, we discovered that pluripotent stem cell lines group together, whereas other cell types, including brain-derived neural stem cell lines, are very diverse. Using further bioinformatic analysis⁶ we uncovered a protein–protein network (PluriNet) that is shared by the pluripotent cells (embryonic stem cells, embryonal carcinomas and induced pluripotent cells). Analysis of published data showed that the PluriNet seems to be a common characteristic of pluripotent cells, including mouse embryonic stem and induced pluripotent cells and human oocytes. Our results offer a new strategy for classifying stem cells and support the idea that pluripotency and self-renewal are under tight control by specific molecular networks.

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