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This Article Free via Open Access: OA OA Full Text Full Text (PDF) Supplemental Data OA All Versions of this Article: 2007-1081v1 26/6/1506    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Reprints/Permissions Google Scholar Articles by Laurent, L. C. Articles by Loring, J. F. PubMed PubMed Citation Articles by Laurent, L. C. Articles by Loring, J. F.

EMBRYONIC STEM CELLS

Comprehensive MicroRNA Profiling Reveals a Unique Human Embryonic Stem Cell Signature Dominated by a Single Seed Sequence

^aDepartment of Reproductive Medicine, University of California San Diego, San Diego, California, USA;
^bThe Scripps Research Institute, La Jolla, California, USA;
^cIllumina, Inc., San Diego, California, USA;
^dSchool of Computer Science, Tel Aviv University, Tel Aviv, Israel;
^eZentrum für Integrative Psychiatrie, Universitätsklinikums Schleswig-Holstein, Kiel, Germany

Key Words. Embryonic stem cells • Adult stem cells • MicroRNA • Oligonucleotide microarray • Gene expression profiling

Correspondence: Louise C. Laurent, M.D., Ph.D., The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, California 92037, USA. Telephone: 858-784-7135; Fax: 858-784-7211; e-mail: llaurent{at}ucsd.edu; or Jeanne F. Loring, Ph.D., The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, California 92037, USA. Telephone: 858-784-7767; Fax: 858-784-7211; e-mail: jloring{at}scripps.edu

Received January 4, 2008; accepted for publication March 20, 2008.
First published online in STEM CELLS EXPRESS   April 10, 2008.



Embryonic stem cells are unique among cultured cells in their ability to self-renew and differentiate into a wide diversity of cell types, suggesting that a specific molecular control network underlies these features. Human embryonic stem cells (hESCs) are known to have distinct mRNA expression, global DNA methylation, and chromatin profiles, but the involvement of high-level regulators, such as microRNAs (miRNA), in the hESC-specific molecular network is poorly understood. We report that global miRNA expression profiling of hESCs and a variety of stem cell and differentiated cell types using a novel microarray platform revealed a unique set of miRNAs differentially regulated in hESCs, including numerous miRNAs not previously linked to hESCs. These hESC-associated miRNAs were more likely to be located in large genomic clusters, and less likely to be located in introns of coding genes. hESCs had higher expression of oncogenic miRNAs and lower expression of tumor suppressor miRNAs than the other cell types. Many miRNAs upregulated in hESCs share a common consensus seed sequence, suggesting that there is cooperative regulation of a critical set of target miRNAs. We propose that miRNAs are coordinately controlled in hESCs, and are key regulators of pluripotence and differentiation.

Disclosure of potential conflicts of interest is found at the end of this article.