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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: 2007-0893v1 2007-0893v2 2007-0893v3 26/4/927    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 Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Orwig, K. E. Articles by Brinster, R. L. Search for Related Content PubMed PubMed Citation Articles by Orwig, K. E. Articles by Brinster, R. L.

STEM CELL GENOMICS AND PROTEOMICS

Genes Involved in Post-Transcriptional Regulation Are Overrepresented in Stem/Progenitor Spermatogonia of Cryptorchid Mouse Testes

Departments of ^aObstetrics, Gynecology and Reproductive Sciences and
^bMolecular Genetics and Biochemistry, Magee-Womens Research Institute, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA;
^cDepartment of Animal Biology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA;
Departments of ^dCancer Biology, Abramson Family Cancer Research Institute, and
^fMedicine, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, USA;
^eDepartment of Internal Medicine, University of Regensburg, Regensburg, Germany

Key Words. Spermatogonial stem cell • Progenitor • Spermatogonia • Microarray • RNA-binding proteins • Post-transcriptional regulation

Correspondence: Ralph L. Brinster, V.M.D., Ph.D., Department of Animal Biology, School of Veterinary Medicine, University of Pennsylvania, 3850 Baltimore Avenue, Philadelphia, Pennsylvania 19104, USA. Telephone: 215-898-8805; Fax: 215-898-0667; e-mail: cpope{at}vet.upenn.edu

Received October 24, 2007; accepted for publication January 9, 2008.
First published online in STEM CELLS EXPRESS   January 17, 2008.



Gene expression and consequent biological activity of adult tissue stem cells are regulated by signals emanating from the local microenvironment (niche). To gain insights into the molecular regulation of spermatogonial stem cells (SSCs), gene expression was characterized from SSCs isolated from their cognate niches of cryptorchid (stem cell-enriched), wild-type, and busulfan-treated (stem cell-depleted) mouse testes. Quantitative assessment of stem cell activity in each testis model was determined using an in vivo functional assay and correlated with gene expression using Affymetrix MGU74Av2 microarrays and the ChipStat algorithm optimized to detect gene expression from rare cells in complex tissues. We identified 389 stem/progenitor spermatogonia candidate genes, which exhibited significant overlap with genes expressed by embryonic, hematopoietic, and neural stem cells; enriched spermatogonia; and cultured SSCs identified in previous studies. Candidate cell surface markers identified by the microarray may facilitate the isolation and enrichment of stem and/or progenitor spermatogonia. Flow cytometric analyses confirmed the expression of chemokine receptor 2 (Ccr2) and Cd14 on a subpopulation cryptorchid testis cells (6-integrin⁺, side scatter^lo) enriched for SSCs. These cell surface molecules may mark progenitor spermatogonia but not SSCs because Ccr2⁺ and Cd14⁺ fractions failed to produce spermatogenesis upon transplantation to recipient testes. Functional annotation of candidate genes and subsequent immunohistochemistry revealed that proteins involved in post-transcriptional regulation are overrepresented in cryptorchid testes that are enriched for SSCs. Comparative analyses indicated that this is a recurrent biological theme among stem cells.

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