HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Supplemental Data All Versions of this Article: 2008-0506v1 26/12/3237    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 Ohmura, M. Articles by Hirao, A. Search for Related Content PubMed PubMed Citation Articles by Ohmura, M. Articles by Hirao, A.

TISSUE-SPECIFIC STEM CELLS

Identification of Stem Cells During Prepubertal Spermatogenesis via Monitoring of Nucleostemin Promoter Activity

^aDivision of Molecular Genetics, Center for Cancer and Stem Cell Research, Cancer Research Institute, Kanazawa University, Kanazawa, Ishikawa, Japan;
^bDepartment of Anatomy, Division of Functional Morphology, Dental Research Center, Nihon University School of Dentistry, Chiyoda-ku, Japan;
^cCore Research for Evolutional Science and Technology (CREST), Japan Science and Technology Agency, Chiyoda-ku, Tokyo, Japan;
^dDepartment of Cell Differentiation, The Sakaguchi Laboratory of Developmental Biology, Keio University School of Medicine, Shinjuku-ku, Tokyo, Japan;
^eDepartment of Safety Research on Blood and Biological Products, National Institute of Infectious Diseases, Musashimurayama, Tokyo, Japan;
^fKyowa Hakko BioFrontier Laboratories, Machida, Tokyo, Japan

Key Words. Nucleostemin • Spermatogenesis • Stem cells • Transplantation

Correspondence: Correspondence: Atsushi Hirao, M.D., Division of Molecular Genetics, Center for Cancer and Stem Cell Research, Cancer Research Institute, Kanazawa University, 13-1 Takaramachi, Kanazawa, Ishikawa 920-0934, Japan. Telephone: 81-76-265-2726; Fax: 81-76-234-4508; e-mail: ahirao{at}kenroku.kanazawa-u.ac.jp

Received on May 23, 2008; accepted for publication on September 8, 2008.

First published online in STEM CELLS EXPRESS  September 18, 2008.

The nucleostemin (NS) gene encodes a nucleolar protein found at high levels in several types of stem cells and tumor cell lines. The function of NS is unclear but it may play a critical role in S-phase entry by stem/progenitor cells. Here we characterize NS expression in murine male germ cells. Although NS protein was highly expressed in the nucleoli of all primordial germ cells, only a limited number of gonocytes showed NS expression in neonatal testes. In adult testes, NS protein was expressed at high levels in the nucleoli of spermatogonia and primary spermatocytes but at only low levels in round spermatids. To evaluate the properties of cells expressing high levels of NS, we generated transgenic reporter mice expressing green fluorescent protein (GFP) under the control of the NS promoter (NS-GFP Tg mice). In adult NS-GFP Tg testes, GFP and endogenous NS protein expression were correlated in spermatogonia and spermatocytes but GFP was also ectopically expressed in elongated spermatids and sperm. In testes of NS-GFP Tg embryos, neonates, and 10-day-old pups, however, GFP expression closely coincided with endogenous NS expression in developing germ cells. In contrast to a previous report, our results support the existence in neonatal testes of spermatogonial stem cells with long-term repopulating capacity. Furthermore, our data show that NS expression does not correlate with cell-cycle status during prepuberty, and that strong NS expression is essential for the maintenance of germline stem cell proliferation capacity. We conclude that NS is a marker of undifferentiated status in the germ cell lineage during prepubertal spermatogenesis.

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