Identification of stem cells during prepubertal spermatogenesis via monitoring of nucleostemin promoter activity

Masako Ohmura, Kazuhito Naka, Takayuki Hoshii, Teruyuki Muraguchi, Haruhiko Shugo, Akira Tamase, Noriyuki Uema, Takako Ooshio, Fumio Arai, Keiyo Takubo, Go Nagamatsu, Isao Hamaguchi, Minoru Takagi, Masahiko Ishihara, Kazuhiro Sakurada, Hiromasa Miyaji, Toshio Suda, Atsushi Hirao

Research output: Contribution to journalArticle

26 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)3237-3246
Number of pages10
JournalStem Cells
Volume26
Issue number12
DOIs
Publication statusPublished - 2008 Dec

Fingerprint

Spermatogenesis
Green Fluorescent Proteins
Stem Cells
Testis
Germ Cells
Spermatogonia
Spermatocytes
Spermatids
Proteins
Cell Lineage
Nuclear Proteins
Tumor Cell Line
S Phase
Transgenic Mice
Spermatozoa
Cell Cycle
Embryonic Structures
Maintenance
Cell Proliferation
Genes

Keywords

  • Nucleostemin
  • Spermatogenesis
  • Stem cells
  • Transplantation

ASJC Scopus subject areas

  • Cell Biology
  • Developmental Biology
  • Molecular Medicine

Cite this

Ohmura, M., Naka, K., Hoshii, T., Muraguchi, T., Shugo, H., Tamase, A., ... Hirao, A. (2008). Identification of stem cells during prepubertal spermatogenesis via monitoring of nucleostemin promoter activity. Stem Cells, 26(12), 3237-3246. https://doi.org/10.1634/stemcells.2008-0506

Identification of stem cells during prepubertal spermatogenesis via monitoring of nucleostemin promoter activity. / Ohmura, Masako; Naka, Kazuhito; Hoshii, Takayuki; Muraguchi, Teruyuki; Shugo, Haruhiko; Tamase, Akira; Uema, Noriyuki; Ooshio, Takako; Arai, Fumio; Takubo, Keiyo; Nagamatsu, Go; Hamaguchi, Isao; Takagi, Minoru; Ishihara, Masahiko; Sakurada, Kazuhiro; Miyaji, Hiromasa; Suda, Toshio; Hirao, Atsushi.

In: Stem Cells, Vol. 26, No. 12, 12.2008, p. 3237-3246.

Research output: Contribution to journalArticle

Ohmura, M, Naka, K, Hoshii, T, Muraguchi, T, Shugo, H, Tamase, A, Uema, N, Ooshio, T, Arai, F, Takubo, K, Nagamatsu, G, Hamaguchi, I, Takagi, M, Ishihara, M, Sakurada, K, Miyaji, H, Suda, T & Hirao, A 2008, 'Identification of stem cells during prepubertal spermatogenesis via monitoring of nucleostemin promoter activity', Stem Cells, vol. 26, no. 12, pp. 3237-3246. https://doi.org/10.1634/stemcells.2008-0506
Ohmura, Masako ; Naka, Kazuhito ; Hoshii, Takayuki ; Muraguchi, Teruyuki ; Shugo, Haruhiko ; Tamase, Akira ; Uema, Noriyuki ; Ooshio, Takako ; Arai, Fumio ; Takubo, Keiyo ; Nagamatsu, Go ; Hamaguchi, Isao ; Takagi, Minoru ; Ishihara, Masahiko ; Sakurada, Kazuhiro ; Miyaji, Hiromasa ; Suda, Toshio ; Hirao, Atsushi. / Identification of stem cells during prepubertal spermatogenesis via monitoring of nucleostemin promoter activity. In: Stem Cells. 2008 ; Vol. 26, No. 12. pp. 3237-3246.
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