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PMID: 20505165 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Regulation of mouse spermatogonial stem cell differentiation by STAT3 signaling.

Biology of reproduction ·Vol. 83 ·No. 3 ·2010-09-00 ·Pages 427-33

Oatley JM, Kaucher AV, Avarbock MR, Brinster RL

Abstract

Homeostasis of many tissues is maintained by self-renewal and differentiation of stem cells. Spermatogenesis is one such system relying on the activity of spermatogonial stem cells (SSCs). Several key regulators of SSC self-renewal have been identified, yet knowledge of molecules that control SSC differentiation is undefined. In this study, we found that transient impairment of STAT3 signaling enhances SSC self-renewal in vitro without affecting general spermatogonial proliferation, indicating an alteration in the balance of SSC fate decisions that inhibited differentiation. Confirming this observation, short hairpin RNA-mediated stable reduction of STAT3 expression in cultured SSCs abolished their ability to differentiate beyond the undifferentiated spermatogonial stage following transplantation into recipient testes. Collectively, these results demonstrate that STAT3 promotes the differentiation of SSCs. In contrast, STAT3 plays a central role in maintaining self-renewal of mouse embryonic stem cells, and STAT signaling is essential for self-renewal of male germline stem cells in Drosophila.

MeSH Terms
Analysis of Variance Animals Blotting, Western Cell Proliferation Cells, Cultured Flow Cytometry Immunohistochemistry Male Mice Phosphorylation/physiology RNA, Small Interfering Reverse Transcriptase Polymerase Chain Reaction STAT3 Transcription Factor/metabolism Signal Transduction/physiology Spermatogenesis/physiology Spermatogonia/metabolism,transplantation Transfection
Chemicals
RNA, Small Interfering STAT3 Transcription Factor
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Oatley Jon M
Center for Reproductive Biology and Health, Department of Dairy and Animal Science, The Pennsylvania State University, University Park, Pennsylvania 16802, USA. [email protected]
Kaucher Amy V
Avarbock Mary R
Brinster Ralph L
References (33)
33 references, click to expand
  1. Akt mediates self-renewal division of mouse spermatogonial stem cells.
    Development. 2007 May;134(10):1853-9 PMID: 17428826
  2. Neurogenin3 delineates the earliest stages of spermatogenesis in the mouse testis.
    Dev Biol. 2004 May 15;269(2):447-58 PMID: 15110712
  3. Role of c-kit in mouse spermatogenesis: identification of spermatogonia as a specific site of c-kit expression and function.
    Development. 1991 Oct;113(2):689-99 PMID: 1723681
  4. Gonadal expression of c-kit encoded at the W locus of the mouse.
    Development. 1990 Dec;110(4):1057-69 PMID: 1712701
  5. Capacity for stochastic self-renewal and differentiation in mammalian spermatogonial stem cells.
    J Cell Biol. 2009 Nov 16;187(4):513-24 PMID: 19948499
  6. Self-renewal of pluripotent embryonic stem cells is mediated via activation of STAT3.
    Genes Dev. 1998 Jul 1;12(13):2048-60 PMID: 9649508
  7. Growth factors essential for self-renewal and expansion of mouse spermatogonial stem cells.
    Proc Natl Acad Sci U S A. 2004 Nov 23;101(47):16489-94 PMID: 15520394
  8. Regulation of spermatogonial stem cell self-renewal in mammals.
    Annu Rev Cell Dev Biol. 2008;24:263-86 PMID: 18588486
  9. Genetic reconstruction of mouse spermatogonial stem cell self-renewal in vitro by Ras-cyclin D2 activation.
    Cell Stem Cell. 2009 Jul 2;5(1):76-86 PMID: 19570516
  10. Essential role of STAT3 for embryonic stem cell pluripotency.
    Proc Natl Acad Sci U S A. 1999 Mar 16;96(6):2846-51 PMID: 10077599
  11. Stem cell self-renewal specified by JAK-STAT activation in response to a support cell cue.
    Science. 2001 Dec 21;294(5551):2542-5 PMID: 11752574
  12. Clonal origin of germ cell colonies after spermatogonial transplantation in mice.
    Biol Reprod. 2006 Jul;75(1):68-74 PMID: 16598026
  13. Control of stem cell self-renewal in Drosophila spermatogenesis by JAK-STAT signaling.
    Science. 2001 Dec 21;294(5551):2546-9 PMID: 11752575
  14. Phenotypic plasticity of mouse spermatogonial stem cells.
    PLoS One. 2009 Nov 19;4(11):e7909 PMID: 19936070
  15. The spermatogonial stem cell population in adult rats. I. Their morphology, proliferation and maturation.
    Anat Rec. 1971 Mar;169(3):533-57 PMID: 5550532
  16. Targeted disruption of the mouse Stat3 gene leads to early embryonic lethality.
    Proc Natl Acad Sci U S A. 1997 Apr 15;94(8):3801-4 PMID: 9108058
  17. THY1 is a conserved marker of undifferentiated spermatogonia in the pre-pubertal bull testis.
    Reproduction. 2010 May;139(5):893-903 PMID: 20154176
  18. Genetic and epigenetic properties of mouse male germline stem cells during long-term culture.
    Development. 2005 Sep;132(18):4155-63 PMID: 16107472
  19. Identifying genes important for spermatogonial stem cell self-renewal and survival.
    Proc Natl Acad Sci U S A. 2006 Jun 20;103(25):9524-9 PMID: 16740658
  20. Essential role of Plzf in maintenance of spermatogonial stem cells.
    Nat Genet. 2004 Jun;36(6):653-9 PMID: 15156143
  21. Germline transmission of donor haplotype following spermatogonial transplantation.
    Proc Natl Acad Sci U S A. 1994 Nov 22;91(24):11303-7 PMID: 7972054
  22. Spermatogenesis following male germ-cell transplantation.
    Proc Natl Acad Sci U S A. 1994 Nov 22;91(24):11298-302 PMID: 7972053
  23. Expression of Stat3 in germ cells of developing and adult mouse ovaries and testes.
    Gene Expr Patterns. 2005 Apr;5(4):475-82 PMID: 15749075
  24. Spermatogonial stem cells share some, but not all, phenotypic and functional characteristics with other stem cells.
    Proc Natl Acad Sci U S A. 2003 May 27;100(11):6487-92 PMID: 12738887
  25. Differential expression of c-kit in mouse undifferentiated and differentiating type A spermatogonia.
    Endocrinology. 1999 Dec;140(12):5894-900 PMID: 10579355
  26. Plzf is required in adult male germ cells for stem cell self-renewal.
    Nat Genet. 2004 Jun;36(6):647-52 PMID: 15156142
  27. All you wanted to know about spermatogonia but were afraid to ask.
    J Androl. 2000 Nov-Dec;21(6):776-98 PMID: 11105904
  28. Molecular dissection of the male germ cell lineage identifies putative spermatogonial stem cells in rhesus macaques.
    Hum Reprod. 2009 Jul;24(7):1704-16 PMID: 19336441
  29. Spermatogonial stem-cell renewal in the mouse.
    Anat Rec. 1971 Mar;169(3):515-31 PMID: 5550531
  30. Glial cell line-derived neurotrophic factor regulation of genes essential for self-renewal of mouse spermatogonial stem cells is dependent on Src family kinase signaling.
    J Biol Chem. 2007 Aug 31;282(35):25842-51 PMID: 17597063
  31. The RNA-binding protein NANOS2 is required to maintain murine spermatogonial stem cells.
    Science. 2009 Sep 11;325(5946):1394-8 PMID: 19745153
  32. Regeneration of male germline stem cells by spermatogonial dedifferentiation in vivo.
    Science. 2004 May 28;304(5675):1331-4 PMID: 15143218
  33. Spermatogonial stem cells.
    Methods Enzymol. 2006;419:259-82 PMID: 17141059
Article Info
Journal
Biology of reproduction
Abbr.
Biol Reprod
ISSN
1529-7268
DOI
10.1095/biolreprod.109.083352
Email
[email protected]
Published
2010-09-00
Epub
2010-00-26
Pages
427-33
Language
English
Region
United States
NLM ID
0207224
PMCID
PMC2924805
Subset
IM
Grants
NICHD NIH HHS · R01 HD052728 · United States
NICHD NIH HHS · HD058137 · United States
NICHD NIH HHS · HD052728 · United States
NICHD NIH HHS · R01 HD061665-02 · United States
NICHD NIH HHS · R01 HD061665 · United States
NIGMS NIH HHS · R01 GM036745 · United States
NICHD NIH HHS · R01 HD044445 · United States
NICHD NIH HHS · R21 HD058137 · United States
NICHD NIH HHS · R21 HD058137-02 · United States
NICHD NIH HHS · R21 HD058137-01 · United States
NICHD NIH HHS · HD044445 · United States
External Links
PubMed source DOI: 10.1095/biolreprod.109.083352 PMC Full Text View journal details
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