The POU domain transcription factor POU3F1 is an important intrinsic regulator of GDNF-induced survival and self-renewal of mouse spermatogonial stem cells

Xin Wu; Jon M Oatley; Melissa J Oatley; Amy V Kaucher; Mary R Avarbock; Ralph L Brinster

doi:10.1095/biolreprod.109.083097

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The POU domain transcription factor POU3F1 is an important intrinsic regulator of GDNF-induced survival and self-renewal of mouse spermatogonial stem cells

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The POU domain transcription factor POU3F1 is an important intrinsic regulator of GDNF-induced survival and self-renewal of mouse spermatogonial stem cells

Xin Wu, Jon M Oatley, Melissa J Oatley, Amy V Kaucher, Mary R Avarbock and Ralph L Brinster

Biology of reproduction, Vol.82(6), pp.1103-1111

06/2010

DOI: https://doi.org/10.1095/biolreprod.109.083097

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https://hdl.handle.net/2376/103830

PMID: 20181621

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Abstract

Autocrine Communication

Testis - metabolism

Testis - cytology

Cell Survival

Spermatogenesis

Male

Nodal Protein - analysis

Stem Cells - metabolism

Spermatogonia - metabolism

Octamer Transcription Factor-6 - metabolism

Glial Cell Line-Derived Neurotrophic Factor - metabolism

Animals

Cell Division

Mice

Apoptosis

Continual spermatogenesis relies on a pool of spermatogonial stem cells (SSCs) that possess the capacity for self-renewal and differentiation. Maintenance of this pool depends on survival of SSCs throughout the lifetime of a male. Response to extrinsic stimulation from glial cell line-derived neurotrophic factor (GDNF), mediated by the PIK3/AKT signaling cascade, is a key pathway of SSC survival. In this study, we found that expression of the POU domain transcription factor POU3F1 in cultured SSCs is up-regulated via this mechanism. Reduction of Pou3f1 gene expression by short interfering RNA (siRNA) treatment induced apoptosis in cultured germ cell populations, and transplantation analyses revealed impaired SSC maintenance in vitro. POU3F1 expression was localized to spermatogonia in cross-sections of prepubertal and adult testes, implying a similar role in vivo. Through comparative analyses, we found that expression of POU5F1, another POU transcription factor implicated as essential for SSC self-renewal, is not regulated by GDNF in cultured SSCs. Transplantation analyses following siRNA treatment showed that POU5F1 expression is not essential for SSC maintenance in vitro. Additionally, expression of NODAL, a putative autocrine regulator of POU5F1 expression in mouse germ cells, could not be detected in SSCs isolated from testes or cultured SSCs. Collectively, these results indicate that POU3F1, but not POU5F1, is an intrinsic regulator of GDNF-induced survival and self-renewal of mouse SSCs.

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Title: The POU domain transcription factor POU3F1 is an important intrinsic regulator of GDNF-induced survival and self-renewal of mouse spermatogonial stem cells
Creators: Xin Wu - Department of Animal Biology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA, USA
Jon M Oatley
Melissa J Oatley
Amy V Kaucher
Mary R Avarbock
Ralph L Brinster
Publication Details: Biology of reproduction, Vol.82(6), pp.1103-1111
Academic Unit: Molecular Biosciences, School of
Publisher: United States
Grant note: R01 HD061665-02 / NICHD NIH HHS R21 HD058137-02 / NICHD NIH HHS HD052728 / NICHD NIH HHS R01 HD052728 / NICHD NIH HHS R01 HD061665 / NICHD NIH HHS R21 HD058137-01 / NICHD NIH HHS R21 HD058137 / NICHD NIH HHS R01 HD044445 / NICHD NIH HHS HD058137 / NICHD NIH HHS HD044445 / NICHD NIH HHS
Identifiers: 99900546932701842
Language: English
Resource Type: Journal article