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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24 February 2010
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
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Biology of Reproduction
Vol. 82 • No. 6
June 2010
Vol. 82 • No. 6
June 2010
GDNF
POU3F1
POU5F1
Self-renewal
spermatogonial stem cell