Journal
BIOLOGY OF REPRODUCTION
Volume 82, Issue 6, Pages 1103-1111Publisher
OXFORD UNIV PRESS INC
DOI: 10.1095/biolreprod.109.083097
Keywords
GDNF; POU3F1; POU5F1; self-renewal; spermatogonial stem cell
Categories
Funding
- Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health [HD044445, HD052728, HD058137]
- Robert J. Kleberg, Jr. and Helen C. Kleberg Foundation
- The Pennsylvania State University
- EUNICE KENNEDY SHRIVER NATIONAL INSTITUTE OF CHILD HEALTH & HUMAN DEVELOPMENT [R01HD061665] Funding Source: NIH RePORTER
- EUNICE KENNEDY SHRIVER NATIONAL INSTITUTE OF CHILD HEALTH &HUMAN DEVELOPMENT [R01HD044445, R01HD052728, R21HD058137] Funding Source: NIH RePORTER
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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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