GDNF Family Receptor alpha1 Phenotype of Spermatogonial Stem Cells in Immature Mouse Testes
Spermatogonial stem cells (SSCs) are essential for spermatogenesis, and these adult tissue stem cells balance self-renewal and differentiation to meet the biological demand of the testis. The developmental dynamics of SSCs are controlled, in part, by factors in the stem cell niche, which is located...
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Veröffentlicht in: | Biology of reproduction 2005-11, Vol.73 (5), p.1011-1016 |
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Zusammenfassung: | Spermatogonial stem cells (SSCs) are essential for spermatogenesis, and these adult tissue stem cells balance self-renewal
and differentiation to meet the biological demand of the testis. The developmental dynamics of SSCs are controlled, in part,
by factors in the stem cell niche, which is located on the basement membrane of seminiferous tubules situated among Sertoli
cells. Sertoli cells produce glial cell line-derived neurotrophic factor (GDNF), and disruption of GDNF expression results
in spermatogenic defects and infertility. The GDNF signals through a receptor complex that includes GDNF family receptor α1
(GFRA1), which is thought to be expressed by SSCs. However, expression of GFRA1 on SSCs has not been confirmed by in vivo
functional assay, which is the only method that allows definitive identification of SSCs. Therefore, we fractionated mouse
pup testis cells based on GFRA1 expression using magnetic activated cell sorting. The sorted and depleted fractions of GFRA1
were characterized for germ cell markers by immunocytochemistry and for stem cell activity by germ cell transplantation. The
GFRA1-positive cell fraction coeluted with other markers of SSCs, including ITGA6 and CD9, and was significantly depleted
of KIT-positive cells. The transplantation results confirmed that a subpopulation of SSCs expresses GFRA1, but also that the
stem cell pool is heterogeneous with respect to the level of GFRA1 expression. Interestingly, POU5F1-positive cells were enriched
nearly 15-fold in the GFRA1-selected fraction, possibly suggesting heterogeneity of developmental potential within the stem
cell pool.
Abstract
Spermatogonial stem cells can be enriched using magnetic activated cell sorting with GFRA1 antibodies, revealing a distinct
GFRA1-positive subpopulation in the mouse pup testis that coexpresses the pluripotency marker POU5F1 |
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ISSN: | 0006-3363 1529-7268 |
DOI: | 10.1095/biolreprod.105.043810 |