Journal
EXPERIMENTAL CELL RESEARCH
Volume 317, Issue 10, Pages 1319-1329Publisher
ELSEVIER INC
DOI: 10.1016/j.yexcr.2011.03.013
Keywords
Tissue-specific stem cells; Germline; Self-renewal; Cell culture; Stem cell transplantation
Categories
Funding
- Canadian Institutes of Health Research [MOP-49444, 86532]
- Canada Foundation for Innovation [4177]
- RI-MUHC
- Stem Cell Network
- Fonds de la recherche en sante du Quebec
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Spermatogonial stem cells (SSCs) support life-long spermatogenesis by self-renewing and producing spermatogonia committed to differentiation. In vitro, SSCs form three-dimensional spermatogonial aggregates (clusters) when cultured with glial cell line-derived neurotrophic factor (GDNF) and fibroblast growth factor 2 (FGF2); serial passaging of clusters results in long-term SSC maintenance and expansion. However, the role of these growth factors in controlling patterns of SSC division and fate decision has not been understood thoroughly. We report here that in a short-term culture, GDNF and FGF2 increase the number of dividing SSCs, but not the total SSC number, compared to a no-growth-factor condition. Since the total germ cell number increases with growth factors, these results suggest that GDNF and FGF2 promote a SSC division pattern that sustains the size of the stem cell pool while generating committed progenitors. Our data also show that SSC numbers increase when the cluster structure is disintegrated and cell-cell interaction in clusters is disrupted. Collectively, these results suggest that in this culture system, GDNF and FGF2 stimulate SSC divisions that promote self-renewal and differentiation in the SSC population, and imply that the destruction of the cluster structure, a potential in vitro niche, may contribute to SSC expansion. (C) 2011 Elsevier Inc. All rights reserved.
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