期刊
CELL STEM CELL
卷 11, 期 4, 页码 567-578出版社
CELL PRESS
DOI: 10.1016/j.stem.2012.06.011
关键词
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资金
- government of Japan
- Japan Science and Technology Agency (CREST)
- Mochida Memorial Foundation for Medical and Pharmaceutical Research
- Senri Life Science Foundation
- Ministry of Education, Culture, Sports, Science, and Technology (MEXT), Japan
- Grants-in-Aid for Scientific Research [23220011, 24111003, 24111001, 22390096, 23500507] Funding Source: KAKEN
Spermatogonial stem cells (SSCs) reside in specific niches within seminiferous tubules. These niches are thought to secrete chemotactic factors for SSCs, because SSCs migrate to them upon transplantation. However, the identity of these chemotactic molecules remains unknown. Here, we established a testis feeder cell culture system and used it to identify SSC chemotactic factors. When seeded on testis cells from infertile mice, SSCs migrated beneath the Sertoli cells and formed colonies with a cobblestone appearance that were very similar to those produced by hematopoietic stem cells. Cultured cells maintained SSC activity and fertility for at least 5 months. Cobblestone colony formation depended on GDNF and CXCL12, and dominant-negative GDNF receptor transfection or CXCL12 receptor deficiency reduced SSC colonization. Moreover, GDNF upregulated CXCL12 receptor expression, and CXCL12 transfection in Sertoli cells increased homing efficiency. Overall, our findings identify GDNF and CXCL12 as SSC chemotactic factors in vitro and in vivo.
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