Stem cell factor affects fate determination of human gonocytes in vitro.
The stem cell factor (SCF), binding its tyrosine kinase receptor c-Kit, has been shown to play essential roles in the proliferation, differentiation, and survival of germline cells. However, few reports are available about the effect of SCF on the development of human gonocytes within the fetal testis. The objective of this study was to investigate whether SCF affects the biological behaviors of human gonocytes before or after they enter the mitotic arrest stage. Employing an organ culture system, we observed that addition of exogenous SCF could influence the morphology of human gonocytes in vitro. Moreover, SCF was able to trigger the colony formation of round gonocytes, which were characterized positive for alkaline phosphatase activity, Oct-4, SSEA-4, and c-Kit as well. We found that SCF exerted actions in a dose- and age-dependent manner, although the stimulatory effect lasted no more than 14 days. We also showed that SCF played a role in suppressing the apoptosis of human gonocytes. Blocking of SCF signaling with either phosphatidylinositol 3-kinase or mitogen-activated protein kinase inhibitor resulted in similar apoptotic features as well as the SCF-withdrawal cultures. Taken together, we report that SCF acts as a potent regulator in the fate determination of human gonocytes. Our studies should form the basis for in vitro studies and facilitate investigation of the molecular mechanisms underlying this unique stage.
Tu
Jiongjiong
J
National Center of Human Stem Cell Research and Engineering, Central South University, Changsha, Hunan 410078, China.
Fan
Liqing
L
Tao
Ke
K
Zhu
Wenbing
W
Li
Jianjun
J
Lu
Guangxiu
G
D000469:Alkaline Phosphatase / Q000032:analysis; D017209:Apoptosis / Q000187:drug effects; D002454:Cell Differentiation / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D005455:Fluorescent Antibody Technique; D006028:Glycosphingolipids / Q000032:analysis; D006801:Humans; D008297:Male; D050814:Octamer Transcription Factor-3 / Q000032:analysis; D009924:Organ Culture Techniques; D019009:Proto-Oncogene Proteins c-kit / Q000032:analysis; D013090:Spermatocytes / Q000737:chemistry / Q000166:cytology* / Q000187:drug effects; D055746:Stage-Specific Embryonic Antigens; D019089:Stem Cell Factor / Q000494:pharmacology*; D013268:Stimulation, Chemical; D013737:Testis / Q000196:embryology*
D006028:Glycosphingolipids; D050814:Octamer Transcription Factor-3; D055746:Stage-Specific Embryonic Antigens; D019089:Stem Cell Factor; C066584:stage-specific embryonic antigen-4; D019009:Proto-Oncogene Proteins c-kit; D000469:Alkaline Phosphatase