Transmission distortion by loss of p21 or p27 cyclin-dependent kinase inhibitors following competitive spermatogonial transplantation

摘要: Spermatogonial stem cells (SSCs) undergo self-renewal division to support spermatogenesis. Although several positive regulators of SSC have been identified, little is known about the mechanisms that negatively regulate SSCs. Here we developed a novel transplantation assay for SSCs and demonstrate p21 p27 cyclin-dependent kinase inhibitors play critical roles in differentiation. Overexpression or abrogated proliferation cultured vitro, their expression levels were downregulated by exogenous signals. In contrast, no apparent defects found p27-deficient spermatogonial transplantation. However, competitive with WT revealed loss either gene causes distortion germline transmission: p21-deficiency facilitated mutant offspring production, whereas transmission was limited p27-deficiency. Serial also showed p27, but not p21, decreases secondary colony formation, suggesting appropriate amounts are necessary sustaining self-renewal. Thus, regulating balance between differentiation, technique will be useful analyzing subtle spermatogenesis evident traditional