Departments of Pathology & Immunology, Baylor College of Medicine, Houston, Texas, United States of America.
PLoS One. 2013 Aug 15;8(8):e72689. doi: 10.1371/journal.pone.0072689. eCollection 2013.
The spermatogonial stem cell (SSC) compartment is maintained by self-renewal of stem cells as well as fragmentation of differentiating spermatogonia through abscission of intercellular bridges in a random and stochastic manner. The molecular mechanisms that regulate this reversible developmental lineage remain to be elucidated. Here, we show that histone H3K27 demethylase, JMJD3 (KDM6B), regulates the fragmentation of spermatogonial cysts. Down-regulation of Jmjd3 in SSCs promotes an increase in undifferentiated spermatogonia but does not affect their differentiation. Germ cell-specific Jmjd3 null male mice have larger testes and sire offspring for a longer period compared to controls, likely secondary to increased and prolonged maintenance of the spermatogonial compartment. Moreover, JMJD3 deficiency induces frequent fragmentation of spermatogonial cysts by abscission of intercellular bridges. These results suggest that JMJD3 controls the spermatogonial compartment through the regulation of fragmentation of spermatogonial cysts and this mechanism may be involved in maintenance of diverse stem cell niches.
精原干细胞 (SSC) 区室通过干细胞的自我更新以及通过细胞间桥的断裂以随机和随机的方式使分化精原细胞分裂来维持。调节这种可逆发育谱系的分子机制仍有待阐明。在这里，我们表明组蛋白 H3K27 去甲基酶 JMJD3（KDM6B）调节精原细胞囊泡的断裂。SSC 中 Jmjd3 的下调促进未分化精原细胞的增加，但不影响它们的分化。与对照相比，生殖细胞特异性 Jmjd3 缺失的雄性小鼠具有更大的睾丸并且能够更长时间地生育后代，这可能是由于精原细胞区室的增加和延长维持所致。此外，JMJD3 缺乏通过细胞间桥的断裂诱导精原细胞囊泡的频繁断裂。这些结果表明，JMJD3 通过调节精原细胞囊泡的断裂来控制精原细胞区室，并且该机制可能参与维持多种干细胞龛。
