SPOC1 (PHF13) is required for spermatogonial stem cell differentiation and sustained spermatogenesis
SPOC1 (PHF13) is required for spermatogonial stem cell differentiation and sustained spermatogenesis
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DOI：
10.1242/jcs.085936
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发表时间：
2011-09-15
影响因子：
4
通讯作者：
Winterpacht, Andreas
中科院分区：
文献类型：
--
作者：
Boerdlein, Annegret;Scherthan, Harry;Winterpacht, Andreas
SPOC1 (PHF13) 是最近发现的一种蛋白质，已被证明与体细胞染色质动态关联，调节染色质压缩并对正确的细胞分裂很重要。在这里，我们报告了 SPOC1 在早幼粒细胞白血病锌指 (PLZF) 阳性的小鼠睾丸未分化精原干细胞 (SSC) 中的表达。为了进一步研究 SPOC1 在生殖细胞中的生物学功能，我们从基因捕获胚胎干细胞克隆中产生了 Spoc1 突变小鼠。青春期后纯合的 Spoc1(-/-) 动物表现出睾丸小管最初正常生殖上皮的生殖细胞明显进行性丧失，导致睾丸发育不全。这种损失首先影响生殖细胞的非 SSC 阶段，然后在稍后的时间点影响未分化的精原细胞。值得注意的是，在年轻小鼠（> 10周龄）中，在所有生殖细胞（> 20周龄）连续丧失之前，未分化的A（对齐）（A（al））精原细胞数量短暂增加。原代 Spoc1(-/-) 生殖细胞的数量、生殖细胞的增殖以及减数分裂的开始和进展均正常，但我们注意到 Spoc1(-/-) 睾丸中的细胞凋亡水平显着升高。综上所述，数据表明 SPOC1 对于睾丸干细胞分化和持续精子发生是不可或缺的。
SPOC1 (PHF13) is a recently identified protein that has been shown to dynamically associate with somatic chromatin, to modulate chromatin compaction and to be important for proper cell division. Here, we report on the expression of SPOC1 in promyelocytic leukaemia zinc finger (PLZF)-positive undifferentiated spermatogonial stem cells (SSCs) of the mouse testis. To investigate further the biological function of SPOC1 in germ cells we generated Spoc1 mutant mice from a gene-trap embryonic stem cell clone. Postpubertal homozygous Spoc1(-/-) animals displayed a pronounced progressive loss of germ cells from an initially normal germ epithelium of the testis tubules leading to testis hypoplasia. This loss first affected non-SSC stages of germ cells and then, at a later time point, the undifferentiated spermatogonia. Remarkably, successive loss of all germ cells (at > 20 weeks of age) was preceded by a transient increase in the number of undifferentiated A(aligned) (A(al)) spermatogonia in younger mice (at > 10 weeks of age). The number of primary Spoc1(-/-) gonocytes, the proliferation of germ cells, and the initiation and progression of meiosis was normal, but we noted a significantly elevated level of apoptosis in the Spoc1(-/-) testis. Taken together, the data argue that SPOC1 is indispensable for stem cell differentiation in the testis and for sustained spermatogenesis.