Essential role of Plzf in maintenance of spermatogonial stem cells
Essential role of Plzf in maintenance of spermatogonial stem cells
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DOI：
10.1038/ng1367
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发表时间：
2004-06-01
期刊：
影响因子：
30.8
通讯作者：
Pandolfi, PP
中科院分区：
文献类型：
--
作者：
Costoya, JA;Hobbs, RM;Pandolfi, PP
精原细胞是睾丸的有丝分裂生殖细胞，其自我更新并分化为精子的分子机制尚不清楚（1,2）。我们发现编码转录抑制因子Plzf的Zfp145在精子发生中起着至关重要的作用。Zfp145的表达仅限于性腺细胞和未分化的精原细胞，而在缺乏这些细胞的W/W-v突变体的小管中不表达。缺乏Zfp145的小鼠随着年龄的增长精子原细胞逐渐丧失，与细胞凋亡增加和随后的小管结构丧失有关，但没有明显的分化缺陷或支持的Sertoli细胞的丧失。精原细胞移植实验揭示了成人精原干细胞的耗竭。对睾丸变性前zfp145缺失小鼠的精原细胞进行微阵列分析，发现与精子发生相关的基因表达谱发生改变。这些结果确定Plzf是睾丸中精原细胞特异性转录因子，需要调节干细胞库的自我更新和维持。
Little is known of the molecular mechanisms whereby spermatogonia, mitotic germ cells of the testis, self-renew and differentiate into sperm(1,2). Here we show that Zfp145, encoding the transcriptional repressor Plzf, has a crucial role in spermatogenesis. Zfp145 expression was restricted to gonocytes and undifferentiated spermatogonia and was absent in tubules of W/W-v mutants that lack these cells. Mice lacking Zfp145 underwent a progressive loss of spermatogonia with age, associated with increases in apoptosis and subsequent loss of tubule structure but without overt differentiation defects or loss of the supporting Sertoli cells. Spermatogonial transplantation experiments revealed a depletion of spermatogonial stem cells in the adult. Microarray analysis of isolated spermatogonia from Zfp145-null mice before testis degeneration showed alterations in the expression profile of genes associated with spermatogenesis. These results identify Plzf as a spermatogonia-specific transcription factor in the testis that is required to regulate self-renewal and maintenance of the stem cell pool.