Plzf is required in adult male germ cells for stem cell self-renewal
Plzf is required in adult male germ cells for stem cell self-renewal
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DOI：
10.1038/ng1366
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发表时间：
2004-06-01
期刊：
影响因子：
30.8
通讯作者：
Braun, RE
中科院分区：
文献类型：
--
作者：
Buaas, FW;Kirsh, AL;Braun, RE
成体生殖系干细胞具有自我更新、组织再生和产生大量分化后代的能力。我们在这里表明，经典的小鼠突变luxoid影响成人生殖干细胞自我更新。年轻的纯合子luxoid突变小鼠产生有限数量的正常精子，然后在出生后逐渐失去生殖系。移植研究表明，来自突变小鼠的生殖细胞不能在受体睾丸中定植，这表明这种缺陷是干细胞固有的。我们确定，luxoid突变体包含一个无义突变的基因编码Plzf，转录抑制因子，调节未分化细胞的表观遗传状态，并表明，Plzf与Oct4在未分化的精原细胞共表达。这是第一个在哺乳动物生殖细胞中进行干细胞自我更新所需的基因。
Adult germline stem cells are capable of self-renewal, tissue regeneration and production of large numbers of differentiated progeny. We show here that the classical mouse mutant luxoid affects adult germline stem cell self-renewal. Young homozygous luxoid mutant mice produce limited numbers of normal spermatozoa and then progressively lose their germ line after birth. Transplantation studies showed that germ cells from mutant mice did not colonize recipient testes, suggesting that the defect is intrinsic to the stem cells. We determined that the luxoid mutant contains a nonsense mutation in the gene encoding Plzf, a transcriptional repressor that regulates the epigenetic state of undifferentiated cells, and showed that Plzf is coexpressed with Oct4 in undifferentiated spermatogonia. This is the first gene shown to be required in germ cells for stem cell self-renewal in mammals.