期刊
PLOS ONE
卷 13, 期 4, 页码 -出版社
PUBLIC LIBRARY SCIENCE
DOI: 10.1371/journal.pone.0195747
关键词
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资金
- National Institutes of Health [R01CA112226]
- Cancer Center Support Grant at the Laura and Isaac Perlmutter Cancer Center [NIH/NCI P30CA016087]
- NYSTEM [C026719]
Male mammals must simultaneously produce prodigious numbers of sperm and maintain an adequate reserve of stem cells to ensure continuous production of gametes throughout life. Failures in the mechanisms responsible for balancing germ cell differentiation and spermatogonial stem cell (SSC) self-renewal can result in infertility. We discovered a novel requirement for Ubiquitous Expressed Transcript (UXT) in spermatogenesis by developing the first knockout mouse model for this gene. Constitutive deletion of Uxt is embryonic lethal, while conditional knockout in the male germline results in a Sertoli cell-only phenotype during the first wave of spermatogenesis that does not recover in the adult. This phenotype begins to manifest between 6 and 7 days post-partum, just before meiotic entry. Gene expression analysis revealed that Uxt deletion downregulates the transcription of genes governing SSC self-renewal, differentiation, and meiosis, consistent with its previously defined role as a transcriptional co-factor. Our study has revealed the first in vivo function for UXT in the mammalian germline as a regulator of distinct transcriptional programs in SSCs and differentiating spermatogonia.
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