Kang Hong Soon, Chen Liang-Yu, Lichti-Kaiser Kristin, Liao Grace, Gerrish Kevin, Bortner Carl D, Yao Humphrey H-C, Eddy Edward M, Jetten Anton M
Immunity, Inflammation and Disease Laboratory, National Institutes of Health, Research Triangle Park, North Carolina, USA.
Reproductive and Developmental Biology Laboratory, National Institutes of Health, Research Triangle Park, North Carolina, USA.
Stem Cells. 2016 Nov;34(11):2772-2783. doi: 10.1002/stem.2449. Epub 2016 Jul 11.
In this study, we identify a novel and essential role for the Krüppel-like zinc finger transcription factor GLI-similar 3 (GLIS3) in the regulation of postnatal spermatogenesis. We show that GLIS3 is expressed in gonocytes, spermatogonial stem cells (SSCs) and spermatogonial progenitors (SPCs), but not in differentiated spermatogonia and later stages of spermatogenesis or in somatic cells. Spermatogenesis is greatly impaired in GLIS3 knockout mice. Loss of GLIS3 function causes a moderate reduction in the number of gonocytes, but greatly affects the generation of SSCs/SPCs, and as a consequence the development of spermatocytes. Gene expression profiling demonstrated that the expression of genes associated with undifferentiated spermatogonia was dramatically decreased in GLIS3-deficient mice and that the cytoplasmic-to-nuclear translocation of FOXO1, which marks the gonocyte-to-SSC transition and is necessary for SSC self-renewal, is inhibited. These observations suggest that GLIS3 promotes the gonocyte-to-SSC transition and is a critical regulator of the dynamics of early postnatal spermatogenesis. Stem Cells 2016;34:2772-2783.
在本研究中，我们确定了Krüppel样锌指转录因子GLI-相似3（GLIS3）在出生后精子发生调控中的一种新的重要作用。我们发现GLIS3在生殖母细胞、精原干细胞（SSCs）和精原祖细胞（SPCs）中表达，但在分化的精原细胞、精子发生的后期阶段或体细胞中不表达。GLIS3基因敲除小鼠的精子发生严重受损。GLIS3功能缺失导致生殖母细胞数量适度减少，但极大地影响了SSCs/SPCs的产生，进而影响了精母细胞的发育。基因表达谱分析表明，在GLIS3缺陷小鼠中，与未分化精原细胞相关的基因表达显著降低，并且标记生殖母细胞向SSC转变且对SSC自我更新必不可少的FOXO1的细胞质到细胞核的转运受到抑制。这些观察结果表明，GLIS3促进生殖母细胞向SSC的转变，并且是出生后早期精子发生动态变化的关键调节因子。《干细胞》2016年；34卷：2772 - 2783页
