DNMT3L promotes quiescence in postnatal spermatogonial progenitor cells

Hung Fu Liao, Wendy S C Chen, Yu Hsiang Chen, Tzu Hao Kao, Yen Tzu Tseng, Chien Yueh Lee, Yu Chiao Chiu, Pei Lung Lee, Qian Jia Lin, Yung Hao Ching, Kenichiro Hata, Winston T K Cheng, Mong Hsun Tsai, Hiroyuki Sasaki, Hong Nerng Ho, Shinn Chih Wu, Yen-Hua Huang, Pauline Yen, Shau Ping Lin

研究成果: 雜誌貢獻文章

28 引文 斯高帕斯(Scopus)

摘要

The ability of adult stem cells to reside in a quiescent state is crucial for preventing premature exhaustion of the stem cell pool. However, the intrinsic epigenetic factors that regulate spermatogonial stem cell quiescence are largely unknown. Here, we investigate in mice how DNA methyltransferase 3-like (DNMT3L), an epigenetic regulator important for interpreting chromatin context and facilitating de novo DNA methylation, sustains the long-term male germ cell pool. We demonstrated that stem cell-enriched THY1+ spermatogonial stem/ progenitor cells (SPCs) constituted a DNMT3L-expressing population in postnatal testes. DNMT3L influenced the stability of promyelocytic leukemia zinc finger (PLZF), potentially by downregulating Cdk2/CDK2 expression, which sequestered CDK2-mediated PLZF degradation. Reduced PLZF in Dnmt3l KO THY1+ cells released its antagonist, Sallike protein 4A (SALL4A), which is associated with overactivated ERK and AKT signaling cascades. Furthermore, DNMT3L was required to suppressthe cell proliferation-promoting factor SALL4B in THY1+ SPCs and to prevent premature stem cell exhaustion. Our results indicate that DNMT3L is required to delicately balance the cycling and quiescence of SPCs. These findings reveal a novel role for DNMT3L in modulating postnatal SPC cell fate decisions.
原文英語
頁(從 - 到)2402-2413
頁數12
期刊Development
141
發行號12
DOIs
出版狀態已發佈 - 2014

ASJC Scopus subject areas

  • Developmental Biology
  • Molecular Biology

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    Liao, H. F., Chen, W. S. C., Chen, Y. H., Kao, T. H., Tseng, Y. T., Lee, C. Y., Chiu, Y. C., Lee, P. L., Lin, Q. J., Ching, Y. H., Hata, K., Cheng, W. T. K., Tsai, M. H., Sasaki, H., Ho, H. N., Wu, S. C., Huang, Y-H., Yen, P., & Lin, S. P. (2014). DNMT3L promotes quiescence in postnatal spermatogonial progenitor cells. Development, 141(12), 2402-2413. https://doi.org/10.1242/dev.105130