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

    Research output: Contribution to journalArticle

    29 Citations (Scopus)

    Abstract

    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.

    Original languageEnglish
    Pages (from-to)2402-2413
    Number of pages12
    JournalDevelopment (Cambridge)
    Volume141
    Issue number12
    DOIs
    Publication statusPublished - Jan 1 2014

    All Science Journal Classification (ASJC) codes

    • Molecular Biology
    • Developmental Biology

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  • Cite this

    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 (Cambridge), 141(12), 2402-2413. https://doi.org/10.1242/dev.105130