The CDKN1B-RB1-E2F1 pathway protects mouse spermatogonial stem cells from genomic damage

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抄録

Spermatogonial stem cells (SSCs) undergo self-renewal divisions to provide the foundation for spermatogenesis. Although <i>Rb1</i> deficiency is reportedly essential for SSC self-renewal, its mechanism has remained unknown. Here we report that <i>Rb1</i> is critical for cell cycle progression and protection of SSCs from DNA double-strand breaks (DSBs). Cultured SSCs depleted of <i>Cdkn1b</i> proliferated poorly and showed diminished expression of CDK4 and RB1, thereby leading to hypophosphorylation of RB1. <i>Rb1</i> deficiency induced cell cycle arrest and apoptosis in cultured SSCs, which expressed markers for DNA DSBs. This DNA damage is caused by increased E2F1 activity, the depletion of which decreased DNA DSBs caused by <i>Rb1</i> deficiency. Depletion of <i>Cdkn1a</i> and <i>Bbc3</i>, which were upregulated by <i>Trp53</i>, rescued <i>Rb1</i>-deficient cells from undergoing cell cycle arrest and apoptosis. These results suggest that the CDKN1B-RB1-E2F1 pathway is essential for SSC self-renewal and protects SSCs against genomic damage.

収録刊行物

  • 家畜繁殖研究會誌

    家畜繁殖研究會誌 61(4), 305-316, 2015

    日本繁殖生物学会

各種コード

  • NII論文ID(NAID)
    130005094647
  • NII書誌ID(NCID)
    AA10936678
  • 本文言語コード
    ENG
  • 資料種別
    journal article
  • ISSN
    0916-8818
  • NDL 記事登録ID
    026728108
  • NDL 請求記号
    Z54-H305
  • データ提供元
    NDL  IR  J-STAGE 
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