Understanding telomere privilege in pluripotent stem cells

了解多能干细胞的端粒特权

• 批准号: DP210103885
• 负责人: Prof Anthony Cesare
• 金额: $ 39.1万
• 依托单位: The University of Sydney
• 依托单位国家: 澳大利亚
• 项目类别: Discovery Projects
• 财政年份: 2021
• 资助国家: 澳大利亚
• 起止时间: 2021-01-01 至 2023-12-31
• 项目状态: 已结题
• 来源: https://dataportal.arc.gov.au/RGS/Web/Grants/DP210103885
• 关键词: Understanding; telomere; privilege; pluripotent; stem

We recently identified that fundamental mechanisms which protect chromosome ends (i.e. “telomeres”) are not conserved between somatic and embryo-derived stem cells. This discovery is without precedent and challenges the dogmatic expectation that cellular functions promoting genome stability are conserved in stem cells. We term the unexpected protective capacity of pluripotent chromosome ends “telomere privilege”. Here we will uncover the molecular, genomic, and proteomic regulators or telomere privilege; determine the breath of telomere privilege in stem cell lineages; elucidate the functional significance of telomere privilege; and exploit telomere privilege to study fundamental biology related to telomeres and the DNA damage response.

我们最近发现，保护染色体末端（即“端粒”）的基本机制在体细胞和胚胎干细胞之间并不保守。这一发现是前所未有的，并挑战了促进基因组稳定性的细胞功能在干细胞中是保守的教条期望。我们将多能染色体末端的意外保护能力称为“端粒特权”。在这里，我们将揭示分子，基因组和蛋白质组调节或端粒特权;确定端粒特权在干细胞谱系中的呼吸;阐明端粒特权的功能意义;并利用端粒特权研究与端粒和DNA损伤反应相关的基础生物学。