Kontrollpunkte, welche die Stammzellfunktion und den Organerhalt in Antwort auf Telomerdysfunktion hemmen

响应端粒功能障碍而抑制干细胞功能和器官维持的检查点

• 批准号: 53203940
• 负责人: Professor Dr. Karl Lenhard Rudolph
• 金额: --
• 依托单位: Leibniz-Institut für Alternsforschung - Fritz-Lipmann-Institut e.V. (FLI)
• 依托单位国家: 德国
• 项目类别: Research Grants
• 财政年份: 2008
• 资助国家: 德国
• 起止时间: 2007-12-31 至 2015-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/53203940?language=en
• 关键词: Kontrollpunkte; welche; die; Stammzellfunktion; und

Telomere shortening limits proliferation of human cells to a finite number of cell division by inducing cell cycle arrest, senescence, or apoptosis in response to telomere dysfunction. These checkpoints can limit stem cell function, regeneration and organ homeostasis during ageing and chromic disease. In the proposed project we will analyse the functional influence of specific genes of the ATM/p53-cell cycle checkpoint (Exo1, 53bp1, Chk2) in restraining stem cell function, regeneration and organ homeostasis in response to telomere dysfunction and ageing in telomerase knockout mice. In addition, we will conduct an in vivo screen aiming to identify new genes limiting hematopoietic stem cell maintenance and function in response to telomere dysfunction.

端粒缩短通过响应端粒功能障碍诱导细胞周期停滞、衰老或凋亡，将人类细胞的增殖限制为有限数量的细胞分裂。这些检查点可以限制衰老和慢性疾病期间干细胞的功能、再生和器官稳态。在拟议的项目中，我们将分析 ATM/p53 细胞周期检查点的特定基因（Exo1、53bp1、Chk2）在抑制端粒酶敲除小鼠的端粒功能障碍和衰老过程中的干细胞功能、再生和器官稳态方面的功能影响。此外，我们将进行体内筛选，旨在识别限制造血干细胞维持和功能以应对端粒功能障碍的新基因。

项目成果

Senescence and apoptosis block hematopoietic activation of quiescent hematopoietic stem cells with short telomeres.

• DOI: 10.1182/blood-2014-04-568055
• 发表时间: 2014-11
• 期刊: Blood
• 影响因子: 20.3
• 作者: Jianwei Wang;Xin Lu;V. Sakk;C. Klein;K. Rudolph

Wip1 deficiency impairs haematopoietic stem cell function via p53 and mTORC1 pathways

• DOI: 10.1038/ncomms7808
• 发表时间: 2015-04-01
• 期刊: NATURE COMMUNICATIONS
• 影响因子: 16.6
• 作者: Chen, Zhiyang;Yi, Weiwei;Ju, Zhenyu
• 通讯作者: Ju, Zhenyu

A Differentiation Checkpoint Limits Hematopoietic Stem Cell Self-Renewal in Response to DNA Damage

• DOI: 10.1016/j.cell.2012.01.040
• 发表时间: 2012-03-02
• 期刊: CELL
• 影响因子: 64.5
• 作者: Wang, Jianwei;Sun, Qian;Rudolph, K. Lenhard
• 通讯作者: Rudolph, K. Lenhard

p21 promotes sustained liver regeneration and hepatocarcinogenesis in chronic cholestatic liver injury

• DOI: 10.1136/gutjnl-2013-304829
• 发表时间: 2014-09-01
• 期刊: GUT
• 影响因子: 24.5
• 作者: Marhenke, Silke;Buitrago-Molina, Laura Elisa;Vogel, Arndt
• 通讯作者: Vogel, Arndt

Telomere dysfunctional environment induces loss of quiescence and inherent impairments of hematopoietic stem cell function

端粒功能失调的环境会导致造血干细胞功能失去静止和固有损伤

• DOI: 10.1111/j.1474-9726.2012.00802.x
• 发表时间: 2012-06
• 期刊: Aging Cell
• 影响因子: 7.8
• 作者: Song Z;Zhang J;Ju Z;Rudolph KL
• 通讯作者: Rudolph KL