Cellular Senescence: Ex Vivo p53-Dependent Asymmetric Cell Kinetics.
Cellular Senescence: Ex Vivo p53-Dependent Asymmetric Cell Kinetics.
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DOI：
10.1155/s1110724301000079
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发表时间：
2001
影响因子：
--
通讯作者：
Sherley JL
中科院分区：
文献类型：
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作者：
Rambhatla L;Bohn SA;Stadler PB;Boyd JT;Coss RA;Sherley JL
尽管衰老是整倍体哺乳动物细胞的一个决定性特性，但其生理基础仍然不清楚。此前，衰老模型中尚未考虑正常组织细胞的细胞动力学特性。我们现在提供的证据表明，衰老实际上是正常体内成体干细胞动力学在培养物中延伸的自然结果。这一衰老概念基于我们的发现，即经过工程改造的细胞有条件地表达公认的肿瘤抑制蛋白和衰老因子 p53，表现出不对称的细胞动力学。在体内，不对称细胞动力学对于成体干细胞的维持至关重要；在体外，相同的细胞动力学产生衰老作为简单的动力学终点。这种新的衰老“不对称细胞动力学模型”提出了在培养物中分离和繁殖体组织干细胞的新策略。
Although senescence is a defining property of euploid mammalian cells, its physiologic basis remains obscure. Previously, cell kinetics properties of normal tissue cells have not been considered in models for senescence. We now provide evidence that senescence is in fact the natural consequence of normal in vivo somatic stem cell kinetics extended in culture. This concept of senescence is based on our discovery that cells engineered to conditionally express the well-recognized tumor suppressor protein and senescence factor, p53, exhibit asymmetric cell kinetics. In vivo, asymmetric cell kinetics are essential for maintenance of somatic stem cells; ex vivo, the same cell kinetics yield senescence as a simple kinetic endpoint. This new “asymmetric cell kinetics model” for senescence suggests novel strategies for the isolation and propagation of somatic tissue stem cells in culture.