Stochastic Telomere Shortening and the Route to Limitless Replicative Potential

Journal of computational biology: A journal of computational molecular cell biology

ZhuoqinYang^1¹  YusongYe^1²  JinzhiLei^2,3³ 

[1] Address correspondence to: Dr. Jinzhi Lei, Zhou Pei-Yuan Center for Applied Mathematics, MOE Key Laboratory of Bioinformatics, Tsinghua University, Beijing 100084, China^2;School of Mathematics and Systems Science and LMIB, Beihang University, Beijing, China^1;Zhou Pei-Yuan Center for Applied Mathematics, MOE Key Laboratory of Bioinformatics, Tsinghua University, Beijing, China^3

关键词: cell immortalization;    telomerase;    telomere;    tumorigenesis.;   

DOI  :  10.1089/cmb.2018.0234

学科分类：生物科学（综合）

来源: Mary Ann Liebert, Inc. Publishers

【 摘 要 】

In human tissues, the replicative potential of stem cells is limited by the shortening of telomere, limitless replicative potential is a hallmark of cancer. Telomere length changes stochastically during cell division mainly due to the competition between the end replication problem and telomerase, short telomere can lead to replicative senescence and cell apoptosis. Here, we investigate how stochastic changes of telomere length in individual cells may affect the population dynamics of clonal growth. We established a computational model that couples telomerase-regulated stochastic telomere length changes with the replicative potential of clones. Model simulations reveal qualitative dependence of clone proliferation potential with activities of telomerase; mutations in cells to alter the activities of telomerase and its inhibitors can induce abnormal tissue growth and lead to limitless replicative potential.

【 授权许可】

Unknown