Distinct characteristics of two types of alternative lengthening of telomeres in mouse embryonic stem cells

• Published in: Nucleic Acids Research Vol. 51; no. 17; pp. 9122 - 9143
• Main Authors: Sung, Sanghyun, Kim, Eunkyeong, Niida, Hiroyuki, Kim, Chuna, Lee, Junho
• Format: Journal Article
• Language: English
• Published: England Oxford University Press (OUP) 22.09.2023; Oxford University Press
• Subjects: Animals; Genome Integrity, Repair and; Genome Integrity, Repair and Replication; Mice; Mouse Embryonic Stem Cells; Mutation; Telomerase; Telomere; Telomere Homeostasis
• ISSN: 0305-1048; 1362-4962; 1362-4962
• DOI: 10.1093/nar/gkad617

Abstract Telomere length must be maintained in actively dividing cells to avoid cellular arrest or death. In the absence of telomerase activity, activation of alternative lengthening of telomeres (ALT) allows the maintenance of telomeric length and prolongs the cellular lifespan. Our previous studies have established two types of ALT survivors from mouse embryonic stem cells. The key differences between these ALT survivors are telomere-constituting sequences: non-telomeric sequences and canonical telomeric repeats, with each type of ALT survivors being referred to as type I and type II, respectively. We explored how the characteristics of the two types of ALT lines reflect their fates using multi-omics approaches. The most notable gene expression signatures of type I and type II ALT cell lines were chromatin remodelling and DNA repair, respectively. Compared with type II cells, type I ALT cells accumulated more mutations and demonstrated persistent telomere instability. These findings indicate that cells of the same origin have separate routes for survival, thus providing insights into the plasticity of crisis-suffering cells and cancers. Graphical Abstract Graphical Abstract