Self-Renewal Signalling in Presenescent Tetraploid IMR90 CellsReport as inadecuate

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Journal of Aging ResearchVolume 2011 2011, Article ID 103253, 14 pages

Research Article

Latvian Biomedical Research and Study Centre, Ratsupites 1, 1067 Riga, Latvia

Latvian Institute of Organic Synthesis, Aizkraukles 21, 1006 Riga, Latvia

Received 15 December 2010; Revised 22 February 2011; Accepted 25 February 2011

Academic Editor: Noam Shomron

Copyright © 2011 Anda Huna et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


Endopolyploidy and genomic instability are shared features of both stress-induced cellular senescence and malignant growth. Here, we examined these facets in the widely used normal human fibroblast model of senescence, IMR90. At the presenescence stage, a small 2–7% proportion of cells overcome the 4n-G1 checkpoint, simultaneously inducing self-renewal NANOG-positivity, the DNA damage response DDR; γ-H2AX-positive foci, and senescence p16inka4a- and p21CIP1-positivity signalling, some cells reach octoploid DNA content and divide. All of these markers initially appear and partially colocalise in the perinucleolar compartment. Further, with development of senescence and accumulation of p16inka4a and p21CIP1, NANOG is downregulated in most cells. The cells increasingly arrest in the 4n-G1 fraction, completely halt divisions and ultimately degenerate. A positive link between DDR, self-renewal, and senescence signalling is initiated in the cells overcoming the tetraploidy barrier, indicating that cellular and molecular context of induced tetraploidy during this period of presenescence is favourable for carcinogenesis.

Author: Anda Huna, Kristine Salmina, Elina Jascenko, Gunars Duburs, Inna Inashkina, and Jekaterina Erenpreisa



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