Self-Renewal Signalling in Presenescent Tetraploid IMR90 Cells
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 th...
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| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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Wiley
2011-01-01
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| Series: | Journal of Aging Research |
| Online Access: | http://dx.doi.org/10.4061/2011/103253 |
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| _version_ | 1832548780459687936 |
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| author | Anda Huna Kristine Salmina Elina Jascenko Gunars Duburs Inna Inashkina Jekaterina Erenpreisa |
| author_facet | Anda Huna Kristine Salmina Elina Jascenko Gunars Duburs Inna Inashkina Jekaterina Erenpreisa |
| author_sort | Anda Huna |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-b6a4bed28bc044f9b5bac8cda3f00201 |
| institution | Kabale University |
| issn | 2090-2212 |
| language | English |
| publishDate | 2011-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Journal of Aging Research |
| spelling | doaj-art-b6a4bed28bc044f9b5bac8cda3f002012025-02-03T06:13:09ZengWileyJournal of Aging Research2090-22122011-01-01201110.4061/2011/103253103253Self-Renewal Signalling in Presenescent Tetraploid IMR90 CellsAnda Huna0Kristine Salmina1Elina Jascenko2Gunars Duburs3Inna Inashkina4Jekaterina Erenpreisa5Latvian Biomedical Research and Study Centre, Ratsupites 1, 1067 Riga, LatviaLatvian Biomedical Research and Study Centre, Ratsupites 1, 1067 Riga, LatviaLatvian Institute of Organic Synthesis, Aizkraukles 21, 1006 Riga, LatviaLatvian Institute of Organic Synthesis, Aizkraukles 21, 1006 Riga, LatviaLatvian Biomedical Research and Study Centre, Ratsupites 1, 1067 Riga, LatviaLatvian Biomedical Research and Study Centre, Ratsupites 1, 1067 Riga, LatviaEndopolyploidy 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.http://dx.doi.org/10.4061/2011/103253 |
| spellingShingle | Anda Huna Kristine Salmina Elina Jascenko Gunars Duburs Inna Inashkina Jekaterina Erenpreisa Self-Renewal Signalling in Presenescent Tetraploid IMR90 Cells Journal of Aging Research |
| title | Self-Renewal Signalling in Presenescent Tetraploid IMR90 Cells |
| title_full | Self-Renewal Signalling in Presenescent Tetraploid IMR90 Cells |
| title_fullStr | Self-Renewal Signalling in Presenescent Tetraploid IMR90 Cells |
| title_full_unstemmed | Self-Renewal Signalling in Presenescent Tetraploid IMR90 Cells |
| title_short | Self-Renewal Signalling in Presenescent Tetraploid IMR90 Cells |
| title_sort | self renewal signalling in presenescent tetraploid imr90 cells |
| url | http://dx.doi.org/10.4061/2011/103253 |
| work_keys_str_mv | AT andahuna selfrenewalsignallinginpresenescenttetraploidimr90cells AT kristinesalmina selfrenewalsignallinginpresenescenttetraploidimr90cells AT elinajascenko selfrenewalsignallinginpresenescenttetraploidimr90cells AT gunarsduburs selfrenewalsignallinginpresenescenttetraploidimr90cells AT innainashkina selfrenewalsignallinginpresenescenttetraploidimr90cells AT jekaterinaerenpreisa selfrenewalsignallinginpresenescenttetraploidimr90cells |