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Epigenetic Trajectories of Aging and Reprogramming
The epigenetic landscape is remodeled with age, bringing about widespread consequences for cell function. With the revolutionary discoveries by Yamanaka and Takahashi, as well as those that built on this work, the transcription factors Oct4, Sox2, KLF4, and C-Myc (OSKM) can be expressed in a variety...
Autores principales: | , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Oxford University Press
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8681272/ http://dx.doi.org/10.1093/geroni/igab046.2508 |
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author | Niimi, Peter Levine, Morgan Meer, and Margarita |
author_facet | Niimi, Peter Levine, Morgan Meer, and Margarita |
author_sort | Niimi, Peter |
collection | PubMed |
description | The epigenetic landscape is remodeled with age, bringing about widespread consequences for cell function. With the revolutionary discoveries by Yamanaka and Takahashi, as well as those that built on this work, the transcription factors Oct4, Sox2, KLF4, and C-Myc (OSKM) can be expressed in a variety of cells, including fibroblasts, to make iPSCs. Once cells are reprogrammed, they show an erasure of epigenetic remodeling, suggesting an avenue to reverse aging. It has been recently shown that ectopic expression of three factors, OSK, can restore vision in mouse glaucoma model and reduces epigenetic age. It is not known the path epigenetic remodeling takes or whether all three factors, OSK, are required to remodel the epigenetic landscape. We hypothesize that during reprogramming, cells will reverse along a similar path they took during aging and eventually reverse along that path they took during differentiation. Alternatively, it may also be possible that cells take entirely new paths to reach a state of partial reprogramming or pluripotency. We used DNA methylation and RNA-seq as a multi-omics approach to map the trajectories cells make during aging, differentiation, and reprogramming. In human fibroblasts and hepatocytes, we tested the three-factor OSK mix, as well as pairwise factors OS, OK, and SK and individual Oct4, Sox2, and KLF4 for their effect on cell trajectories. This study provides a dynamic model for epigenetic changes in aging, differentiation, and reprogramming and highlights barriers and bottlenecks throughout the process. |
format | Online Article Text |
id | pubmed-8681272 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Oxford University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-86812722021-12-17 Epigenetic Trajectories of Aging and Reprogramming Niimi, Peter Levine, Morgan Meer, and Margarita Innov Aging Abstracts The epigenetic landscape is remodeled with age, bringing about widespread consequences for cell function. With the revolutionary discoveries by Yamanaka and Takahashi, as well as those that built on this work, the transcription factors Oct4, Sox2, KLF4, and C-Myc (OSKM) can be expressed in a variety of cells, including fibroblasts, to make iPSCs. Once cells are reprogrammed, they show an erasure of epigenetic remodeling, suggesting an avenue to reverse aging. It has been recently shown that ectopic expression of three factors, OSK, can restore vision in mouse glaucoma model and reduces epigenetic age. It is not known the path epigenetic remodeling takes or whether all three factors, OSK, are required to remodel the epigenetic landscape. We hypothesize that during reprogramming, cells will reverse along a similar path they took during aging and eventually reverse along that path they took during differentiation. Alternatively, it may also be possible that cells take entirely new paths to reach a state of partial reprogramming or pluripotency. We used DNA methylation and RNA-seq as a multi-omics approach to map the trajectories cells make during aging, differentiation, and reprogramming. In human fibroblasts and hepatocytes, we tested the three-factor OSK mix, as well as pairwise factors OS, OK, and SK and individual Oct4, Sox2, and KLF4 for their effect on cell trajectories. This study provides a dynamic model for epigenetic changes in aging, differentiation, and reprogramming and highlights barriers and bottlenecks throughout the process. Oxford University Press 2021-12-17 /pmc/articles/PMC8681272/ http://dx.doi.org/10.1093/geroni/igab046.2508 Text en © The Author(s) 2021. Published by Oxford University Press on behalf of The Gerontological Society of America. https://creativecommons.org/licenses/by/4.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) ), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Abstracts Niimi, Peter Levine, Morgan Meer, and Margarita Epigenetic Trajectories of Aging and Reprogramming |
title | Epigenetic Trajectories of Aging and Reprogramming |
title_full | Epigenetic Trajectories of Aging and Reprogramming |
title_fullStr | Epigenetic Trajectories of Aging and Reprogramming |
title_full_unstemmed | Epigenetic Trajectories of Aging and Reprogramming |
title_short | Epigenetic Trajectories of Aging and Reprogramming |
title_sort | epigenetic trajectories of aging and reprogramming |
topic | Abstracts |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8681272/ http://dx.doi.org/10.1093/geroni/igab046.2508 |
work_keys_str_mv | AT niimipeter epigenetictrajectoriesofagingandreprogramming AT levinemorgan epigenetictrajectoriesofagingandreprogramming AT meerandmargarita epigenetictrajectoriesofagingandreprogramming |