Transient reprogramming of postnatal cardiomyocytes to a dedifferentiated state.
In contrast to mammals, lower vertebrates are capable of extraordinary myocardial regeneration thanks to the ability of their cardiomyocytes to undergo transient dedifferentiation and proliferation. Somatic cells can be temporarily reprogrammed to a proliferative, dedifferentiated state through forc...
| Main Authors: | , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2021-01-01
|
| Series: | PLoS ONE |
| Online Access: | https://doi.org/10.1371/journal.pone.0251054 |
| _version_ | 1818681973269331968 |
|---|---|
| author | Thomas Kisby Irene de Lázaro Maria Stylianou Giulio Cossu Kostas Kostarelos |
| author_facet | Thomas Kisby Irene de Lázaro Maria Stylianou Giulio Cossu Kostas Kostarelos |
| author_sort | Thomas Kisby |
| collection | DOAJ |
| description | In contrast to mammals, lower vertebrates are capable of extraordinary myocardial regeneration thanks to the ability of their cardiomyocytes to undergo transient dedifferentiation and proliferation. Somatic cells can be temporarily reprogrammed to a proliferative, dedifferentiated state through forced expression of Oct3/4, Sox2, Klf4 and c-Myc (OSKM). Here, we aimed to induce transient reprogramming of mammalian cardiomyocytes in vitro utilising an OSKM-encoding non-integrating vector. Reprogramming factor expression in postnatal rat and mouse cardiomyocytes triggered rapid but limited cell dedifferentiation. Concomitantly, a significant increase in cell viability, cell cycle related gene expression and Ki67 positive cells was observed consistent with an enhanced cell cycle activation. The transient nature of this partial reprogramming was confirmed as cardiomyocyte-specific cell morphology, gene expression and contractile activity were spontaneously recovered by day 15 after viral transduction. This study provides the first evidence that adenoviral OSKM delivery can induce partial reprogramming of postnatal cardiomyocytes. Therefore, adenoviral mediated transient reprogramming could be a novel and feasible strategy to recapitulate the regenerative mechanisms of lower vertebrates. |
| first_indexed | 2024-12-17T10:11:27Z |
| format | Article |
| id | doaj.art-4d0100f9e6fa43aba8eda8ba02a54f1d |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-17T10:11:27Z |
| publishDate | 2021-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-4d0100f9e6fa43aba8eda8ba02a54f1d2022-12-21T21:53:00ZengPublic Library of Science (PLoS)PLoS ONE1932-62032021-01-01165e025105410.1371/journal.pone.0251054Transient reprogramming of postnatal cardiomyocytes to a dedifferentiated state.Thomas KisbyIrene de LázaroMaria StylianouGiulio CossuKostas KostarelosIn contrast to mammals, lower vertebrates are capable of extraordinary myocardial regeneration thanks to the ability of their cardiomyocytes to undergo transient dedifferentiation and proliferation. Somatic cells can be temporarily reprogrammed to a proliferative, dedifferentiated state through forced expression of Oct3/4, Sox2, Klf4 and c-Myc (OSKM). Here, we aimed to induce transient reprogramming of mammalian cardiomyocytes in vitro utilising an OSKM-encoding non-integrating vector. Reprogramming factor expression in postnatal rat and mouse cardiomyocytes triggered rapid but limited cell dedifferentiation. Concomitantly, a significant increase in cell viability, cell cycle related gene expression and Ki67 positive cells was observed consistent with an enhanced cell cycle activation. The transient nature of this partial reprogramming was confirmed as cardiomyocyte-specific cell morphology, gene expression and contractile activity were spontaneously recovered by day 15 after viral transduction. This study provides the first evidence that adenoviral OSKM delivery can induce partial reprogramming of postnatal cardiomyocytes. Therefore, adenoviral mediated transient reprogramming could be a novel and feasible strategy to recapitulate the regenerative mechanisms of lower vertebrates.https://doi.org/10.1371/journal.pone.0251054 |
| spellingShingle | Thomas Kisby Irene de Lázaro Maria Stylianou Giulio Cossu Kostas Kostarelos Transient reprogramming of postnatal cardiomyocytes to a dedifferentiated state. PLoS ONE |
| title | Transient reprogramming of postnatal cardiomyocytes to a dedifferentiated state. |
| title_full | Transient reprogramming of postnatal cardiomyocytes to a dedifferentiated state. |
| title_fullStr | Transient reprogramming of postnatal cardiomyocytes to a dedifferentiated state. |
| title_full_unstemmed | Transient reprogramming of postnatal cardiomyocytes to a dedifferentiated state. |
| title_short | Transient reprogramming of postnatal cardiomyocytes to a dedifferentiated state. |
| title_sort | transient reprogramming of postnatal cardiomyocytes to a dedifferentiated state |
| url | https://doi.org/10.1371/journal.pone.0251054 |
| work_keys_str_mv | AT thomaskisby transientreprogrammingofpostnatalcardiomyocytestoadedifferentiatedstate AT irenedelazaro transientreprogrammingofpostnatalcardiomyocytestoadedifferentiatedstate AT mariastylianou transientreprogrammingofpostnatalcardiomyocytestoadedifferentiatedstate AT giuliocossu transientreprogrammingofpostnatalcardiomyocytestoadedifferentiatedstate AT kostaskostarelos transientreprogrammingofpostnatalcardiomyocytestoadedifferentiatedstate |