Transient reprogramming of postnatal cardiomyocytes to a dedifferentiated state
Kisby, Thomas (University of Manchester. Nanomedicine Lab)
de Lázaro, Irene (University of Manchester. Nanomedicine Lab)
Stylianou, Maria (University of Manchester. Nanomedicine Lab)
Cossu, Giulio (University of Manchester. Division of Cell Matrix Biology and Regenerative Medicine)
Kostarelos, Kostas (Institut Català de Nanociència i Nanotecnologia)

Data:	2021
Resum:	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.
Drets:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Llengua:	Anglès
Document:	Article ; recerca ; Versió publicada
Matèria:	Animals ; Cell Cycle ; Cell Dedifferentiation ; Cell Survival ; Cells, Cultured ; Cellular Reprogramming ; Gene Expression ; Ki-67 Antigen ; Mammals ; Mice ; Mice, Inbred C57BL ; Myocytes, Cardiac ; Rats ; Rats, Sprague-Dawley
Publicat a:	PloS one, Vol. 16, Issue 5 (May 2021) , p. e0251054, ISSN 1932-6203

DOI: 10.1371/journal.pone.0251054
PMID: 33951105

22 p, 4.5 MB

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