Por favor, use este identificador para citar o enlazar a este item:
http://hdl.handle.net/10261/207530
COMPARTIR / EXPORTAR:
SHARE CORE BASE | |
Visualizar otros formatos: MARC | Dublin Core | RDF | ORE | MODS | METS | DIDL | DATACITE | |
Título: | The mutation m.13513G>A impairs cardiac function, favoring a neuroectoderm commitment, in a mutant-load dependent way |
Autor: | Galera‐Monge, Teresa; Zurita Díaz, Francisco; Garesse, Rafael CSIC ORCID; Gallardo, M. Esther CSIC ORCID | Palabras clave: | Cardiomyocytes Heteroplasmy iPSc Leigh syndrome Neuroectoderm |
Fecha de publicación: | nov-2019 | Editor: | Wiley-Liss | Citación: | Journal of Cellular Physiology 234(11): 19511-19522 (2019) | Resumen: | Mitochondrial disorders (MDs) arise as a result of a respiratory chain dysfunction. While some MDs can affect a single organ, many involve several organs, the brain being the most affected, followed by heart and/or muscle. Many of these diseases are associated with heteroplasmic mutations in the mitochondrial DNA (mtDNA). The proportion of mutated mtDNA must exceed a critical threshold to produce disease. Therefore, understanding how embryonic development determines the heteroplasmy level in each tissue could explain the organ susceptibility and the clinical heterogeneity observed in these patients. In this report, the dynamics of heteroplasmy and the influence in cardiac commitment of the mutational load of the m.13513G>A mutation has been analyzed. This mutation has been reported as a frequent cause of Leigh syndrome (LS) and is commonly associated with cardiac problems. In this report, induced pluripotent stem cell (iPSc) technology has been used to delve into the molecular mechanisms underlying cardiac disease in LS. When mutation m.13513G>A is above a threshold, iPSc‐derived cardiomyocytes (iPSc‐CMs) could not be obtained due to an inefficient epithelial‐mesenchymal transition. Surprisingly, these cells are redirected toward neuroectodermal lineages that would give rise to the brain. However, when mutation is below that threshold, dysfunctional CM are generated in a mutant‐load dependent way. We suggest that distribution of the m.13513G>A mutation during cardiac differentiation is not at random. We propose a possible explanation of why neuropathology is a frequent feature of MD, but cardiac involvement is not always present. | Versión del editor: | http://dx.doi.org/10.1002/jcp.28549 | URI: | http://hdl.handle.net/10261/207530 | DOI: | 10.1002/jcp.28549 | ISSN: | 0021-9541 | E-ISSN: | 1097-4652 |
Aparece en las colecciones: | (IIBM) Artículos |
Ficheros en este ítem:
Fichero | Descripción | Tamaño | Formato | |
---|---|---|---|---|
accesoRestringido.pdf | 15,38 kB | Adobe PDF | Visualizar/Abrir |
CORE Recommender
SCOPUSTM
Citations
12
checked on 27-mar-2024
WEB OF SCIENCETM
Citations
12
checked on 23-feb-2024
Page view(s)
128
checked on 28-mar-2024
Download(s)
24
checked on 28-mar-2024
Google ScholarTM
Check
Altmetric
Altmetric
NOTA: Los ítems de Digital.CSIC están protegidos por copyright, con todos los derechos reservados, a menos que se indique lo contrario.