Web of Science: 5 citations, Scopus: 5 citations, Google Scholar: citations,
Muscle cell identity requires Pax7-mediated lineage-specific DNA demethylation
Carrió Gaspar, Elvira ((Institut Germans Trias i Pujol. Institut de Medicina Predictiva i Personalitzada del Càncer)
Magli, Alessandro (Lillehei Heart Institute (Minneapolis, Estats Units d'Amèrica))
Muñoz, Mar (Institut Germans Trias i Pujol. Institut de Medicina Predictiva i Personalitzada del Càncer)
Peinado Morales, Miguel Á. (Miguel Ángel) (Institut Germans Trias i Pujol. Institut de Medicina Predictiva i Personalitzada del Càncer)
Perlingeiro, Rita (Lillehei Heart Institute (Minneapolis, Estats Units d'Amèrica))
Suelves Esteban, Mònica (Institut Germans Trias i Pujol. Institut de Medicina Predictiva i Personalitzada del Càncer)

Date: 2016
Abstract: BACKGROUND: Skeletal muscle stem cells enable the formation, growth, maintenance, and regeneration of skeletal muscle throughout life. The regeneration process is compromised in several pathological conditions, and muscle progenitors derived from pluripotent stem cells have been suggested as a potential therapeutic source for tissue replacement. DNA methylation is an important epigenetic mechanism in the setting and maintenance of cellular identity, but its role in stem cell determination towards the myogenic lineage is unknown. Here we addressed the DNA methylation dynamics of the major genes orchestrating the myogenic determination and differentiation programs in embryonic stem (ES) cells, their Pax7-induced myogenic derivatives, and muscle stem cells in proliferating and differentiating conditions. RESULTS: Our data showed a common muscle-specific DNA demethylation signature required to acquire and maintain the muscle-cell identity. This specific-DNA demethylation is Pax7-mediated, and it is a prime event in muscle stem cells gene activation. Notably, downregulation of the demethylation-related enzyme Apobec2 in ES-derived myogenic precursors reduced myogenin-associated DNA demethylation and dramatically impaired the expression of differentiation markers and, ultimately, muscle differentiation. CONCLUSIONS: Our results underscore DNA demethylation as a key mechanism driving myogenesis and identify specific Pax7-mediated DNA demethylation signatures to acquire and maintain the muscle-cell identity. Additionally, we provide a panel of epigenetic markers for the efficient and safe generation of ES- and induced pluripotent stem cell (iPS)-derived myogenic progenitors for therapeutic applications.
Note: Número d'acord de subvenció MINECO/SAF2012-37427
Note: Número d'acord de subvenció MINECO/SAF2011-23638
Note: Número d'acord de subvenció MINECO/SAF2015-64521
Note: Número d'acord de subvenció AGAUR/2009/SGR-1356
Note: Número d'acord de subvenció NIH/R01AR055299
Note: Altres ajuts: Minnesota Regenerative Medicine grant (MRM 2015 PDSCH 003)
Rights: 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. Creative Commons
Language: Anglès.
Document: article ; recerca ; publishedVersion
Subject: Apobec2 ; Cellular identity ; DNA methylation ; Epimarkers ; Myogenesis ; Pax7-induced ESCs
Published in: BMC biology, Vol. 14, Núm. 30 (2016) , ISSN 1741-7007

DOI: 10.1186/s12915-016-0250-9
PMID: 27075038


15 p, 2.3 MB

The record appears in these collections:
Research literature > UAB research groups literature > Research Centres and Groups (scientific output) > Health sciences and biosciences > Institut d'Investigació en Ciencies de la Salut Germans Trias i Pujol (IGTP)
Articles > Research articles
Articles > Published articles

 Record created 2017-05-18, last modified 2019-11-08



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