PW1/Peg3 expression regulates key properties that determine mesoangioblast stem cell competence.
Mesoangioblasts are vessel-associated progenitor cells that show therapeutic promise for the treatment of muscular dystrophy. Mesoangioblasts have the ability to undergo skeletal muscle differentiation and cross the blood vessel wall regardless of the developmental stage at which they are isolated. Here we show that PW1/Peg3 is expressed at high levels in mesoangioblasts obtained from mouse, dog and human tissues and its level of expression correlates with their myogenic competence. Silencing PW1/Peg3 markedly inhibits myogenic potential of mesoangioblasts in vitro through MyoD degradation. Moreover, lack of PW1/Peg3 abrogates mesoangioblast ability to cross the vessel wall and to engraft into damaged myofibres through the modulation of the junctional adhesion molecule-A. We conclude that PW1/Peg3 function is essential for conferring proper mesoangioblast competence and that the determination of PW1/Peg3 levels in human mesoangioblasts may serve as a biomarker to identify the best donor populations for therapeutic application in muscular dystrophies.
Department of BioSciences, University of Milan, 20133 Milan, Italy.
Chiara
C
Bonfanti
Department of BioSciences, University of Milan, 20133 Milan, Italy.
Giuliana
G
Rossi
Department of Cell and Developmental Biology, University College London, 21 University Street, London WC1E 6DE, UK.
Francesco Saverio
FS
Tedesco
IFOM, FIRC Institute of Molecular Oncology, 20139 Milan, Italy.
Monica
M
Giannotta
1] Department of Cell and Developmental Biology, University College London, 21 University Street, London WC1E 6DE, UK [2] Institute of Child Health, University College London, 30 Guilford Street, London WC1N 1EH, UK.
Sara
S
Benedetti
San Raffaele Hospital, Division of Neuroscience-INSPE, via Olgettina 58, 20132 Milan, Italy.
Rossana
R
Tonlorenzi
Department of BioSciences, University of Milan, 20133 Milan, Italy.
Stefania
S
Antonini
Stem Cells and Regenerative Medicine, ICAN UMRS 1166 Inserm/Sorbonne University (UPMC ParisVI), 75634 Paris, France.
Giovanna
G
Marazzi
1] Department of BioSciences, University of Milan, 20133 Milan, Italy [2] IFOM, FIRC Institute of Molecular Oncology, 20139 Milan, Italy.
Elisabetta
E
Dejana
Stem Cells and Regenerative Medicine, ICAN UMRS 1166 Inserm/Sorbonne University (UPMC ParisVI), 75634 Paris, France.
David
D
Sassoon
1] Department of BioSciences, University of Milan, 20133 Milan, Italy [2] Department of Cell and Developmental Biology, University College London, 21 University Street, London WC1E 6DE, UK [3] Institute of Inflammation and Repair, University of Manchester, Oxford Road, Manchester M13 9PL, UK.
Giulio
G
Cossu
Department of BioSciences, University of Milan, 20133 Milan, Italy.
Graziella
G
Messina
D000818:Animals; D015415:Biomarkers / Q000378:metabolism*; D001808:Blood Vessels / Q000166:cytology*; D015153:Blotting, Western; D002478:Cells, Cultured; D047369:Chromatin Immunoprecipitation; D017931:DNA Primers / Q000235:genetics; D004285:Dogs; D020868:Gene Silencing; D005822:Genetic Vectors / Q000235:genetics; D006801:Humans; D051741:Kruppel-Like Transcription Factors / Q000235:genetics / Q000378:metabolism*; D008156:Luciferases; D051379:Mice; D008856:Microscopy, Fluorescence; D024510:Muscle Development / Q000502:physiology; D009136:Muscular Dystrophies / Q000628:therapy; D017570:MyoD Protein / Q000378:metabolism; D012190:Retroviridae; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013234:Stem Cells / Q000502:physiology*
D015415:Biomarkers; D017931:DNA Primers; D051741:Kruppel-Like Transcription Factors; D017570:MyoD Protein; C097901:Peg3 protein, mouse; D008156:Luciferases