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Fibro-adipogenic progenitors of dystrophic mice are insensitive to NOTCH regulation of adipogenesis

Fibro-adipogenic progenitors (FAPs) promote satellite cell differentiation in adult skeletal muscle regeneration. However, in pathological conditions, FAPs are responsible for fibrosis and fatty infiltrations. Here we show that the NOTCH pathway negatively modulates FAP differentiation both in vitro...

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Autores principales: Marinkovic, Milica, Fuoco, Claudia, Sacco, Francesca, Cerquone Perpetuini, Andrea, Giuliani, Giulio, Micarelli, Elisa, Pavlidou, Theodora, Petrilli, Lucia Lisa, Reggio, Alessio, Riccio, Federica, Spada, Filomena, Vumbaca, Simone, Zuccotti, Alessandro, Castagnoli, Luisa, Mann, Matthias, Gargioli, Cesare, Cesareni, Gianni
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Life Science Alliance LLC 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6599969/
https://www.ncbi.nlm.nih.gov/pubmed/31239312
http://dx.doi.org/10.26508/lsa.201900437
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author Marinkovic, Milica
Fuoco, Claudia
Sacco, Francesca
Cerquone Perpetuini, Andrea
Giuliani, Giulio
Micarelli, Elisa
Pavlidou, Theodora
Petrilli, Lucia Lisa
Reggio, Alessio
Riccio, Federica
Spada, Filomena
Vumbaca, Simone
Zuccotti, Alessandro
Castagnoli, Luisa
Mann, Matthias
Gargioli, Cesare
Cesareni, Gianni
author_facet Marinkovic, Milica
Fuoco, Claudia
Sacco, Francesca
Cerquone Perpetuini, Andrea
Giuliani, Giulio
Micarelli, Elisa
Pavlidou, Theodora
Petrilli, Lucia Lisa
Reggio, Alessio
Riccio, Federica
Spada, Filomena
Vumbaca, Simone
Zuccotti, Alessandro
Castagnoli, Luisa
Mann, Matthias
Gargioli, Cesare
Cesareni, Gianni
author_sort Marinkovic, Milica
collection PubMed
description Fibro-adipogenic progenitors (FAPs) promote satellite cell differentiation in adult skeletal muscle regeneration. However, in pathological conditions, FAPs are responsible for fibrosis and fatty infiltrations. Here we show that the NOTCH pathway negatively modulates FAP differentiation both in vitro and in vivo. However, FAPs isolated from young dystrophin-deficient mdx mice are insensitive to this control mechanism. An unbiased mass spectrometry–based proteomic analysis of FAPs from muscles of wild-type and mdx mice suggested that the synergistic cooperation between NOTCH and inflammatory signals controls FAP differentiation. Remarkably, we demonstrated that factors released by hematopoietic cells restore the sensitivity to NOTCH adipogenic inhibition in mdx FAPs. These results offer a basis for rationalizing pathological ectopic fat infiltrations in skeletal muscle and may suggest new therapeutic strategies to mitigate the detrimental effects of fat depositions in muscles of dystrophic patients.
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spelling pubmed-65999692019-07-10 Fibro-adipogenic progenitors of dystrophic mice are insensitive to NOTCH regulation of adipogenesis Marinkovic, Milica Fuoco, Claudia Sacco, Francesca Cerquone Perpetuini, Andrea Giuliani, Giulio Micarelli, Elisa Pavlidou, Theodora Petrilli, Lucia Lisa Reggio, Alessio Riccio, Federica Spada, Filomena Vumbaca, Simone Zuccotti, Alessandro Castagnoli, Luisa Mann, Matthias Gargioli, Cesare Cesareni, Gianni Life Sci Alliance Research Articles Fibro-adipogenic progenitors (FAPs) promote satellite cell differentiation in adult skeletal muscle regeneration. However, in pathological conditions, FAPs are responsible for fibrosis and fatty infiltrations. Here we show that the NOTCH pathway negatively modulates FAP differentiation both in vitro and in vivo. However, FAPs isolated from young dystrophin-deficient mdx mice are insensitive to this control mechanism. An unbiased mass spectrometry–based proteomic analysis of FAPs from muscles of wild-type and mdx mice suggested that the synergistic cooperation between NOTCH and inflammatory signals controls FAP differentiation. Remarkably, we demonstrated that factors released by hematopoietic cells restore the sensitivity to NOTCH adipogenic inhibition in mdx FAPs. These results offer a basis for rationalizing pathological ectopic fat infiltrations in skeletal muscle and may suggest new therapeutic strategies to mitigate the detrimental effects of fat depositions in muscles of dystrophic patients. Life Science Alliance LLC 2019-06-25 /pmc/articles/PMC6599969/ /pubmed/31239312 http://dx.doi.org/10.26508/lsa.201900437 Text en © 2019 Marinkovic et al. https://creativecommons.org/licenses/by/4.0/This article is available under a Creative Commons License (Attribution 4.0 International, as described at https://creativecommons.org/licenses/by/4.0/).
spellingShingle Research Articles
Marinkovic, Milica
Fuoco, Claudia
Sacco, Francesca
Cerquone Perpetuini, Andrea
Giuliani, Giulio
Micarelli, Elisa
Pavlidou, Theodora
Petrilli, Lucia Lisa
Reggio, Alessio
Riccio, Federica
Spada, Filomena
Vumbaca, Simone
Zuccotti, Alessandro
Castagnoli, Luisa
Mann, Matthias
Gargioli, Cesare
Cesareni, Gianni
Fibro-adipogenic progenitors of dystrophic mice are insensitive to NOTCH regulation of adipogenesis
title Fibro-adipogenic progenitors of dystrophic mice are insensitive to NOTCH regulation of adipogenesis
title_full Fibro-adipogenic progenitors of dystrophic mice are insensitive to NOTCH regulation of adipogenesis
title_fullStr Fibro-adipogenic progenitors of dystrophic mice are insensitive to NOTCH regulation of adipogenesis
title_full_unstemmed Fibro-adipogenic progenitors of dystrophic mice are insensitive to NOTCH regulation of adipogenesis
title_short Fibro-adipogenic progenitors of dystrophic mice are insensitive to NOTCH regulation of adipogenesis
title_sort fibro-adipogenic progenitors of dystrophic mice are insensitive to notch regulation of adipogenesis
topic Research Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6599969/
https://www.ncbi.nlm.nih.gov/pubmed/31239312
http://dx.doi.org/10.26508/lsa.201900437
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