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

Marinkovic, M., Fuoco, C., Sacco, F., Perpetuini, A. C., Giuliani, G., Micarelli, E., et al. (2019). Fibro-adipogenic progenitors of dystrophic mice are insensitive to NOTCH regulation of adipogenesis. Life Science Alliance, 2(3): e201900437. doi:10.26508/lsa.201900437.

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Item Permalink: http://hdl.handle.net/21.11116/0000-0004-8C60-2 Version Permalink: http://hdl.handle.net/21.11116/0000-0004-8C61-1
Genre: Journal Article

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 Creators:
Marinkovic, Milica1, Author
Fuoco, Claudia1, Author
Sacco, Francesca2, Author              
Perpetuini, Andrea Cerquone1, Author
Giuliani, Giulio1, Author
Micarelli, Elisa1, Author
Pavlidou, Theodora1, Author
Petrilli, Lucia Lisa1, Author
Reggio, Alessio1, Author
Riccio, Federica1, Author
Spada, Filomena1, Author
Vumbaca, Simone1, Author
Zuccotti, Alessandro1, Author
Castagnoli, Luisa1, Author
Mann, Matthias2, Author              
Gargioli, Cesare1, Author
Cesareni, Gianni1, Author
Affiliations:
1external, ou_persistent22              
2Mann, Matthias / Proteomics and Signal Transduction, Max Planck Institute of Biochemistry, Max Planck Society, ou_1565159              

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Free keywords: SKELETAL-MUSCLE; PPAR-GAMMA; STEM-CELLS; MESENCHYMAL PROGENITOR; SATELLITE CELLS; SELF-RENEWAL; MDX MICE; REGENERATION; REVEALS; INJURYLife Sciences & Biomedicine - Other Topics;
 Abstract: 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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Language(s): eng - English
 Dates: 2019
 Publication Status: Published online
 Pages: 17
 Publishing info: -
 Table of Contents: -
 Rev. Method: -
 Identifiers: ISI: 000473222200028
DOI: 10.26508/lsa.201900437
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Title: Life Science Alliance
Source Genre: Journal
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Publ. Info: 1 BUNGTOWN RD, COLD SPRING HARBOR, NY 11724 USA : LIFE SCIENCE ALLIANCE LLC
Pages: - Volume / Issue: 2 (3) Sequence Number: e201900437 Start / End Page: - Identifier: ISSN: 2575-1077