PT  - JOURNAL ARTICLE
AU  - Marinkovic, Milica
AU  - Fuoco, Claudia
AU  - Sacco, Francesca
AU  - Cerquone Perpetuini, Andrea
AU  - Giuliani, Giulio
AU  - Micarelli, Elisa
AU  - Pavlidou, Theodora
AU  - Petrilli, Lucia Lisa
AU  - Reggio, Alessio
AU  - Riccio, Federica
AU  - Spada, Filomena
AU  - Vumbaca, Simone
AU  - Zuccotti, Alessandro
AU  - Castagnoli, Luisa
AU  - Mann, Matthias
AU  - Gargioli, Cesare
AU  - Cesareni, Gianni
TI  - Fibro-adipogenic progenitors of dystrophic mice are insensitive to NOTCH regulation of adipogenesis
AID  - 10.26508/lsa.201900437
DP  - 2019 Jun 01
TA  - Life Science Alliance
PG  - e201900437
VI  - 2
IP  - 3
4099  - http://www.life-science-alliance.org/content/2/3/e201900437.short
4100  - http://www.life-science-alliance.org/content/2/3/e201900437.full
SO  - Life Sci. Alliance2019 Jun 01; 2
AB  - 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.