RT Journal Article
SR Electronic
T1 Fibro-adipogenic progenitors of dystrophic mice are insensitive to NOTCH regulation of adipogenesis
JF Life Science Alliance
JO Life Sci. Alliance
FD Life Science Alliance LLC
SP e201900437
DO 10.26508/lsa.201900437
VO 2
IS 3
A1 Milica Marinkovic
A1 Claudia Fuoco
A1 Francesca Sacco
A1 Andrea Cerquone Perpetuini
A1 Giulio Giuliani
A1 Elisa Micarelli
A1 Theodora Pavlidou
A1 Lucia Lisa Petrilli
A1 Alessio Reggio
A1 Federica Riccio
A1 Filomena Spada
A1 Simone Vumbaca
A1 Alessandro Zuccotti
A1 Luisa Castagnoli
A1 Matthias Mann
A1 Cesare Gargioli
A1 Gianni Cesareni
YR 2019
UL https://www.life-science-alliance.org/content/2/3/e201900437.abstract
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.