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Journal Article

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

MPS-Authors
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Sacco,  Francesca
Mann, Matthias / Proteomics and Signal Transduction, Max Planck Institute of Biochemistry, Max Planck Society;

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Mann,  Matthias
Mann, Matthias / Proteomics and Signal Transduction, Max Planck Institute of Biochemistry, Max Planck Society;

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Fulltext (public)

e201900437.full.pdf
(Publisher version), 4MB

Supplementary Material (public)

F1.ppt
(Supplementary material), 242KB

Citation

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.


Cite as: http://hdl.handle.net/21.11116/0000-0004-8C60-2
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.