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

Milica Marinkovic; Claudia Fuoco; Francesca Sacco; Andrea Cerquone Perpetuini; Giulio Giuliani; Elisa Micarelli; Theodora Pavlidou; Lucia Lisa Petrilli; Alessio Reggio; Federica Riccio; Filomena Spada; Simone Vumbaca; Alessandro Zuccotti; Luisa Castagnoli; Matthias Mann; Cesare Gargioli; Gianni Cesareni

doi:10.26508/lsa.201900437

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

Milica Marinkovic, Claudia Fuoco, Francesca Sacco, Andrea Cerquone Perpetuini, Giulio Giuliani, Elisa Micarelli, Theodora Pavlidou, Lucia Lisa Petrilli, Alessio Reggio, Federica Riccio, Filomena Spada, Simone Vumbaca, Alessandro Zuccotti, Luisa Castagnoli, Matthias Mann, Cesare Gargioli, Gianni Cesareni

14 Citations (Scopus)

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.

Original language	English
Journal	Life Science Alliance
Volume	2
Issue number	3
ISSN	2575-1077
DOIs	https://doi.org/10.26508/lsa.201900437
Publication status	Published - Jun 2019
Externally published	Yes

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10.26508/lsa.201900437

e201900437.full.pdfFinal published version, 3.4 MBLicence: CC BY

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Marinkovic, M., Fuoco, C., Sacco, F., Cerquone Perpetuini, A., Giuliani, G., Micarelli, E., Pavlidou, T., Petrilli, L. L., Reggio, A., Riccio, F., Spada, F., Vumbaca, S., Zuccotti, A., Castagnoli, L., Mann, M., Gargioli, C., & Cesareni, G. (2019). Fibro-adipogenic progenitors of dystrophic mice are insensitive to NOTCH regulation of adipogenesis. Life Science Alliance, 2(3). https://doi.org/10.26508/lsa.201900437

Marinkovic, M, Fuoco, C, Sacco, F, Cerquone Perpetuini, A, Giuliani, G, Micarelli, E, Pavlidou, T, Petrilli, LL, Reggio, A, Riccio, F, Spada, F, Vumbaca, S, Zuccotti, A, Castagnoli, L, Mann, M, Gargioli, C & Cesareni, G 2019, 'Fibro-adipogenic progenitors of dystrophic mice are insensitive to NOTCH regulation of adipogenesis', Life Science Alliance, vol. 2, no. 3. https://doi.org/10.26508/lsa.201900437

@article{98a5e58f8da94a9cbe10168fe80dfbb8,

title = "Fibro-adipogenic progenitors of dystrophic mice are insensitive to NOTCH regulation of adipogenesis",

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.",

author = "Milica Marinkovic and Claudia Fuoco and Francesca Sacco and {Cerquone Perpetuini}, Andrea and Giulio Giuliani and Elisa Micarelli and Theodora Pavlidou and Petrilli, {Lucia Lisa} and Alessio Reggio and Federica Riccio and Filomena Spada and Simone Vumbaca and Alessandro Zuccotti and Luisa Castagnoli and Matthias Mann and Cesare Gargioli and Gianni Cesareni",

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year = "2019",

month = jun,

doi = "10.26508/lsa.201900437",

language = "English",

volume = "2",

journal = "Life Science Alliance",

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TY - JOUR

T1 - Fibro-adipogenic progenitors of dystrophic mice are insensitive to NOTCH regulation of adipogenesis

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

PY - 2019/6

Y1 - 2019/6

N2 - 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.

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.

U2 - 10.26508/lsa.201900437

DO - 10.26508/lsa.201900437

M3 - Journal article

C2 - 31239312

SN - 2575-1077

VL - 2

JO - Life Science Alliance

JF - Life Science Alliance

IS - 3

ER -

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

Abstract

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