Non-myogenic mesenchymal cells contribute to muscle degeneration in facioscapulohumeral muscular dystrophy patients.
Journal
Cell death & disease
ISSN: 2041-4889
Titre abrégé: Cell Death Dis
Pays: England
ID NLM: 101524092
Informations de publication
Date de publication:
16 09 2022
16 09 2022
Historique:
received:
03
05
2022
accepted:
05
09
2022
revised:
26
08
2022
entrez:
16
9
2022
pubmed:
17
9
2022
medline:
21
9
2022
Statut:
epublish
Résumé
Muscle-resident non-myogenic mesenchymal cells play key roles that drive successful tissue regeneration within the skeletal muscle stem cell niche. These cells have recently emerged as remarkable therapeutic targets for neuromuscular disorders, although to date they have been poorly investigated in facioscapulohumeral muscular dystrophy (FSHD). In this study, we characterised the non-myogenic mesenchymal stromal cell population in FSHD patients' muscles with signs of disease activity, identified by muscle magnetic resonance imaging (MRI), and compared them with those obtained from apparently normal muscles of FSHD patients and from muscles of healthy, age-matched controls. Our results showed that patient-derived cells displayed a distinctive expression pattern of mesenchymal markers, along with an impaired capacity to differentiate towards mature adipocytes in vitro, compared with control cells. We also demonstrated a significant expansion of non-myogenic mesenchymal cells (identified as CD201- or PDGFRA-expressing cells) in FSHD muscles with signs of disease activity, which correlated with the extent of intramuscular fibrosis. In addition, the accumulation of non-myogenic mesenchymal cells was higher in FSHD muscles that deteriorate more rapidly. Our results prompt a direct association between an accumulation, as well as an altered differentiation, of non-myogenic mesenchymal cells with muscle degeneration in FSHD patients. Elucidating the mechanisms and cellular interactions that are altered in the affected muscles of FSHD patients could be instrumental to clarify disease pathogenesis and identifying reliable novel therapeutic targets.
Identifiants
pubmed: 36114172
doi: 10.1038/s41419-022-05233-6
pii: 10.1038/s41419-022-05233-6
pmc: PMC9481542
doi:
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
793Informations de copyright
© 2022. The Author(s).
Références
Sci Rep. 2018 Nov 16;8(1):16957
pubmed: 30446688
Nat Commun. 2019 Jun 3;10(1):2430
pubmed: 31160583
Nat Cell Biol. 2010 Feb;12(2):143-52
pubmed: 20081842
J Neurol. 2022 Apr;269(4):2055-2063
pubmed: 34486074
Neurology. 2008 Sep 2;71(10):758-65
pubmed: 18765652
Methods. 2001 Dec;25(4):402-8
pubmed: 11846609
PLoS One. 2013 Sep 03;8(9):e73573
pubmed: 24019929
Cell Metab. 2021 Nov 2;33(11):2201-2214.e11
pubmed: 34678202
Trends Mol Med. 2022 Jan;28(1):8-11
pubmed: 34750068
J Cell Mol Med. 2010 Jan;14(1-2):275-89
pubmed: 18505476
Open Biol. 2021 Dec;11(12):210110
pubmed: 34875199
Front Physiol. 2021 Apr 20;12:673404
pubmed: 33959042
J Cell Sci. 2011 Nov 1;124(Pt 21):3654-64
pubmed: 22045730
Int J Mol Sci. 2022 Feb 11;23(4):
pubmed: 35216102
Science. 2010 Sep 24;329(5999):1650-3
pubmed: 20724583
Nat Cell Biol. 2018 Aug;20(8):917-927
pubmed: 30050118
J Biophys Biochem Cytol. 1961 Feb;9:493-5
pubmed: 13768451
Sci Rep. 2019 Mar 13;9(1):4360
pubmed: 30867438
J Clin Invest. 2017 Apr 3;127(4):1531-1545
pubmed: 28263188
Blood. 2014 Sep 4;124(10):1553-62
pubmed: 25049281
Mol Neurobiol. 2018 Apr;55(4):2959-2966
pubmed: 28456937
FEBS J. 2021 Jun 18;:
pubmed: 34143565
J Clin Invest. 2020 May 1;130(5):2465-2477
pubmed: 32250341
Cell Mol Life Sci. 2015 Jun;72(11):2135-56
pubmed: 25854633
Skelet Muscle. 2021 Jul 1;11(1):16
pubmed: 34210364
Handb Clin Neurol. 2018;148:541-548
pubmed: 29478599
Front Physiol. 2014 Feb 24;5:68
pubmed: 24605102
Front Physiol. 2019 Aug 21;10:1074
pubmed: 31496956
Nucleic Acids Res. 2015 Jul 1;43(W1):W566-70
pubmed: 25969447
Neuromuscul Disord. 2019 Nov;29(11):827-841
pubmed: 31727541
EMBO Rep. 2013 Dec;14(12):1062-72
pubmed: 24232182
Stem Cell Reports. 2016 Aug 9;7(2):263-78
pubmed: 27509136
Methods Mol Biol. 2018;1687:231-256
pubmed: 29067668
Orphanet J Rare Dis. 2021 Mar 12;16(1):129
pubmed: 33712050
J Cachexia Sarcopenia Muscle. 2019 Dec;10(6):1258-1265
pubmed: 31668022
Rare Dis. 2014 Dec 01;2(1):e974969
pubmed: 26942105
Cell Death Dis. 2014 Apr 17;5:e1186
pubmed: 24743741
Nat Commun. 2017 Sep 15;8(1):550
pubmed: 28916757
Cell Death Dis. 2015 Apr 23;6:e1733
pubmed: 25906156
J Cell Sci. 2013 Dec 15;126(Pt 24):5610-25
pubmed: 24101731
Heliyon. 2020 Jul 21;6(7):e04503
pubmed: 32728644
Cell Death Dis. 2015 Jul 23;6:e1830
pubmed: 26203859
PLoS One. 2012;7(6):e38779
pubmed: 22719944