Journal
NATURE COMMUNICATIONS
Volume 9, Issue -, Pages -Publisher
NATURE RESEARCH
DOI: 10.1038/s41467-018-06068-6
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Funding
- NIH P30 pilot grant [P30AR061303]
- CIRM training grant [TG2-01162]
- NIH [P30AR061303, R01AR056712, R01AR052779]
- MDA
- AFM
- EPIGEN grant
- EPIGEN
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Fibro-adipogenic progenitors (FAPs) are currently defined by their anatomical position, expression of non-specific membrane-associated proteins, and ability to adopt multiple lineages in vitro. Gene expression analysis at single-cell level reveals that FAPs undergo dynamic transitions through a spectrum of cell states that can be identified by differential expression levels of Tie2 and Vcam1. Different patterns of Vcam1-negative Tie2(high) or Tie2(low) and Tie2(low)/Vcam1-expressing FAPs are detected during neonatal myogenesis, response to acute injury and Duchenne Muscular Dystrophy (DMD). RNA sequencing analysis identified cell state-specific transcriptional profiles that predict functional interactions with satellite and inflammatory cells. In particular, Vcam1-expressing FAPs, which exhibit a pro-fibrotic expression profile, are transiently activated by acute injury in concomitance with the inflammatory response. Aberrant persistence of Vcam1-expressing FAPs is detected in DMD muscles or upon macrophage depletion, and is associated with muscle fibrosis, thereby revealing how disruption of inflammation-regulated FAPs dynamics leads to a pathogenic outcome.
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