Format

Send to

Choose Destination
Nat Commun. 2018 Sep 10;9(1):3670. doi: 10.1038/s41467-018-06068-6.

Dynamics of cellular states of fibro-adipogenic progenitors during myogenesis and muscular dystrophy.

Author information

1
Development, Aging and Regeneration Program at Sanford Burnham Prebys Medical Discovery Institute, La Jolla, CA, 92037, USA. barboramalecova22@gmail.com.
2
Avidity Biosciences LLC, La Jolla, CA, 92037, USA. barboramalecova22@gmail.com.
3
Development, Aging and Regeneration Program at Sanford Burnham Prebys Medical Discovery Institute, La Jolla, CA, 92037, USA.
4
Monoceros Biosystems LLC, San Diego, CA, 92172, USA.
5
IRCCS Fondazione Santa Lucia, 00142, Rome, Italy.
6
Department of Biology, University of Rome Tor Vergata, 00173, Rome, Italy.
7
Flow Cytometry Core, Sanford Burnham Prebys Medical Discovery Institute, La Jolla, CA, 92037, USA.
8
Department of Life Sciences, University of Modena and Reggio Emilia, Modena, 41125, Italy.
9
Sorbonne Université, INSERM UMRS974, Association Institut de Myologie, Centre de Recherche en Myologie, 75013, Paris, France.
10
Department of Biology and Biotechnology "Charles Darwin", Sapienza University, Rome, 00185, Italy.
11
Institute of Cell Biology and Neurobiology (IBCN), National Research Council of Italy (CNR), 00143, Rome, Italy.
12
Development, Aging and Regeneration Program at Sanford Burnham Prebys Medical Discovery Institute, La Jolla, CA, 92037, USA. lpuri@sbpdiscovery.org.
13
IRCCS Fondazione Santa Lucia, 00142, Rome, Italy. lpuri@sbpdiscovery.org.

Abstract

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 Tie2high or Tie2low and Tie2low/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.

PMID:
30202063
PMCID:
PMC6131350
DOI:
10.1038/s41467-018-06068-6
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Nature Publishing Group Icon for PubMed Central
Loading ...
Support Center