Dynamics of cellular states of fibro-adipogenic progenitors during myogenesis and muscular dystrophy
Barbora Malecova (),
Sole Gatto,
Usue Etxaniz,
Magda Passafaro,
Amy Cortez,
Chiara Nicoletti,
Lorenzo Giordani,
Alessio Torcinaro,
Marco Bardi,
Silvio Bicciato,
Francesca Santa,
Luca Madaro and
Pier Lorenzo Puri ()
Additional contact information
Barbora Malecova: Development, Aging and Regeneration Program at Sanford Burnham Prebys Medical Discovery Institute
Sole Gatto: Development, Aging and Regeneration Program at Sanford Burnham Prebys Medical Discovery Institute
Usue Etxaniz: Development, Aging and Regeneration Program at Sanford Burnham Prebys Medical Discovery Institute
Magda Passafaro: IRCCS Fondazione Santa Lucia
Amy Cortez: Flow Cytometry Core, Sanford Burnham Prebys Medical Discovery Institute
Chiara Nicoletti: Development, Aging and Regeneration Program at Sanford Burnham Prebys Medical Discovery Institute
Lorenzo Giordani: Development, Aging and Regeneration Program at Sanford Burnham Prebys Medical Discovery Institute
Alessio Torcinaro: Sapienza University
Marco Bardi: IRCCS Fondazione Santa Lucia
Silvio Bicciato: University of Modena and Reggio Emilia
Francesca Santa: Sapienza University
Luca Madaro: IRCCS Fondazione Santa Lucia
Pier Lorenzo Puri: Development, Aging and Regeneration Program at Sanford Burnham Prebys Medical Discovery Institute
Nature Communications, 2018, vol. 9, issue 1, 1-12
Abstract:
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.
Date: 2018
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Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:9:y:2018:i:1:d:10.1038_s41467-018-06068-6
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DOI: 10.1038/s41467-018-06068-6
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