Dynamics of cellular states of fibro-adipogenic progenitors during myogenesis and muscular dystrophy
| Autor: | Amy Cortez, Chiara Nicoletti, Silvio Bicciato, Lorenzo Giordani, Usue Etxaniz, Luca Madaro, Marco De Bardi, Pier Lorenzo Puri, Barbora Malecova, Alessio Torcinaro, Magda Passafaro, Sole Gatto, Francesca De Santa |
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| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
Male
0301 basic medicine Genetics and Molecular Biology (all) physics and astronomy (all) Duchenne muscular dystrophy Cellular differentiation General Physics and Astronomy Muscle Development Biochemistry Mice chemistry (all) biochemistry genetics and molecular biology (all) Muscular dystrophy lcsh:Science Mice Inbred ICR Adipogenesis Multidisciplinary Myogenesis Stem Cells Chemistry (all) Cell Differentiation Flow Cytometry Receptor TIE-2 Cell biology medicine.anatomical_structure medicine.symptom congenital hereditary and neonatal diseases and abnormalities Science Vascular Cell Adhesion Molecule-1 Inflammation Biology Article General Biochemistry Genetics and Molecular Biology 03 medical and health sciences Physics and Astronomy (all) medicine Animals Regeneration Muscle Skeletal neoplasms Sequence Analysis RNA Gene Expression Profiling Macrophages Regeneration (biology) Skeletal muscle General Chemistry medicine.disease digestive system diseases Mice Inbred C57BL Muscular Dystrophy Duchenne Gene expression profiling 030104 developmental biology Mice Inbred mdx lcsh:Q Biochemistry Genetics and Molecular Biology (all) |
| Zdroj: | Nature Communications, Vol 9, Iss 1, Pp 1-12 (2018) Nature Communications |
| Popis: | 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. Fibro-adipogenic progenitors (FAPs) resident in skeletal muscle are involved in both regeneration and maladaptive processes. Here, the authors identify subpopulations of FAPs with biological activities implicated in physiological muscle repair that are altered in pathological conditions such as muscular dystrophies. |
| Databáze: | OpenAIRE |
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