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Cripto shapes macrophage plasticity and restricts EndMT in injured and diseased skeletal muscle

Iavarone Francescopaolo; Guardiola Ombretta; Scagliola Alessandra; Andolfi Gennaro; Esposito Federica; Serrano Antonio; Perdiguero Eusebio; Brunelli Silvia; Muñoz‐Cánoves Pura; Minchiotti Gabriella


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  <identifier identifierType="URL">https://zenodo.org/record/5584584</identifier>
  <creators>
    <creator>
      <creatorName>Iavarone Francescopaolo</creatorName>
      <affiliation>Stem Cell Fate Laboratory, CNR, Institute of Genetics and Biophysics "A. Buzzati-Traverso", Naples, Italy.</affiliation>
    </creator>
    <creator>
      <creatorName>Guardiola Ombretta</creatorName>
      <affiliation>Stem Cell Fate Laboratory, CNR, Institute of Genetics and Biophysics "A. Buzzati-Traverso", Naples, Italy.</affiliation>
    </creator>
    <creator>
      <creatorName>Scagliola Alessandra</creatorName>
      <affiliation>School of Medicine and Surgery, University of Milano-Bicocca, Monza, Italy.</affiliation>
    </creator>
    <creator>
      <creatorName>Andolfi Gennaro</creatorName>
      <affiliation>Stem Cell Fate Laboratory, CNR, Institute of Genetics and Biophysics "A. Buzzati-Traverso", Naples, Italy.</affiliation>
    </creator>
    <creator>
      <creatorName>Esposito Federica</creatorName>
      <affiliation>Stem Cell Fate Laboratory, CNR, Institute of Genetics and Biophysics "A. Buzzati-Traverso", Naples, Italy.</affiliation>
    </creator>
    <creator>
      <creatorName>Serrano Antonio</creatorName>
      <affiliation>Cell Biology Group, Department of Experimental and Health Sciences, Pompeu Fabra University (UPF), CIBER on Neurodegenerative Diseases (CIBERNED), Barcelona, Spain</affiliation>
    </creator>
    <creator>
      <creatorName>Perdiguero Eusebio</creatorName>
      <affiliation>Cell Biology Group, Department of Experimental and Health Sciences, Pompeu Fabra University (UPF), CIBER on Neurodegenerative Diseases (CIBERNED), Barcelona, Spain</affiliation>
    </creator>
    <creator>
      <creatorName>Brunelli Silvia</creatorName>
      <affiliation>School of Medicine and Surgery, University of Milano-Bicocca, Monza, Italy.</affiliation>
    </creator>
    <creator>
      <creatorName>Muñoz‐Cánoves Pura</creatorName>
      <affiliation>Cell Biology Group, Department of Experimental and Health Sciences, Pompeu Fabra University (UPF), CIBER on Neurodegenerative Diseases (CIBERNED), Barcelona, Spain.  Institució Catalana de Recerca i Estudis Avançats (ICREA), Barcelona, Spain.  Centro Nacional de Investigaciones Cardiovasculares (CNIC), Madrid, Spain.</affiliation>
    </creator>
    <creator>
      <creatorName>Minchiotti Gabriella</creatorName>
      <affiliation>Stem Cell Fate Laboratory, CNR, Institute of Genetics and Biophysics "A. Buzzati-Traverso", Naples, Italy.</affiliation>
    </creator>
  </creators>
  <titles>
    <title>Cripto shapes macrophage plasticity and restricts EndMT in injured and diseased skeletal muscle</title>
  </titles>
  <publisher>Zenodo</publisher>
  <publicationYear>2020</publicationYear>
  <dates>
    <date dateType="Issued">2020-02-27</date>
  </dates>
  <resourceType resourceTypeGeneral="JournalArticle"/>
  <alternateIdentifiers>
    <alternateIdentifier alternateIdentifierType="url">https://zenodo.org/record/5584584</alternateIdentifier>
  </alternateIdentifiers>
  <relatedIdentifiers>
    <relatedIdentifier relatedIdentifierType="DOI" relationType="IsIdenticalTo">10.15252/embr.201949075</relatedIdentifier>
    <relatedIdentifier relatedIdentifierType="URL" relationType="IsPartOf">https://zenodo.org/communities/upgrade-h2020-project</relatedIdentifier>
  </relatedIdentifiers>
  <rightsList>
    <rights rightsURI="https://creativecommons.org/licenses/by/4.0/legalcode">Creative Commons Attribution 4.0 International</rights>
    <rights rightsURI="info:eu-repo/semantics/openAccess">Open Access</rights>
  </rightsList>
  <descriptions>
    <description descriptionType="Abstract">&lt;p&gt;&lt;strong&gt;Abstract&lt;/strong&gt;&lt;/p&gt;

&lt;p&gt;Macrophages are characterized by a high plasticity in response to changes in tissue microenvironment, which allows them to acquire different phenotypes and to exert essential functions in complex processes, such as tissue regeneration. Here, we report that the membrane protein Cripto plays a key role in shaping macrophage plasticity in skeletal muscle during regeneration and disease. Conditional deletion of Cripto in the myeloid lineage (Cripto&lt;sup&gt;My-LOF&lt;/sup&gt;) perturbs MP plasticity in acutely injured muscle and in mouse models of Duchenne muscular dystrophy (mdx). Specifically, Cripto&lt;sup&gt;My-LOF&lt;/sup&gt;&amp;nbsp;macrophages infiltrate the muscle, but fail to properly expand as anti-inflammatory CD206&lt;sup&gt;+&lt;/sup&gt;&amp;nbsp;macrophages, which is due, at least in part, to aberrant activation of TGF&amp;beta;/Smad signaling. This reduction in macrophage plasticity disturbs vascular remodeling by increasing Endothelial-to-Mesenchymal Transition (EndMT), reduces muscle regenerative potential, and leads to an exacerbation of the dystrophic phenotype. Thus, in muscle-infiltrating macrophages, Cripto is required to promote the expansion of the CD206&lt;sup&gt;+&lt;/sup&gt;&amp;nbsp;anti-inflammatory macrophage type and to restrict the EndMT process, providing a direct functional link between this macrophage population and endothelial cells.&lt;/p&gt;</description>
  </descriptions>
  <fundingReferences>
    <fundingReference>
      <funderName>European Commission</funderName>
      <funderIdentifier funderIdentifierType="Crossref Funder ID">10.13039/100010661</funderIdentifier>
      <awardNumber awardURI="info:eu-repo/grantAgreement/EC/H2020/825825/">825825</awardNumber>
      <awardTitle>Unlocking Precision Gene Therapy</awardTitle>
    </fundingReference>
  </fundingReferences>
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