In vivo transcriptomic profiling using cell encapsulation identifieseffector pathways of systemic aging

  1. Omid Mashinchian
  2. Xiaotong Hong
  3. Joris Michaud
  4. Eugenia Migliavacca
  5. Gregory Lefebvre
  6. Christophe Boss
  7. Filippo De Franceschi
  8. Emmeran Le Moal
  9. Jasmin Collerette-Tremblay
  10. Joan Isern
  11. Sylviane Metairon
  12. Frederic Raymond
  13. Patrick Descombes
  14. Nicolas Bouche
  15. Pura Muñoz-Cánoves
  16. Jerome N Feige  Is a corresponding author
  17. C Florian Bentzinger  Is a corresponding author
  1. Nestlé Research, Switzerland
  2. Université de Sherbrooke, Canada
  3. Centro Nacional de Investigaciones Cardiovasculares, Spain
  4. Pompeu Fabra University, Spain

Abstract

Sustained exposure to a young systemic environment rejuvenates aged organisms and promotes cellular function. However, due to the intrinsic complexity of tissues it remains challenging to pinpoint niche-independent effects of circulating factors on specific cell populations. Here we describe a method for the encapsulation of human and mouse skeletal muscle progenitors in diffusible polyethersulfone hollow fiber capsules that can be used to profile systemic aging in vivo independent of heterogeneous short-range tissue interactions. We observed that circulating long-range signaling factors in the old systemic environment lead to an activation of Myc and E2F transcription factors, induce senescence and suppress myogenic differentiation. Importantly, in vitro profiling using young and old serum in 2D culture does not capture all pathways deregulated in encapsulated cells in aged mice. Thus, in vivo transcriptomic profiling using cell encapsulation allows for the characterization of effector pathways of systemic aging with unparalleled accuracy.

Data availability

The data discussed in this publication have been deposited in NCBI's Gene Expression Omnibus (GEO). GEO Series accession numbers are GSE111401, GSE81096 and GSE193665.

The following data sets were generated
The following previously published data sets were used

Article and author information

Author details

  1. Omid Mashinchian

    Nestlé Institute of Health Sciences, Nestlé Research, Lausanne, Switzerland
    Competing interests
    Omid Mashinchian, Presently or previously employed by the Société des Produits Nestlé S.A., Switzerland.
  2. Xiaotong Hong

    Nestlé Institute of Health Sciences, Nestlé Research, Lausanne, Switzerland
    Competing interests
    Xiaotong Hong, Presently or previously employed by the Société des Produits Nestlé S.A., Switzerland.
  3. Joris Michaud

    Nestlé Institute of Health Sciences, Nestlé Research, Lausanne, Switzerland
    Competing interests
    Joris Michaud, Presently or previously employed by the Société des Produits Nestlé S.A., Switzerland.
  4. Eugenia Migliavacca

    Nestlé Institute of Health Sciences, Nestlé Research, Lausanne, Switzerland
    Competing interests
    Eugenia Migliavacca, Presently or previously employed by the Société des Produits Nestlé S.A., Switzerland.
  5. Gregory Lefebvre

    Nestlé Institute of Health Sciences, Nestlé Research, Lausanne, Switzerland
    Competing interests
    Gregory Lefebvre, Presently or previously employed by the Société des Produits Nestlé S.A., Switzerland.
  6. Christophe Boss

    Nestlé Institute of Health Sciences, Nestlé Research, Lausanne, Switzerland
    Competing interests
    Christophe Boss, Presently or previously employed by the Société des Produits Nestlé S.A., Switzerland.
  7. Filippo De Franceschi

    Nestlé Institute of Health Sciences, Nestlé Research, Lausanne, Switzerland
    Competing interests
    Filippo De Franceschi, Presently or previously employed by the Société des Produits Nestlé S.A., Switzerland.
  8. Emmeran Le Moal

    Département de Pharmacologie-Physiologie, Université de Sherbrooke, Sherbrooke, Canada
    Competing interests
    No competing interests declared.
  9. Jasmin Collerette-Tremblay

    Département de Pharmacologie-Physiologie, Université de Sherbrooke, Sherbrooke, Canada
    Competing interests
    No competing interests declared.
  10. Joan Isern

    Vascular Pathophysiology Area, Centro Nacional de Investigaciones Cardiovasculares, Madrid, Spain
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-1401-9779
  11. Sylviane Metairon

    Nestlé Institute of Health Sciences, Nestlé Research, Lausanne, Switzerland
    Competing interests
    Sylviane Metairon, Presently or previously employed by the Société des Produits Nestlé S.A., Switzerland.
  12. Frederic Raymond

    Nestlé Institute of Health Sciences, Nestlé Research, Lausanne, Switzerland
    Competing interests
    Frederic Raymond, Presently or previously employed by the Société des Produits Nestlé S.A., Switzerland.
  13. Patrick Descombes

    Nestlé Institute of Health Sciences, Nestlé Research, Lausanne, Switzerland
    Competing interests
    Patrick Descombes, Presently or previously employed by the Société des Produits Nestlé S.A., Switzerland.
  14. Nicolas Bouche

    Nestlé Institute of Health Sciences, Nestlé Research, Lausanne, Switzerland
    Competing interests
    Nicolas Bouche, Presently or previously employed by the Société des Produits Nestlé S.A., Switzerland.
  15. Pura Muñoz-Cánoves

    Department of Experimental and Health Sciences, Pompeu Fabra University, Barcelona, Spain
    Competing interests
    No competing interests declared.
  16. Jerome N Feige

    Nestlé Institute of Health Science, Nestlé Research, Lausanne, Switzerland
    For correspondence
    jerome.feige@rd.nestle.com
    Competing interests
    Jerome N Feige, Presently or previously employed by the Société des Produits Nestlé S.A., Switzerland.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-4751-264X
  17. C Florian Bentzinger

    Département de pharmacologie-physiologie, Université de Sherbrooke, Sherbrooke, Canada
    For correspondence
    cf.bentzinger@usherbrooke.ca
    Competing interests
    C Florian Bentzinger, Presently or previously employed by the Société des Produits Nestlé S.A., Switzerland.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-0422-9622

Funding

Canadian Institutes of Health Research (PJT-162442)

  • C Florian Bentzinger

Association Française contre les Myopathies (AFM)

  • Pura Muñoz-Cánoves

MWRF (MWRF)

  • Pura Muñoz-Cánoves

Maria de Maeztu Unit of Excellence award to UPF (MDM-2014-0370)

  • Pura Muñoz-Cánoves

Severo Ochoa Center of Excellence award to the CNIC (SEV-2015-0505)

  • Pura Muñoz-Cánoves

Severo Ochoa FPI predoctoral fellowship (SEV-2015-0505-17-1))

  • Xiaotong Hong

National Science and Research Council of Canada (RGPIN-2017-05490)

  • C Florian Bentzinger

Fonds de Recherche du Québec - Santé (Dossiers 296357,34813,and 36789)

  • C Florian Bentzinger

Centre de Recherche Médicale de l'Université de Sherbrooke (CRMUS Chair)

  • C Florian Bentzinger

European Research Council (ERC-2016-AdG-741966)

  • Pura Muñoz-Cánoves

La Caixa Foundation (La Caixa-HEALTH-HR17-00040)

  • Pura Muñoz-Cánoves

Muscular Dystrophy Association (MDA)

  • Pura Muñoz-Cánoves

H2020 (UPGRADE-H2020-825825)

  • Pura Muñoz-Cánoves

Programa Estatal de Investigacion (RTI2018-096068-B-I00)

  • Pura Muñoz-Cánoves

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Ethics

Animal experimentation: This study was performed in accordance with the Swiss regulation on animal experimentation and the European Community Council directive (86/609/EEC) for the care and use of laboratory animals. Experiments were approved by the Vaud cantonal authorities under license VD3085, and by the Animal Care and Ethics Committee of the Spanish National Cardiovascular Research Center (CNIC) and regional authorities.

Copyright

© 2022, Mashinchian et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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