In vivo transcriptomic profiling using cell encapsulation identifies effector pathways of systemic aging
- Nestlé Research, Switzerland
- Université de Sherbrooke, Canada
- Centro Nacional de Investigaciones Cardiovasculares, Spain
- 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.
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In Vivo Transcriptomic Profiling using Cell Encapsulation Identifies Effector Pathways of Systemic AgingNCBI Gene Expression Omnibus, GSE111401.
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In Vivo Transcriptomic Profiling using Cell Encapsulation Identifies Effector Pathways of Systemic AgingNCBI Gene Expression Omnibus, GSE193665.
Article and author information
Author details
C Florian Bentzinger
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.
Reviewing Editor
- Veronica Galvan, UT Health San Antonio, United States
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.
Version history
- Preprint posted: March 9, 2020 (view preprint)
- Received: March 30, 2020
- Accepted: February 28, 2022
- Accepted Manuscript published: March 4, 2022 (version 1)
- Accepted Manuscript updated: March 7, 2022 (version 2)
- Version of Record published: March 16, 2022 (version 3)
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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In vivo transcriptomic profiling using cell encapsulation identifies effector pathways of systemic aging
eLife 11:e57393.
https://doi.org/10.7554/eLife.57393
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