In vivo transcriptomic profiling using cell encapsulation identifies effector pathways of systemic aging

Mashinchian, Omid; Hong, Xiaotong; Michaud, Joris; Migliavacca, Eugenia; Lefebvre, Gregory; Boss, Christophe; De Franceschi, Filippo; Le Moal, Emmeran; Collerette-Tremblay, Jasmin; Isern, Joan; Metairon, Sylviane; Raymond, Frederic; Descombes, Patrick; Bouche, Nicolas; Muñoz Cánoves, Pura, 1962-; Feige, Jerome N.; Bentzinger, C. Florian

In vivo transcriptomic profiling using cell encapsulation identifies effector pathways of systemic aging

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dc.contributor.author Mashinchian, Omid
dc.contributor.author Hong, Xiaotong
dc.contributor.author Michaud, Joris
dc.contributor.author Migliavacca, Eugenia
dc.contributor.author Lefebvre, Gregory
dc.contributor.author Boss, Christophe
dc.contributor.author De Franceschi, Filippo
dc.contributor.author Le Moal, Emmeran
dc.contributor.author Collerette-Tremblay, Jasmin
dc.contributor.author Isern, Joan
dc.contributor.author Metairon, Sylviane
dc.contributor.author Raymond, Frederic
dc.contributor.author Descombes, Patrick
dc.contributor.author Bouche, Nicolas
dc.contributor.author Muñoz Cánoves, Pura, 1962-
dc.contributor.author Feige, Jerome N.
dc.contributor.author Bentzinger, C. Florian
dc.date.accessioned 2022-06-13T06:11:03Z
dc.date.available 2022-06-13T06:11:03Z
dc.date.issued 2022
dc.description.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.
dc.description.sponsorship We thank Phoukham Phothirath and Oliver Rizzo of the preclinical investigations group of Nestlé Research for expert advice and support with in vivo experiments. OM, JNF, and CFB are supported by the Fondation Suisse de Recherche sur les Maladies Musculaires (FSRMM). CFB is supported by the Canadian Institutes of Health Research (CIHR, PJT-162442), the Natural Sciences and Engineering Research Council of Canada (NSERC, RGPIN-2017-05490), the Fonds de Recherche du Québec – Santé (FRQS, Dossiers 296357, 34813, and 36789), the ThéCell Network (supported by the FRQS), the Canadian Stem Cell Network, and a research chair of the Centre de Recherche Médicale de l’Université de Sherbrooke (CRMUS). PMC is supported by ERC-2016-AdG-741966, La Caixa-HEALTH-HR17-00040, MDA, AFM, MWRF, UPGRADE-H2020-825825, RTI2018-096068-B-I00, a María de Maeztu Unit of Excellence award to UPF (MDM-2014-0370), and a Severo Ochoa Center of Excellence award to the CNIC (SEV-2015-0505). XH is recipient of a Severo Ochoa FPI (SEV-2015-0505-17-1) predoctoral fellowship.
dc.format.mimetype application/pdf
dc.identifier.citation Mashinchian O, Hong X, Michaud J, Migliavacca E, Lefebvre G, Boss C, De Franceschi F, Le Moal E, Collerette-Tremblay J, Isern J, Metairon S, Raymond F, Descombes P, Bouche N, Muñoz-Cánoves P, Feige JN, Bentzinger CF. In vivo transcriptomic profiling using cell encapsulation identifies effector pathways of systemic aging. Elife. 2022 Mar 4;11:e57393. DOI: 10.7554/eLife.57393
dc.identifier.doi http://dx.doi.org/10.7554/eLife.57393
dc.identifier.issn 2050-084X
dc.identifier.uri http://hdl.handle.net/10230/53462
dc.language.iso eng
dc.publisher eLife
dc.relation.ispartof Elife. 2022 Mar 4;11:e57393
dc.relation.projectID info:eu-repo/grantAgreement/EC/H2020/825825
dc.relation.projectID info:eu-repo/grantAgreement/ES/2PE/RTI2018-096068-B-I00
dc.rights © 2022, Mashinchian et al. This article is distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use and redistribution provided that the original author and source are credited.
dc.rights.accessRights info:eu-repo/semantics/openAccess
dc.rights.uri http://creativecommons.org/licenses/by/4.0/
dc.subject.keyword MuSCs
dc.subject.keyword Aging
dc.subject.keyword Cell biology
dc.subject.keyword Cell encapsulation
dc.subject.keyword Mouse
dc.subject.keyword Myogenic progenitors
dc.subject.keyword Satellite cells
dc.subject.keyword Skeletal muscle
dc.subject.keyword Transcriptomics
dc.title In vivo transcriptomic profiling using cell encapsulation identifies effector pathways of systemic aging
dc.type info:eu-repo/semantics/article
dc.type.version info:eu-repo/semantics/publishedVersion

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