Preprint Open Access

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; Feige, Jerome N.; Bentzinger, C. Florian


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    <subfield code="a">In Vivo Transcriptomic Profiling using Cell Encapsulation Identifies Effector Pathways of Systemic Aging</subfield>
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    <subfield code="a">&lt;p&gt;&lt;strong&gt;Abstract&lt;/strong&gt;&lt;/p&gt;

&lt;p&gt;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&amp;nbsp;in vivo&amp;nbsp;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,&amp;nbsp;in vitro&amp;nbsp;profiling using young and old serum in 2D culture does not capture all pathways deregulated in encapsulated cells in aged mice. Thus,&amp;nbsp;in vivo&amp;nbsp;transcriptomic profiling using cell encapsulation allows for the characterization of effector pathways of systemic aging with unparalleled accuracy.&lt;/p&gt;

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