Du muscle en développement au muscle vieillissant

Wednesday, March 27, 2019
27-PM-Parallel-2 4:30 PM > 6:00 PM Du muscle en développement au muscle vieillissant Amphi A

4:30 PM S14-01 Regulation of the mouse skeletal muscle stem cell niche during homeostasis and regeneration > S. Shahragim TAJBAKHSH
Objectives : Regulation of skeletal muscle stem cells during homeostasis and regeneration involves the interplay between extrinsic and intrinsic cues. In a series of studies, we investigated Notch as a key mediator of muscle stem cell stability and fate through extrinsic regulation of extracellular matrix, and internal regulation of cell migration via the mirtron mir708. Using static and live imaging, these observations led us to propose a two-step mechanism where the final mitosis before cellular quiescence, and cell migration, are negotiated before niche occupancy. Using cell lineage reporter mice, our data show that muscle stem cells exit from the cell cycle first, continue to migrate, then arrest and occupy the niche under the regulation of two Notch mediated axes. In parallel, we developed a novel in vivo clonal cell lineage method using Pax7 reporter mice to mark all muscle stem cells, and combined this with transcription factor readouts (Pax7, MyoD and Myogenin as stem and differentiating markers) to assess division asymmetry. Our ex vivo live imaging of artificial niches on fibronectin coated micropatterns, and in vivo clonal analyses show for the first time that asymmetric and symmetric cell divisions both contribute to the self-renewal process in vivo. This division asymmetry was examined in more detail using H3.1-SNAP transgenic mice that we generated that allow tracking of old and new histone pools. Using this transgenic in combination with clonal lineage studies in vivo, we show that in contrast to the fly germ line where this histone variant was reported to segregate asymmetrically, we observe symmetric distribution of H3.1 during muscle stem cell asymmetric cell divisions. Taken together, we show that muscle stem cell regulation is dynamic during homeostasis and regeneration and we propose a model of how the asymmetry apparatus engages in cell fate decisions during muscle stem cell self-renewal and differentiation during tissue regeneration.
5:00 PM S14-02 Recovery macrophages secrete pro-fusogenic effectors during skeletal muscle regeneration > B. Bénédicte CHAZAUD 5:30 PM S14-03 Dynamics of muscle growth, regeneration and hypertrophy provide an essential quantitative basis to understanding muscle stem cell function > T. Terence PARTRIDGE 5:45 PM S14-04 Attenuation of myostatin/activin signaling delay aging signs in progeric mice model > K. Khalid ALYODAWI

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