cfaed Seminar Series

Prof. Gianni Cesareni , University of Rome Tor Vergata

Why fat does not accumulate in the muscle of a healthy vertebrate? A systems biology approach

20.01.2017 (Friday) , 11:00 - 12:00
MPI-CBG, Auditorium , Pfotenhauerstraße 108 , Dresden

Muscle regeneration is governed by a complex crosstalk among dozen and more cell
types. Fibro-adipogenic precursors (FAPS) play an important role in this process by
positively regulating the activation and maturation of satellite cells, the muscle progenitor
cells. FAPs, however, when cultured i/n vitro/, show a remarkable capacity to differentiate
into adipocytes and fibroblasts. FAPs, indeed, are held responsible for the deposition of fat
and fibrotic infiltrates in the degenerating muscles of dystrophic or old individuals. Fat
depositions, however, are not observed in the interstitial regions between the fibers of
healthy muscles of young individuals.
We have modeled by a system of differential equation the process of muscle regeneration.
The model takes into account the complex network of interactions between the different
mononuclear cells that are resident in the muscle or are attracted to the muscle following
damage or chronic strain. This model faithfully represents the activation kinetic of the
different muscle cell types but predicts the accumulation of adipocytes, which is not
observed in physiological conditions. By purifying the different muscle cell types and by
testing them in pairwise combinations we have shown that myotubes negatively control
FAP differentiation by activating the NOTCH pathway. Remarkably adipogenesis of FAPs
from a murine dystrophy model cannot be controlled by the NOTCH ligand, providing a
rational basis for the observation that dystrophic patients, with age, accumulate fat and
scars in the muscle tissue. I will provide evidence of the molecular basis in this defect in
differentiation control.

Gianni Cesareni is a Full Professor of Genetics at the University of Rome Tor
Vergata (Italy). After obtaining a degree in physics at the University of Rome La
Sapienza he spent three years in Cambridge in the laboratory of Sidney
Brenner. He then moved to the EMBL in Heidelberg where for nine years he led
a group working on the mechanisms controlling plasmid DNA replication. Since
1989 he teaches and works in Rome. He has been interested in the interplay
between specificity and promiscuity in the protein interaction network mediated
by protein recognition modules. Over the past couple of years a large fraction of
the group has focused on a project aimed at understanding the process of
muscle regeneration from a systems perspective. He is a member of the
European Molecular Biology Organization. He is a recipient of an ERC
advanced grant.

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