Skeletal muscle is the most abundant tissue in the vertebrate body. Several hundreds of muscles are present in the human body. They are playing an important role not only in the control of movements and posture, but they are also required for respiration, for the control of body temperature, and they exert an important metabolic function. Although muscles appear superficially alike at different anatomical locations, in reality there is considerably more diversity than initially believed. Heterogeneity is apparent during development at the molecular and cellular level. Multiple waves of muscle precursors with different features appear before birth and, by differentiating into syncytial fibers, contribute to muscular diversification.
Importantly, not all the myogenic progenitors terminally differentiate into fibers during development, but a fraction of them remain in the adult muscles as undifferentiated pool of stem cells. These stem cells are mediating muscle repair. Under normal conditions skeletal muscles present a very powerful regenerative response when challenged by injury. Nevertheless, the regenerative potential is progressively lost under specific pathophysiological conditions, such as aging or a variety neuromuscular diseases, in which fibrotic tissue progressively replaces muscle fibers leading to an impairment of muscle function. By employing a combination of in vitro and in vivo approaches, we are exploring the cellular and molecular events responsible for the defective regenerative ability and for the accumulation of fibrotic tissue in diseased muscle in order to set up the basis for effective and highly specific therapeutic approaches.
Using the skeletal muscle system, a tissue that is characterized by a particularly rich presence of stem cells, we are studying the role of key signaling cascades, such as TGFβ, Notch and Wnt pathways in the regulation of the behavior and commitment of stem cells. This research will ultimately contribute to our understanding of the general molecular mechanisms controlling stem cell lineage decisions and will increase our understanding of the pathologies characterized by altered stem cell functionality. See also Dulbecco Telethon Institute Biressi Lab at http://www.telethon.it/node/5729
Mechanisms of fibrosis in muscular dystrophies
Stem cell dysfunction in neuromuscular diseases and aging
Stem cell heterogeneity in muscle development and regeneration
- Stefano Biressi, PI
- Eyemen Kheir, Postdoctoral fellow
- Francesca Florio, PhD student
- Michela Libergoli, PhD student
- Laura Vettori, Undergraduate student
- Thomas Rando, Stanford University, USA
- Giovanni Stefani, Center for Integrative Biology (CIBio), University of Trento, Italy
- Mattia Pelizzola, Istituto Italiano di Tecnologia (iit), Milano, Italy
- Nico Mitro, Universita’ degli Studi di Milano
- Maria Pennuto, Universita’ di Padova
de Morrée A, van Velthoven C, Gan Q, Salvi JS, Klein JD, Akimenko I, Quarta M, Biressi S, and Rando TA. “Staufen1 inhibits MyoD translation to actively maintain muscle stem cell quiescence”. PNAS. 2017; 114(43), E8996-9005.
Biressi S, and Gopinath, SD. The quasi-parallel lives of satellite cells and atrophying muscle. Front. Aging Neurosci. 2015; 7, 140.
Biressi S, Miyabara EH, Gopinath SD, Carlig PMM, Rando TA. “A Wnt-TGFβ2 axis induces a fibrogenic program in muscle stem cells from dystrophic mice”. Sci Transl Med. 2014; 267, 176.
George RM*, Biressi S*, Beres B, Rogers R, Geiger L, Mulia A, Allen ER, Rawls A, Rando TA and Wilson-Rawls J. “Numb deficient satellite cells have a regeneration and proliferation defect”. *These authors equally contributed to this work. PNAS. 2013; 110(46), 18549-54.
Biressi S, Bjornson CRR, Carlig PMM, Nishijo K, Keller C, Rando TA. “Myf5 expression during fetal myogenesis defines the developmental progenitors of adult satellite cells”. Dev Biol. 2013; 379(2), 195-207.
Messina G*, Biressi S*, Monteverde S, Magli A, Cassano M, Perani L, Roncaglia E, Tagliafico E, Starnes L, Cambpell CE, Grossi M, Goldhamer DJ, Gronostajski RM, Cossu G. “Nfix regulates fetal specific transcription in developing skeletal muscle”. *These authors equally contributed to this work. Cell. 2010; 140 (4), 554-66.
Biressi S, Rando TA. “Heterogeneity in the muscle satellite cell population”. Semin Cell Dev Biol. 2010; 21(8), 845-54.
For a complete list: http://www.ncbi.nlm.nih.gov/pubmed/?term=Biressi+S