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 innovative 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 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 regulating the behavior and commitment of stem cells. This research will ultimately contribute to our comprehension of the general molecular mechanisms controlling stem cell lineage decisions and will increase our understanding of the pathologies characterized by their altered functionality.
Intriguingly, understanding the events leading to muscle commitment and differentiation will pave the road to the generation of functional tissue in vitro, which will end up useful not only for the replacement of damaged muscles but also for the production of cell-based meat. Studies aiming at the optimization of cell-based meat production protocols are currently ongoing in our laboratory.
- Stem cell dysfunction in neuromuscular diseases and aging
- Stem cell heterogeneity
- Mechanisms of fibrosis
- Cell and gene therapy of muscle and developmental pathologies
- In vitro modeling of muscle diseases
- Myogenic specification and differentiation
- Generation of myogenic cell lines suitable for cell-based meat production
- Stefano Biressi, PI
- Michela Libergoli, Post-doc
- Francesca Florio, Post-doc
- Giulia Fioravanti, PhD student
- Nike Schiavo, Research Fellow
- Luciano Conti, Department of Cellular Computational and Integrative Biology - CIBIO, University of Trento, Italy
- Giovanni Piccoli, Department of Cellular Computational and Integrative Biology - CIBIO, University of Trento, Italy
- Jessika Bertacchini, University of Modena, Italy
- Yvan Torrente, University of Milan, Italy
- Lorenzo Giordani, Sorbonne Université, Paris, France
- Thomas Rando, Stanford University, California
- Maria Pennuto, University of Padua, Italy
- Paolo Bonaldo, University of Padua, Italy
- Mattia Pelizzola, Italian Institute of Technology (iit), Milan, Italy
- Jean Farup, Aarhus University, Denmark
- Benoit Viollet, Institute Cochin, Paris, France
- Cesare Gargioli, Università Roma Tor Vergata
- Diana Massai, Polytechnic University of Turin, Italy
Cossu G., Tonlorenzi R., Brunelli S., Sampaolesi M., Messina G., Azzoni E., Benedetti S., Biressi S. et al. “Mesoangioblasts at 20: From the embryonic aorta to the patient bed”. Front Genet. 2023: 13:1056114.
Florio F., Accordini S., Libergoli M., Biressi S. “Targeting muscle-resident single cells through in vivo electro-enhanced plasmid transfer in healthy and compromised skeletal muscle”. Front Physiology. 2022: 13:834705.
Magarò MS, Bertacchini J, Florio F, Zavatti M, Potì F, Cavani F, Amore E, De Santis I, Bevilacqua A, Reggiani Bonetti L, Torricelli P, Maurel DB, Biressi S., Palumbo C. “Identification of Sclerostin as a Putative New Myokine Involved in the Muscle-to-Bone Crosstalk”. Biomedicines. 2021: 9(1):E71.
Bauer J., Cuvelier N, Ragab N, Simon-Keller K., Nitzki F., Geyer N., Botermann D.S., Elmer D.P., Rosenberger A., Rando T.A., Biressi S. et al. “Context-dependent modulation of aggressiveness of pediatric tumors by individual oncogenic RAS isoforms.” Oncogene. 2021:40(31):4955-4966.
Biressi S., Filareto A, Rando TA. "Stem cell therapy for muscular dystrophies". J Clin Invest. 2020;130(11):5652-5664.
Kheir E, Cusella G, Messina G, Cossu G, & Biressi S. “Reporter-based Isolation of Developmental Myogenic Progenitors.” Front Physiol. 2018; 5;9:352.
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.
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.