Aragona Group - Tissue Architecture

Mechanisms regulating the response to stretching in the skin

The capacity of the skin to expand as a reaction to stretching is a property commonly exploited in plastic surgery to generate an excess of skin that can be used to repair birth defects, scars, and for breast reconstruction after mastectomy. We developed a mouse model in which the temporal consequences of stretching the skin can be studied in vivo. We are investigating how different cell types in the skin respond to stretching and how they coordinate their behaviors.

Principles of cellular urinary tract homeostasis

Fluid flow and hydrostatic pressure play substantial roles during morphogenesis and homeostasis. We are studying the epithelium of the urinary tract that is under frequent mechanical loading and unloading due to the urine flow, providing a model in which we can interrogate the effect of fluid mechanics on epithelia biology.

Mechanotransduction in the bladder urothelium

Urination is a physiological process that involved cycles of stretching and contraction of the bladder allowing the elimination of waste from the body. The urothelium, that lines the bladder wall, is able to detect the mechanical changes that are associated with filling and voiding, and to transmit them to neighbouring tissues to regulate bladder functions. We are defining the factors able to read the tensional status of the urothelium (molecular mechanosensors ) and the factors able to translate and communicate ( mechanotransducers ) the physical changes of the urothelium to deeper tissue compartments.

• Nguyen TM & Aragona M. Regulation of tissue architecture and stem cell dynamics to sustain homeostasis and repair in the skin epidermis. Semin Cell Dev Biol. 2021 Sept 23. doi: 10.1016/j.semcdb.2021.09.008.
• Aragona M, Sifrim A, Malfait M, Song Y, Van Herck J, Dekoninck S, Gargouri S, Lapouge G, Swedlund B, Dubois C, Baatsen P, Vints K, Han S, Tissir F, Voet T, Simons BD, Blanpain C. Mechanisms of stretch-mediated skin expansion at single cell resolution. Nature. 2020 Jul 29. doi: 10.1038/s41586-020-2555-7.
• Aragona M#, Dekoninck S#, Rulands S, Lenglez S, Mascré G, Simons BD, Blanpain C. Defining stem cell dynamics and migration during wound healing in mouse skin epidermis. Nat Commun. 2017 Mar 1;8:14684. doi: 10.1038/ncomms14684.
• Aragona M, Panciera T, Manfrin A, Giulitti S, Michielin F, Elvassore N, Dupont S, Piccolo S. A mechanical checkpoint controls multicellular growth through YAP/TAZ regulation by actin- processing factors. Cell. 2013 Aug 29;154(5):1047-1059. doi: 10.1016/j.cell.2013.07.042.
• Dupont S#, Morsut L#, Aragona M, Enzo E, Giulitti S, Cordenonsi M, Zanconato F, Le Digabel J, Forcato M, Bicciato S, Elvassore N, Piccolo S. Role of YAP/TAZ in mechanotransduction. Nature. 2011 Jun 8;474(7350):179-83. doi: 10.1038/nature10137.

List of publications by Mariaceleste Aragona

• Professor Magdalena Fossum, MD, PhD, Department of Surgical Gastroenterology, Centre for Cancer and Organ Diseases, Rigshospitalet, University of Copenhagen.

• Assistant Professor Alejandro Sifrim, PhD, Department of Human Genetics, KU Leuven, Belgium.

• Professor Sirio Dupont, PhD, University of Padova, Italy.

• Assistant Professor Elena Enzo, PhD, Centre for Regenerative Medicine, University of Modena and Reggio Emilia, Italy.

• Assistant Professor Maria Antfolk, PhD, Department of Biomedical Engineering, Lund University, Sweden.

• NNF Project Grants in Bioscience and Basic Biomedicine for the project “Defining the cellular and molecular mechanisms regulating the homeostasis of the urethral epithelium”.
• Danmarks Frie Forskningsfond (DFF) Research Project grant for the project “Tracing the fibroblast response to stretch-mediated tissue expansion”.
• Leo Foundation Research grant for the project “Unravel fibroblast-epithelial crosstalk supporting keratinocytes self-renewal to improve skin graft production”.
• Marie-Curies Fellowship to Michael Magnussen for the project  ”Chip URInary Engineered System for modelling bladder biomechanics and disease (CURIES)”.

• Animal models: transgenic mouse models, lineage tracing, fate mapping, clonal analysis

• Histology: whole mounts, immunohistochemistry

• Microscopy: confocal fluorescence microcopy, light-sheet microscopy, in vitro cell live imaging,

• Organoids:  adult tissue-specific epithelial stem cells isolation, expansion, and differentiation in vitro, 3D cultures

• Genomics: single-cell-RNA-sequencing, ATAC-seq, spatial transcriptomic, gene regulatory network analysis