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DENOVOSTEM SIGNED

DE NOVO GENERATION OF SOMATIC STEM CELLS: REGULATION AND MECHANISMS OF CELL PLASTICITY

Total Cost €

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EC-Contrib. €

0

Partnership

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 DENOVOSTEM project word cloud

Explore the words cloud of the DENOVOSTEM project. It provides you a very rough idea of what is the project "DENOVOSTEM" about.

downstream    types    connection    inputs    molecular    culture    establishing    arising    re    physiology    initiation    tissues    de    diseases    artificially    stem    cytoskeletal    inducing    hippo    taz    networks    traits    remodelers    underpinning    mechanics    plasticity    prerequisite    human    ex    epigenetic    differentiated    genetic    cell    regenerative    cellular    identity    possibility    link    biomechanical    basis    induce    pursue    organ    cues    origins    entail    progression    preserve    expand    expression    mediated    transiently    vitro    sc    oncogenes    tumors    regeneration    preliminary    chromatin    somatic    emphasis    terminally    overarching    tissue    appears    primary    regulators    understand    naturally    transformation    reprogramming    immature    vivo    differentiation    gain    cells    yap    sum    scs    grant    tumor    identification    upstream    dish    acquisition    endogenous    oncogene    effectors    nuclear    medicine    found    insights    activation    intriguing    never    modeling   

Project "DENOVOSTEM" data sheet

The following table provides information about the project.

Coordinator
UNIVERSITA DEGLI STUDI DI PADOVA 

Organization address
address: VIA 8 FEBBRAIO 2
city: PADOVA
postcode: 35122
website: www.unipd.it

contact info
title: n.a.
name: n.a.
surname: n.a.
function: n.a.
email: n.a.
telephone: n.a.
fax: n.a.

 Coordinator Country Italy [IT]
 Total cost 2˙498˙934 €
 EC max contribution 2˙498˙934 € (100%)
 Programme 1. H2020-EU.1.1. (EXCELLENT SCIENCE - European Research Council (ERC))
 Code Call ERC-2014-ADG
 Funding Scheme ERC-ADG
 Starting year 2015
 Duration (year-month-day) from 2015-09-01   to  2020-08-31

 Partnership

Take a look of project's partnership.

# participants  country  role  EC contrib. [€] 
1    UNIVERSITA DEGLI STUDI DI PADOVA IT (PADOVA) coordinator 2˙239˙422.00
2    UNIVERSITA DEGLI STUDI DI MODENA E REGGIO EMILIA IT (MODENA) participant 259˙511.00

Map

 Project objective

The possibility to artificially induce and expand in vitro tissue-specific stem cells (SCs) is an important goal for regenerative medicine, to understand organ physiology, for in vitro modeling of human diseases and many other applications. Here we found that this goal can be achieved in the culture dish by transiently inducing expression of YAP or TAZ - nuclear effectors of the Hippo and biomechanical pathways - into primary/terminally differentiated cells of distinct tissue origins. Moreover, YAP/TAZ are essential endogenous factors that preserve ex-vivo naturally arising SCs of distinct tissues. In this grant, we aim to gain insights into YAP/TAZ molecular networks (upstream regulators and downstream targets) involved in somatic SC reprogramming and SC identity. Our studies will entail the identification of the genetic networks and epigenetic changes controlled by YAP/TAZ during cell de-differentiation and the re-acquisition of SC-traits in distinct cell types. We will also investigate upstream inputs establishing YAP/TAZ activity, with particular emphasis on biomechanical and cytoskeletal cues that represent overarching regulators of YAP/TAZ in tissues. For many tumors, it appears that acquisition of an immature, stem-like state is a prerequisite for tumor progression and an early step in oncogene-mediated transformation. YAP/TAZ activation is widespread in human tumors. However, a connection between YAP/TAZ and oncogene-induced cell plasticity has never been investigated. We will also pursue some intriguing preliminary results and investigate how oncogenes and chromatin remodelers may link to cell mechanics, and the plasticity of the differentiated and SC states by controlling YAP/TAZ. In sum, this research should advance our understanding of the cellular and molecular basis underpinning organ growth, tissue regeneration and tumor initiation.

 Publications

year authors and title journal last update
List of publications.
2017 Mattia Forcato, Chiara Nicoletti, Koustav Pal, Carmen Maria Livi, Francesco Ferrari, Silvio Bicciato
Comparison of computational methods for Hi-C data analysis
published pages: 679-685, ISSN: 1548-7091, DOI: 10.1038/nmeth.4325
Nature Methods 14/7 2019-07-05
2016 Francesca Zanconato, Michelangelo Cordenonsi, Stefano Piccolo
YAP/TAZ at the Roots of Cancer
published pages: 783-803, ISSN: 1535-6108, DOI: 10.1016/j.ccell.2016.05.005
Cancer Cell 29/6 2019-07-05
2016 Craig S. Nowell, Pascal D. Odermatt, Luca Azzolin, Sylke Hohnel, Erwin F. Wagner, Georg E. Fantner, Matthias P. Lutolf, Yann Barrandon, Stefano Piccolo, Freddy Radtke
Chronic inflammation imposes aberrant cell fate in regenerating epithelia through mechanotransduction
published pages: 168-180, ISSN: 1465-7392, DOI: 10.1038/ncb3290
Nature Cell Biology 18/2 2019-07-05
2017 Luca Azzolin, Stefano Piccolo
A TIAM Double Hit to Oppose YAP/TAZ
published pages: 607-608, ISSN: 1535-6108, DOI: 10.1016/j.ccell.2017.04.009
Cancer Cell 31/5 2019-07-05
2016 F. Zanconato, S. Piccolo
Eradicating tumor drug resistance at its YAP-biomechanical roots
published pages: 459-461, ISSN: 0261-4189, DOI: 10.15252/embj.201593584
The EMBO Journal 35/5 2019-07-05
2017 Tito Panciera, Luca Azzolin, Michelangelo Cordenonsi, Stefano Piccolo
Mechanobiology of YAP and TAZ in physiology and disease
published pages: 758-770, ISSN: 1471-0072, DOI: 10.1038/nrm.2017.87
Nature Reviews Molecular Cell Biology 18/12 2019-07-05
2017 Tobias Hirsch, Tobias Rothoeft, Norbert Teig, Johann W. Bauer, Graziella Pellegrini, Laura De Rosa, Davide Scaglione, Julia Reichelt, Alfred Klausegger, Daniela Kneisz, Oriana Romano, Alessia Secone Seconetti, Roberta Contin, Elena Enzo, Irena Jurman, Sonia Carulli, Frank Jacobsen, Thomas Luecke, Marcus Lehnhardt, Meike Fischer, Maximilian Kueckelhaus, Daniela Quaglino, Michele Morgante, Silvio Bi
Regeneration of the entire human epidermis using transgenic stem cells
published pages: 327-332, ISSN: 0028-0836, DOI: 10.1038/nature24487
Nature 551/7680 2019-07-04
2016 Tito Panciera, Luca Azzolin, Atsushi Fujimura, Daniele Di Biagio, Chiara Frasson, Silvia Bresolin, Sandra Soligo, Giuseppe Basso, Silvio Bicciato, Antonio Rosato, Michelangelo Cordenonsi, Stefano Piccolo
Induction of Expandable Tissue-Specific Stem/Progenitor Cells through Transient Expression of YAP/TAZ
published pages: 725-737, ISSN: 1934-5909, DOI: 10.1016/j.stem.2016.08.009
Cell Stem Cell 19/6 2019-07-04
2017 Antonio Totaro, Martina Castellan, Giusy Battilana, Francesca Zanconato, Luca Azzolin, Stefano Giulitti, Michelangelo Cordenonsi, Stefano Piccolo
YAP/TAZ link cell mechanics to Notch signalling to control epidermal stem cell fate
published pages: 15206, ISSN: 2041-1723, DOI: 10.1038/ncomms15206
Nature Communications 8 2019-07-05
2018 Shiro Yui, Luca Azzolin, Martti Maimets, Marianne Terndrup Pedersen, Robert P. Fordham, Stine L. Hansen, Hjalte L. Larsen, Jordi Guiu, Mariana R.P. Alves, Carsten F. Rundsten, Jens V. Johansen, Yuan Li, Chris D. Madsen, Tetsuya Nakamura, Mamoru Watanabe, Ole H. Nielsen, Pawel J. Schweiger, Stefano Piccolo, Kim B. Jensen
YAP/TAZ-Dependent Reprogramming of Colonic Epithelium Links ECM Remodeling to Tissue Regeneration
published pages: 35-49.e7, ISSN: 1934-5909, DOI: 10.1016/j.stem.2017.11.001
Cell Stem Cell 22/1 2019-07-04
2016 Francesca Zanconato, Giusy Battilana, Michelangelo Cordenonsi, Stefano Piccolo
YAP/TAZ as therapeutic targets in cancer
published pages: 26-33, ISSN: 1471-4892, DOI: 10.1016/j.coph.2016.05.002
Current Opinion in Pharmacology 29 2019-07-04
2015 Francesca Zanconato, Mattia Forcato, Giusy Battilana, Luca Azzolin, Erika Quaranta, Beatrice Bodega, Antonio Rosato, Silvio Bicciato, Michelangelo Cordenonsi, Stefano Piccolo
Genome-wide association between YAP/TAZ/TEAD and AP-1 at enhancers drives oncogenic growth
published pages: 1218-1227, ISSN: 1465-7392, DOI: 10.1038/ncb3216
Nature Cell Biology 17/9 2019-05-20
2018 Tito Panciera, Luca Azzolin, Daniele Di Biagio, Antonio Totaro, Michelangelo Cordenonsi, Stefano Piccolo
De Novo Generation of Somatic Stem Cells by YAP/TAZ
published pages: , ISSN: 1940-087X, DOI: 10.3791/57462
Journal of Visualized Experiments 135 2019-05-20
2018 Antonio Totaro, Martina Castellan, Daniele Di Biagio, Stefano Piccolo
Crosstalk between YAP/TAZ and Notch Signaling
published pages: 560-573, ISSN: 0962-8924, DOI: 10.1016/j.tcb.2018.03.001
Trends in Cell Biology 28/7 2019-05-20
2017 Giovanni Sorrentino, Naomi Ruggeri, Alessandro Zannini, Eleonora Ingallina, Rebecca Bertolio, Carolina Marotta, Carmelo Neri, Elisa Cappuzzello, Mattia Forcato, Antonio Rosato, Miguel Mano, Silvio Bicciato, Giannino Del Sal
Glucocorticoid receptor signalling activates YAP in breast cancer
published pages: 14073, ISSN: 2041-1723, DOI: 10.1038/ncomms14073
Nature Communications 8 2019-05-20
2018 Francesca Zanconato, Giusy Battilana, Mattia Forcato, Letizia Filippi, Luca Azzolin, Andrea Manfrin, Erika Quaranta, Daniele Di Biagio, Gianluca Sigismondo, Vincenza Guzzardo, Pascale Lejeune, Bernard Haendler, Jeroen Krijgsveld, Matteo Fassan, Silvio Bicciato, Michelangelo Cordenonsi, Stefano Piccolo
Transcriptional addiction in cancer cells is mediated by YAP/TAZ through BRD4
published pages: 1599-1610, ISSN: 1078-8956, DOI: 10.1038/s41591-018-0158-8
Nature Medicine 24/10 2019-05-20
2018 Antonio Totaro, Tito Panciera, Stefano Piccolo
YAP/TAZ upstream signals and downstream responses
published pages: 888-899, ISSN: 1465-7392, DOI: 10.1038/s41556-018-0142-z
Nature Cell Biology 20/8 2019-05-20
2018 Jimmy Caroli, Giovanni Sorrentino, Mattia Forcato, Giannino Del Sal, Silvio Bicciato
GDA, a web-based tool for Genomics and Drugs integrated analysis
published pages: W148-W156, ISSN: 0305-1048, DOI: 10.1093/nar/gky434
Nucleic Acids Research 46/W1 2019-05-20

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