TY - JOUR
T1 - Induction of Expandable Tissue-Specific Stem/Progenitor Cells through Transient Expression of YAP/TAZ
AU - Panciera, Tito
AU - Azzolin, Luca
AU - Fujimura, Atsushi
AU - Di Biagio, Daniele
AU - Frasson, Chiara
AU - Bresolin, Silvia
AU - Soligo, Sandra
AU - Basso, Giuseppe
AU - Bicciato, Silvio
AU - Rosato, Antonio
AU - Cordenonsi, Michelangelo
AU - Piccolo, Stefano
N1 - Funding Information:
We thank O. Wessely, G. Martello, S. Dupont, and F. Zanconato for comments; V. Guzzardo for histology; C. Mucignat for advice on brain stainings; A. Migliorati, P. Raffa, and V. Di Iorio for help with live cell imaging; D.J. Pan, F. Camargo, C. Blanpain, G. Carmignoto, P. Chambon, D. Merkler, I. De Curtis, and R. Brambilla for gifts of mice; and L. Naldini for plasmids. We are indebted to P.G. Pellici and A. Santoro for advice on mammary fat pad transplantation, M. Forcato for help with bioinformatic analyses, and V. Broccoli and A. Sessa for advice on NSC transplantation. R26-rtTA, R26-LSL-rtTA-IRES-EGFP, and Ptf1a-CreERTM mice were purchased from The Jackson Laboratory, where they were deposited by R. Jaenisch, A. Nagy, and C. Wright, respectively. L.A. is supported by a fellowship from the Italian Association for Cancer Research (AIRC). A.F. is the recipient of an Astellas Foundation for Research on Metabolic Disorders fellowship and Japan Society for the Promotion of Science fellowship. This work is supported by a Fondazione Città della Speranza grant and CARIPARO Bando Ricerca Pediatrica (to G.B.), by AIRC Special Program Molecular Clinical Oncology “5 per mille” and an AIRC PI grant (to S.P.), and by Epigenetics Flagship project CNR-Miur grants (to S.P.). This project has received funding from the European Research Council (ERC) under the European Union’s Horizon 2020 Research and Innovation Program (Grant Agreement No. 670126-DENOVOSTEM).
Publisher Copyright:
© 2016 The Authors
PY - 2016/12/1
Y1 - 2016/12/1
N2 - The ability to induce autologous tissue-specific stem cells in culture could have a variety of applications in regenerative medicine and disease modeling. Here we show that transient expression of exogenous YAP or its closely related paralogue TAZ in primary differentiated mouse cells can induce conversion to a tissue-specific stem/progenitor cell state. Differentiated mammary gland, neuronal, and pancreatic exocrine cells, identified using a combination of cell sorting and lineage tracing approaches, efficiently convert to proliferating cells with properties of stem/progenitor cells of their respective tissues after YAP induction. YAP-induced mammary stem/progenitor cells show molecular and functional properties similar to endogenous MaSCs, including organoid formation and mammary gland reconstitution after transplantation. Because YAP/TAZ function is also important for self-renewal of endogenous stem cells in culture, our findings have implications for understanding the molecular determinants of the somatic stem cell state.
AB - The ability to induce autologous tissue-specific stem cells in culture could have a variety of applications in regenerative medicine and disease modeling. Here we show that transient expression of exogenous YAP or its closely related paralogue TAZ in primary differentiated mouse cells can induce conversion to a tissue-specific stem/progenitor cell state. Differentiated mammary gland, neuronal, and pancreatic exocrine cells, identified using a combination of cell sorting and lineage tracing approaches, efficiently convert to proliferating cells with properties of stem/progenitor cells of their respective tissues after YAP induction. YAP-induced mammary stem/progenitor cells show molecular and functional properties similar to endogenous MaSCs, including organoid formation and mammary gland reconstitution after transplantation. Because YAP/TAZ function is also important for self-renewal of endogenous stem cells in culture, our findings have implications for understanding the molecular determinants of the somatic stem cell state.
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U2 - 10.1016/j.stem.2016.08.009
DO - 10.1016/j.stem.2016.08.009
M3 - Article
C2 - 27641305
AN - SCOPUS:84994728929
SN - 1934-5909
VL - 19
SP - 725
EP - 737
JO - Cell stem cell
JF - Cell stem cell
IS - 6
ER -