title: Induction of Expandable Tissue-Specific Stem/Progenitor Cells through Transient Expression of YAP/TAZ.
abstract: 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.
authors.affiliation: Department of Molecular Medicine, University of Padua School of Medicine, viale Colombo 3, 35126 Padua, Italy.
authors.forename: Tito
authors.initials: T
authors.lastname: Panciera
authors.affiliation: Department of Molecular Medicine, University of Padua School of Medicine, viale Colombo 3, 35126 Padua, Italy.
authors.forename: Luca
authors.initials: L
authors.lastname: Azzolin
authors.affiliation: Department of Molecular Medicine, University of Padua School of Medicine, viale Colombo 3, 35126 Padua, Italy.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Fujimura
authors.affiliation: Department of Molecular Medicine, University of Padua School of Medicine, viale Colombo 3, 35126 Padua, Italy.
authors.forename: Daniele
authors.initials: D
authors.lastname: Di Biagio
authors.affiliation: Department of Woman and Child Health, Haemato-Oncology Laboratory, University of Padua, via Giustiniani 3, 35128 Padua, Italy.
authors.forename: Chiara
authors.initials: C
authors.lastname: Frasson
authors.affiliation: Department of Woman and Child Health, Haemato-Oncology Laboratory, University of Padua, via Giustiniani 3, 35128 Padua, Italy.
authors.forename: Silvia
authors.initials: S
authors.lastname: Bresolin
authors.affiliation: Department of Molecular Medicine, University of Padua School of Medicine, viale Colombo 3, 35126 Padua, Italy.
authors.forename: Sandra
authors.initials: S
authors.lastname: Soligo
authors.affiliation: Department of Woman and Child Health, Haemato-Oncology Laboratory, University of Padua, via Giustiniani 3, 35128 Padua, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Basso
authors.affiliation: Center for Genome Research, Department of Life Sciences, University of Modena and Reggio Emilia, via G. Campi 287, 41100 Modena, Italy.
authors.forename: Silvio
authors.initials: S
authors.lastname: Bicciato
authors.affiliation: Istituto Oncologico Veneto IOV-IRCCS and Department of Surgery, Oncology, and Gastroenterology, University of Padua School of Medicine, via Gattamelata 64, 35128 Padua, Italy.
authors.forename: Antonio
authors.initials: A
authors.lastname: Rosato
authors.affiliation: Department of Molecular Medicine, University of Padua School of Medicine, viale Colombo 3, 35126 Padua, Italy.
authors.forename: Michelangelo
authors.initials: M
authors.lastname: Cordenonsi
authors.affiliation: Department of Molecular Medicine, University of Padua School of Medicine, viale Colombo 3, 35126 Padua, Italy. Electronic address: piccolo@bio.unipd.it.
authors.forename: Stefano
authors.initials: S
authors.lastname: Piccolo
mesh_terms: D061354:Acinar Cells / Q000166:cytology / Q000378:metabolism; D000217:Acyltransferases; D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism*; D000818:Animals; D018797:Cell Cycle Proteins; D002454:Cell Differentiation; D019070:Cell Lineage; D049109:Cell Proliferation; D005260:Female; D008321:Mammary Glands, Animal / Q000166:cytology*; D008810:Mice, Inbred C57BL; D058953:Neural Stem Cells / Q000166:cytology / Q000378:metabolism; D009474:Neurons / Q000166:cytology; D009928:Organ Specificity; D009940:Organoids / Q000166:cytology; D046790:Pancreas, Exocrine / Q000166:cytology; D010750:Phosphoproteins / Q000378:metabolism*; D012038:Regeneration; D015203:Reproducibility of Results; D013234:Stem Cells / Q000378:metabolism*; D014157:Transcription Factors / Q000378:metabolism*; D000091102:YAP-Signaling Proteins
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D018797:Cell Cycle Proteins; D010750:Phosphoproteins; D014157:Transcription Factors; D000091102:YAP-Signaling Proteins; C486223:Yap1 protein, mouse; D000217:Acyltransferases; C486363:tafazzin protein, mouse