Induction of Expandable Tissue-Specific Stem/Progenitor Cells through Transient Expression of YAP/TAZ

• Published in: Cell stem cell 2016-12, Vol.19 (6), p.725-737
• Main Authors: Panciera, Tito, Azzolin, Luca, Fujimura, Atsushi, Di Biagio, Daniele, Frasson, Chiara, Bresolin, Silvia, Soligo, Sandra, Basso, Giuseppe, Bicciato, Silvio, Rosato, Antonio, Cordenonsi, Michelangelo, Piccolo, Stefano
• Format: Article
• Language: English
• Subjects: Acinar Cells - cytology; Acinar Cells - metabolism; Acyltransferases; Adaptor Proteins, Signal Transducing - metabolism; Animals; Cell Cycle Proteins; Cell Differentiation; Cell Lineage; Cell Proliferation; Female; Mammary Glands, Animal - cytology; Mice, Inbred C57BL; Neural Stem Cells - cytology; Neural Stem Cells - metabolism; Neurons - cytology; Organ Specificity; Organoids - cytology; Pancreas, Exocrine - cytology; Phosphoproteins - metabolism; Regeneration; Reproducibility of Results; Stem Cells - metabolism; Transcription Factors - metabolism; YAP-Signaling Proteins
• ISSN: 1934-5909; 1875-9777
• DOI: 10.1016/j.stem.2016.08.009

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. [Display omitted] •YAP/TAZ expression turns differentiated mammary gland cells into mammary stem cells•YAP-induced MaSCs form organoids and have reconstitution capacity•Induction of YAP in differentiated fetal neurons yields tripotent neural stem cells•Pancreatic exocrine cells are also converted to progenitors by YAP expression Reprogramming and lineage conversions have highlighted the plasticity of differentiated cell states. Here Panciera et al. build on these principles by showing that expression of YAP/TAZ can convert a range of differentiated cells into somatic stem cells of the same tissue, respecting lineage restrictions.