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

• DOI: 10.1016/j.stem.2016.08.009
• Publication Date: 2016-09-16T03:31:56Z
• Authors: Tito Panciera; Luca Azzolin; Atsushi Fujimura; Daniele Di Biagio; Chiara Frasson; Silvia Bresolin; Sandra Soligo; Giuseppe Basso; Silvio Bicciato; Antonio Rosato; Michelangelo Cord...; Stefano Piccolo
• Keywords: Cell Cycle Proteins; Acinar Cells; Article; 03 medical and health sciences; Mammary Glands, Animal; Neural Stem Cells; Genetics; Animals; Regeneration; Cell Lineage; Molecular Medicine; Genetics; Cell Biology; Adaptor Proteins, Signal Transducing; Cell Proliferation; Neurons; 0303 health sciences; Stem Cells; Reproducibility of Results; Cell Differentiation; Cell Biology; Phosphoproteins; Pancreas, Exocrine; Mice, Inbred C57BL; Organoids; Organ Specificity; Molecular Medicine; Female; Acyltransferases

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.