Abstract
SummaryThe 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.
Highlights
Stem cells (SCs) display the capacity to self-renew when they divide and to generate a differentiated progeny
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
Because YAP/TAZ function is 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
Summary
Reprogramming and lineage conversions have highlighted the plasticity of differentiated cell states. 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. Highlights d YAP/TAZ expression turns differentiated mammary gland cells into mammary stem cells. 2016, Cell Stem Cell 19, 725–737 December 1, 2016 a 2016 The Authors.
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