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  • Review Article
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Control of stem cell renewal and fate by YAP and TAZ

Abstract

Complex physiological processes control whether stem cells self-renew, differentiate or remain quiescent. Two decades of research have placed the Hippo pathway, a highly conserved kinase signalling cascade, and its downstream molecular effectors YAP and TAZ at the nexus of this decision. YAP and TAZ translate complex biological cues acting on stem cells — from mechanical forces to cellular metabolism — into genome-wide effects to mediate stem cell functions. While aberrant YAP/TAZ activity drives stem cell dysfunction in ageing, tumorigenesis and disease, therapeutic targeting of Hippo signalling and YAP/TAZ can boost stem cell activity to enhance regeneration. In this Review, we discuss how YAP/TAZ control the self-renewal, fate and plasticity of stem cells in different contexts, how dysregulation of YAP/TAZ in stem cells leads to disease, and how therapeutic modalities targeting YAP/TAZ may benefit regenerative medicine and cancer therapy.

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Fig. 1: Stem cell-specific functions of YAP/TAZ.
Fig. 2: YAP/TAZ in early mammalian (mouse) embryogenesis.
Fig. 3: The role of YAP/TAZ in stem cell renewal and differentiation during development.
Fig. 4: The role of YAP/TAZ in stem cells in mature tissues.
Fig. 5: Strategies to modulate YAP/TAZ in cancer and regeneration.

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Acknowledgements

We apologize to our colleagues whose work we could not discuss and cite due to space and size limitations. Research in the Pan laboratory is supported in part by grants from the National Institutes of Health (EY015708) and Department of Defense (PR190360). D.P. is an investigator at the Howard Hughes Medical Institute.

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Driskill, J.H., Pan, D. Control of stem cell renewal and fate by YAP and TAZ. Nat Rev Mol Cell Biol 24, 895–911 (2023). https://doi.org/10.1038/s41580-023-00644-5

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