Department of Physiology, Howard Hughes Medical Institute, University of Texas Southwestern Medical Center, Dallas, TX, USA.
Nat Rev Mol Cell Biol. 2023 Dec;24(12):895-911. doi: 10.1038/s41580-023-00644-5. Epub 2023 Aug 25.
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.
复杂的生理过程控制着干细胞是自我更新、分化还是静止。二十年来的研究将 Hippo 通路（一种高度保守的激酶信号级联反应）及其下游分子效应物 YAP 和 TAZ 置于这一决策的核心位置。YAP 和 TAZ 将作用于干细胞的复杂生物学信号（从机械力到细胞代谢）转化为全基因组效应，从而介导干细胞功能。虽然异常的 YAP/TAZ 活性会导致衰老、肿瘤发生和疾病中的干细胞功能障碍，但 Hippo 信号和 YAP/TAZ 的治疗靶向可以增强干细胞活性，从而促进再生。在这篇综述中，我们讨论了 YAP/TAZ 如何在不同的情况下控制干细胞的自我更新、命运和可塑性，YAP/TAZ 在干细胞中的失调如何导致疾病，以及靶向 YAP/TAZ 的治疗方式如何有益于再生医学和癌症治疗。
