研究动态
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YAP和TAZ对干细胞更新和命运的调控。

Control of stem cell renewal and fate by YAP and TAZ.

发表日期:2023 Aug 25
作者: Jordan H Driskill, Duojia Pan
来源: Stem Cell Research & Therapy

摘要:

复杂的生理过程控制着干细胞是自我更新、分化还是保持静止。两十年的研究将高度保守的Hippo通路,一种高度保守的激酶信号级联,以及它的下游分子效应器YAP和TAZ放置在这个决定的纽带上。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——翻译成全基因组效应,以介导干细胞功能。虽然异常的YAP/TAZ活性在衰老、肿瘤发生和疾病中会驱动干细胞功能紊乱,但通过治疗性靶向Hippo信号和YAP/TAZ可以增强干细胞活性以增强再生。在本综述中,我们讨论了YAP/TAZ在不同环境中如何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,以及如何通过靶向YAP/TAZ的治疗方式可能有益于再生医学和癌症治疗。© 2023. Springer Nature Limited.
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.© 2023. Springer Nature Limited.