ERK1/2作为一个中心枢纽，通过多方面的调控网络保护启动的人类胚胎干细胞的身份
ERK1/2 function as a central hub safeguarding primed human embryonic stem cell identity via multifaceted regulatory networks.
摘要(中文译文)
ERK1/2在多种细胞过程中发挥关键作用，但其在人胚胎干细胞（hESCs）中的功能及潜在机制仍未完全阐明。本研究构建了具有梯度ERK1/2活性的hESC系，并证明适度的ERK1/2激活——同时保持完整的激酶活性和核定位能力——是维持始发态多能性（primed pluripotency）的最佳状态。具体而言，ERK1/2过度激活诱导中内胚层分化，而其缺失则驱动滋养层样分化。在机制上，ERK1/2主要通过直接调控关键转录因子（如MYC、ZIC2和FOS）以及与Hippo和BMP信号通路交互作用来调控多能性。此外，ERK1/2维持MYC-Ac-CoA-H3K27ac轴的稳态并约束CDK1-EZH2-H3K27me3轴，从而激活多能性基因并抑制滋养层谱系基因。总之，本研究系统解析了ERK1/2在hESCs中的直接和间接调控功能，揭示了一个以ERK1/2为中心枢纽的整体调控网络，用以调控始发态hESCs的多能性。
Abstract
ERK1/2 play crucial roles in diverse cellular processes, yet their functions and underlying mechanisms in human embryonic stem cells (hESCs) remain incompletely defined. Here, we generate hESC lines with graded ERK1/2 activities and demonstrate that moderate ERK1/2 activation, with intact kinase activity and nuclear localization capacity, is optimal for sustaining the primed pluripotency state. Specifically, ERK1/2 hyperactivation induces mesendoderm differentiation, whereas their depletion drives trophoblast-like differentiation. Mechanistically, ERK1/2 govern pluripotency primarily through directly controlling key transcription factors (e.g., MYC, ZIC2, and FOS) and crosstalking with Hippo and BMP signaling pathways. Additionally, ERK1/2 preserve the homeostasis of the MYC-Ac-CoA-H3K27ac axis and constrain the CDK1-EZH2-H3K27me3 axis, thereby activating pluripotency genes and repressing trophoblast lineage genes. Collectively, this study systematically deciphers direct and indirect regulatory functions of ERK1/2 in hESCs, revealing a holistic regulatory network, in which ERK1/2 act as a central hub, to govern pluripotency of primed hESCs.
如何引用
AMA
Yifan Zhou, Hanzhi Zhao, Min Shao, Weixuan Lu, Huiyuan Jiao, Lingjie Li, et al. ERK1/2 function as a central hub safeguarding primed human embryonic stem cell identity via multifaceted regulatory networks.. Cell reports. 2026; doi:10.1016/j.celrep.2026.117675.
APA
Yifan Zhou, Hanzhi Zhao, Min Shao, Weixuan Lu, Huiyuan Jiao, Lingjie Li, et al (2026). ERK1/2 function as a central hub safeguarding primed human embryonic stem cell identity via multifaceted regulatory networks.. Cell reports. https://doi.org/10.1016/j.celrep.2026.117675
GB/T 7714
Yifan Zhou, Hanzhi Zhao, Min Shao, Weixuan Lu, Huiyuan Jiao, Lingjie Li, et al. ERK1/2 function as a central hub safeguarding primed human embryonic stem cell identity via multifaceted regulatory networks.[J]. Cell reports, 2026 doi:10.1016/j.celrep.2026.117675.
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