Optogenetic control of YAP reveals a dynamic communication code for stem cell fate and proliferation.
Optogenetic control of YAP reveals a dynamic communication code for stem cell fate and proliferation.
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DOI：
10.1038/s41467-023-42643-2
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发表时间：
2023-10-30
影响因子：
16.6
通讯作者：
Weiner, Orion D.
中科院分区：
文献类型：
--
作者：
Meyer, Kirstin;Lammers, Nicholas C.;Bugaj, Lukasz J.;Garcia, Hernan G.;Weiner, Orion D.
YAP is a transcriptional regulator that controls pluripotency, cell fate, and proliferation. How cells ensure the selective activation of YAP effector genes is unknown. This knowledge is essential to rationally control cellular decision-making. Here we leverage optogenetics, live-imaging of transcription, and cell fate analysis to understand and control gene activation and cell behavior. We reveal that cells decode the steady-state concentrations and timing of YAP activation to control proliferation, cell fate, and expression of the pluripotency regulators Oct4 and Nanog. While oscillatory YAP inputs induce Oct4 expression and proliferation optimally at frequencies that mimic native dynamics, cellular differentiation requires persistently low YAP levels. We identify the molecular logic of the Oct4 dynamic decoder, which acts through an adaptive change sensor. Our work reveals how YAP levels and dynamics enable multiplexing of information transmission for the regulation of developmental decision-making and establishes a platform for the rational control of these behaviors. The transcriptional regulator YAP controls cellular decisions such as proliferation, differentiation, and pluripotency. Here, the authors show a concentration-dependent and temporal communication code for YAP that enables cells to choose between these programs.
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