生物
细胞生物学
STAT1
神经干细胞
干细胞
信号转导
细胞信号
细胞外
促炎细胞因子
免疫系统
免疫学
炎症
作者
Chiara Cossetti,Nunzio Iraci,Tim R. Mercer,Tommaso Leonardi,Emanuele Alpi,Denise Drago,Clara Alfaro-Cervelló,Harpreet K. Saini,Matthew P Davis,Julia Schaeffer,Beatriz Rodríguez Vega,Matilde Stefanini,Chenyang Zhao,Werner Müller,José Manuel García‐Verdugo,Suresh Mathivanan,Ángela Bachi,Anton J. Enright,John S. Mattick,Stefano Pluchino
出处
期刊:Molecular Cell
[Elsevier]
日期:2014-10-01
卷期号:56 (2): 193-204
被引量:254
标识
DOI:10.1016/j.molcel.2014.08.020
摘要
The idea that stem cell therapies work only via cell replacement is challenged by the observation of consistent intercellular molecule exchange between the graft and the host. Here we defined a mechanism of cellular signaling by which neural stem/precursor cells (NPCs) communicate with the microenvironment via extracellular vesicles (EVs), and we elucidated its molecular signature and function. We observed cytokine-regulated pathways that sort proteins and mRNAs into EVs. We described induction of interferon gamma (IFN-γ) pathway in NPCs exposed to proinflammatory cytokines that is mirrored in EVs. We showed that IFN-γ bound to EVs through Ifngr1 activates Stat1 in target cells. Finally, we demonstrated that endogenous Stat1 and Ifngr1 in target cells are indispensable to sustain the activation of Stat1 signaling by EV-associated IFN-γ/Ifngr1 complexes. Our study identifies a mechanism of cellular signaling regulated by EV-associated IFN-γ/Ifngr1 complexes, which grafted stem cells may use to communicate with the host immune system.
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