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人类大脑发育过程中分子线索的细胞外囊泡介导转运。

Extracellular vesicle-mediated trafficking of molecular cues during human brain development.

机构信息

Max Planck Institute of Psychiatry, Munich, Germany; Division of Physiological Genomics, Biomedical Center (BMC), Faculty of Medicine, Ludwig Maximilian University (LMU), Munich, Germany.

Max Planck Institute of Psychiatry, Munich, Germany; International Max Planck Research School for Translational Psychiatry, Munich, Germany.

出版信息

Cell Rep. 2024 Oct 22;43(10):114755. doi: 10.1016/j.celrep.2024.114755. Epub 2024 Sep 19.

DOI:10.1016/j.celrep.2024.114755
PMID:39302835
Abstract

Cellular crosstalk is an essential process influenced by numerous factors, including secreted vesicles that transfer nucleic acids, lipids, and proteins between cells. Extracellular vesicles (EVs) have been the center of many studies focusing on neurodegenerative disorders, but whether EVs display cell-type-specific features for cellular crosstalk during neurodevelopment is unknown. Here, using human-induced pluripotent stem cell-derived cerebral organoids, neural progenitors, neurons, and astrocytes, we identify heterogeneity in EV protein content and dynamics in a cell-type-specific and time-dependent manner. Our results support the trafficking of key molecules via EVs in neurodevelopment, such as the transcription factor YAP1, and their localization to differing cell compartments depending on the EV recipient cell type. This study sheds new light on the biology of EVs during human brain development.

摘要

细胞串扰是一个受多种因素影响的重要过程,包括细胞间传递核酸、脂质和蛋白质的分泌小泡。细胞外囊泡 (EVs) 一直是许多关注神经退行性疾病的研究的中心,但 EVs 是否在神经发育过程中表现出细胞类型特异性的细胞串扰特征尚不清楚。在这里,我们使用人类诱导多能干细胞衍生的大脑类器官、神经祖细胞、神经元和星形胶质细胞,以细胞类型特异性和时间依赖性的方式鉴定了 EV 蛋白含量和动力学的异质性。我们的结果支持关键分子通过 EV 在神经发育中的运输,例如转录因子 YAP1,并且根据 EV 受体细胞类型,它们定位到不同的细胞区室。这项研究为人类大脑发育过程中 EV 的生物学提供了新的视角。

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