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lysophosphatidic 酸和斯芬戈辛-1-酸是多个有机体系统中的顶点极性线索

Andrew M Tidball¹, Jinghui Luo², J Clayton Walker²

¹Department of Neurology, University of Michigan Medical School, Ann Arbor, MI, USA; Michigan Neuroscience Institute, University of Michigan Medical School, Ann Arbor, MI, USA.

|June 12, 2025

概括

lysophosphatidic acid (LPA) 和sphingosine-1-phosphate (S1P) 是控制人类有机体细胞极性的关键信号分子. 这一发现揭示了LPA在组织和组织发育中的关键作用.

科学领域:

发展生物学发展生物学
细胞生物学细胞生物学
组织工程是组织工程.

背景情况:

基极化对于体内和有机体模型中的组织组织至关重要.
虽然细胞外矩阵 (ECM) 移除通常会逆转某些有机体的极性,但大脑有机体会保持极性,这表明媒介的影响.
之前的研究指出,在血清暴露后,大脑器官中出现了尖端向外的方向.

研究的目的:

为了识别影响无ECM大脑有机体中基极性的介质成分.
调查各种人类有机体系统中识别的极性线索的机制和更广泛的适用性.

主要方法:

培养没有ECM的人类大脑有机体,并将其暴露在血清和特定介质组件中.
使用 lysophosphatidic 酸 (LPA) 和斯芬戈辛-1-酸 (S1P) 作为候选极性线索.
进行药理学研究以阐明信号通路 (G蛋白结合受体/RhoA).
测试LPA对患者衍生的肺,肠道器官和iPSC球体的影响.

主要成果:

Lysophosphatidic 酸 (LPA) 被确定为诱导大脑器官在 1 天内产生尖端外极性的关键因素,持续时间超过一个月.
斯芬哥辛-1-酸盐 (S1P) 也诱导了类似的尖端外极化.
通过G蛋白合受体/RhoA通路进行LPA/S1P信号传递.
在不同的人类器官中,LPA成功诱导了顶端外极性,包括肺部,肠道和iPSC衍生的模型.

结论:

在没有ECM的人类大脑器官中,LPA信号是极点极性的关键决定因素.
LPA和S1P通过保留的G蛋白合受体/RhoA通路作用,以建立顶端外极性.
在多种人体器官类型中,LPA 作为一个关键的尖端极性线索,对组织发育和再生有影响.

关键词:

CP: 细胞生物学细胞生物学科普:干细胞研究在LPAR1中,罗罗罗罗罗罗罗罗罗顶端的-外的-外的基底极性 (apicobasal polarity) 是一个极性.大脑是一个有机体的器官.大脑脊髓液中的脑脊液.它的表皮质 (epithelium) 是一个表皮质.脂的信号传递方式紧密的结节紧密的结节

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