Proteins secreted by brain arteriolar smooth muscle cells are instructive for neural development.

Proteins secreted by brain arteriolar smooth muscle cells are instructive for neural development.
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DOI:
10.1186/s13041-022-00983-y
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发表时间:
2022-11-30
期刊:
影响因子:
3.6
通讯作者:
Jia, Jie-Min
Jia, Jie-Min
中科院分区:
医学3区
文献类型:
--
作者:
Li, Xuzhao;Zhou, Lili;Zhang, Xiaoxuan;Jin, Yuxiao;Zhao, Bingrui;Zhang, Dongdong;Xi, Chengjie;Ruan, Jiayu;Zhu, Zhu;Jia, Jie-Min

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由可扩散蛋白介导的血管和神经细胞之间的细胞间通讯最近成为神经发育的关键内在程序。然而,血管平滑肌细胞(VSMC)分泌组是否调节神经回路的连通性仍不清楚。在这里,我们表明,从脑VSMC培养条件培养基增强多种神经元功能,如轴突发生,神经元成熟,和生存,从而提高电路连接。然而,通过加热使蛋白质变性损害了这些效果。供体VSMC分泌组和受体神经元转录组的组合组学分析显示,细胞外基质受体信号传导和粘附分子整合素结合的重叠途径介导VSMC依赖的神经元发育。此外,我们发现,人动脉VSMCs促进神经元发育的多种方式,包括扩大新生神经突起始的时间窗口,增加神经元密度,并促进同步发射,而人脐静脉VSMCs缺乏这种能力。这些体外实验数据表明,脑小动脉VSMCs可能通过体内细胞间通讯为神经发育提供直接的指导信息。在线版本包含补充材料,可通过10.1186/s13041-022-00983-y获得。
Intercellular communication between vascular and nerve cells mediated by diffusible proteins has recently emerged as a critical intrinsic program for neural development. However, whether the vascular smooth muscle cell (VSMC) secretome regulates the connectivity of neural circuits remains unknown. Here, we show that conditioned medium from brain VSMC cultures enhances multiple neuronal functions, such as neuritogenesis, neuronal maturation, and survival, thereby improving circuit connectivity. However, protein denaturation by heating compromised these effects. Combined omics analyses of donor VSMC secretomes and recipient neuron transcriptomes revealed that overlapping pathways of extracellular matrix receptor signaling and adhesion molecule integrin binding mediate VSMC-dependent neuronal development. Furthermore, we found that human arterial VSMCs promote neuronal development in multiple ways, including expanding the time window for nascent neurite initiation, increasing neuronal density, and promoting synchronized firing, whereas human umbilical vein VSMCs lack this capability. These in vitro data indicate that brain arteriolar VSMCs may carry direct instructive information for neural development through intercellular communication in vivo. The online version contains supplementary material available at 10.1186/s13041-022-00983-y.
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