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

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. H...

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Bibliographic Details
Published in:Molecular brain 2022-11, Vol.15 (1), p.97-97, Article 97
Main Authors: Li, Xuzhao, Zhou, Lili, Zhang, Xiaoxuan, Jin, Yuxiao, Zhao, Bingrui, Zhang, Dongdong, Xi, Chengjie, Ruan, Jiayu, Zhu, Zhu, Jia, Jie-Min
Format: Article
Language:English
Subjects:
Axonogenesis
Biological Transport
Brain
Brain research
Cell culture
Cell interactions
Conditioned medium
Denaturation
Extracellular matrix
Humans
Integrins
Laboratory animals
Morphogenesis
Myocytes, Smooth Muscle
Nervous system
Neural circuitry
Neural development
Neural networks
Neuritogenesis
Neurogenesis
Neurons
Neurophysiology
Protein denaturation
Proteins
Secretome
Smooth muscle
Synchronized activity
Transcriptomes
Umbilical vein
Vascular smooth muscle cell (VSMC)
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Summary: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.
ISSN:1756-6606
1756-6606
DOI:10.1186/s13041-022-00983-y