Cooperative and competitive regulation of the astrocytic transcriptome by neurons and endothelial cells: Impact on astrocyte maturation.
astrocyte maturation
astrocyte-blood vessel interaction
astrocyte-neuron interaction
astrocytes
neurovascular coupling
transcriptomics
Journal
Journal of neurochemistry
ISSN: 1471-4159
Titre abrégé: J Neurochem
Pays: England
ID NLM: 2985190R
Informations de publication
Date de publication:
10 2023
10 2023
Historique:
revised:
19
06
2023
received:
01
03
2023
accepted:
20
06
2023
pmc-release:
01
10
2024
medline:
4
10
2023
pubmed:
1
8
2023
entrez:
1
8
2023
Statut:
ppublish
Résumé
Astrocytes have essential roles in central nervous system (CNS) health and disease. During development, immature astrocytes show complex interactions with neurons, endothelial cells, and other glial cell types. Our work and that of others have shown that these interactions are important for astrocytic maturation. However, whether and how these cells work together to control this process remains poorly understood. Here, we test the hypothesis that cooperative interactions of astrocytes with neurons and endothelial cells promote astrocytic maturation. Astrocytes were cultured alone, with neurons, endothelial cells, or a combination of both. This was followed by astrocyte sorting, RNA sequencing, and bioinformatic analysis to detect transcriptional changes. Across culture configurations, 7302 genes were differentially expressed by 4 or more fold and organized into 8 groups that demonstrate cooperative and antagonist effects of neurons and endothelia on astrocytes. We also discovered that neurons and endothelial cells caused splicing of 200 and 781 mRNAs, respectively. Changes in gene expression were validated using quantitative PCR, western blot (WB), and immunofluorescence analysis. We found that the transcriptomic data from the three-culture configurations correlated with protein expression of three representative targets (FAM107A, GAT3, and GLT1) in vivo. Alternative splicing results also correlated with cortical tissue isoform representation of a target (Fibronectin 1) at different developmental stages. By comparing our results to published transcriptomes of immature and mature astrocytes, we found that neurons or endothelia shift the astrocytic transcriptome toward a mature state and that the presence of both cell types has a greater effect on maturation than either cell alone. These results increase our understanding of cellular interactions/pathways that contribute to astrocytic maturation. They also provide insight into how alterations to neurons and/or endothelial cells may alter astrocytes with implications for astrocytic changes in CNS disorders and diseases.
Identifiants
pubmed: 37525469
doi: 10.1111/jnc.15908
pmc: PMC10543513
mid: NIHMS1915468
doi:
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
52-75Subventions
Organisme : NICHD NIH HHS
ID : U54 HD086984
Pays : United States
Organisme : NINDS NIH HHS
ID : R01 NS106693
Pays : United States
Organisme : NINDS NIH HHS
ID : R01 NS092067
Pays : United States
Organisme : NICHD NIH HHS
ID : P50 HD105354
Pays : United States
Informations de copyright
© 2023 The Authors. Journal of Neurochemistry published by John Wiley & Sons Ltd on behalf of International Society for Neurochemistry.
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