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Effects of naloxone on NSC proliferation and differentiation

ABSTRACT: Effects of naloxone on NSC proliferation and differentiation

PROVIDER: PRJNA416070 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR6228880.fastq.gz	Fastqsanger.gz
	SRR6228875.fastq.gz	Fastqsanger.gz
	SRR6228876.fastq.gz	Fastqsanger.gz
	SRR6228877.fastq.gz	Fastqsanger.gz
	SRR6228878.fastq.gz	Fastqsanger.gz

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Effects of naloxone on NSC proliferation and differentiation

Project description:Naloxone is an opioid-receptor antagonist used to reverse the effects of opioid.In our study, we treated NSCs (neural stem cells) with naloxone and damgo (a selective μopioid receptor agonist), and examined their effects on NSCs proliferation and differentiation.Naloxone was found to promote NSCs proliferation and neural differentiation, while the effects of damgo was very week. The results suggested that naloxone may work indepedent of opioid receptors. To investigate the underlying mechanisms, RNA-seq was conducted. For proliferation analysis,p8 NSCs were cultured with or without naloxone or damgo for 3 days. For differentiation analysis,p8 NSCs was induced to differentiate with or without naloxone or damgo, samples on D2 were collected and analyzed.

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Project description:Brain microenvironment plays an important role in neurodevelopment and function, where extracellular matrix (ECM) components and soluble factors modulate cellular features, as migration, proliferation survival and neuronal function. Disruption of microenvironment’s homeostasis is often related to pathological conditions. Here, we addressed the microenvironment remodeling occurring during in vitro differentiation of human neural stem cells (NSC) in a three-dimensional (3D) culture system. Proteome and transcriptome dynamics revealed significant changes namely at cell membrane and ECM composition during 3D differentiation, diverging significantly from the profile of monolayer cultures (2D). Structural proteoglycans typically found in brain ECM were enriched during 3D differentiation, while 2D cultures presented increased levels of basement membrane constituents (e.g., laminins, collagens and fibrillins). Moreover, higher expression levels of synaptic machinery and ion transport machinery constituents observed for 3D cultures, both at mRNA and protein levels, suggested a higher degree of neuronal maturation and organization relative to 2D differentiation. This work demonstrated that neural cellular and extracellular features can be recapitulated in the presented 3D neural cell model, highlighting its value to address molecular defects in cell-ECM interactions associated with neurological disorders. <html><head>Associated GEO dataset is available at</head><body><a href="https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi">GSE102139</a></body></html>

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