Ceramide releases exosomes with a specific miRNA signature for cell differentiation

Exosomes are well established effectors of cell–cell communication. Their role on maturation of embryonic cells located in hippocampus, seat of memory, is unknown. University of Perugia researchers show that ceramide facilitates release of exosomes from HN9.10e cells extending information for cell differentiation to neighboring cells. The researchers found only 38 miRNAs differentially expressed in exosomes derived from ceramide-treated cells in comparison with control cells (including 10 up-regulated and 28 down-regulated). Some overexpressed miRNAs (mmu-let-7f-1-3p, mmu-let-7a-1-3p, mmu-let-7b-3p, mmu-let-7b-5p, mmu-miR-330-3p) regulate genes encoding for protein involved in biological, homeostatic, biosynthetic and small molecule metabolic processes, embryo development and cell differentiation, all phenomena relevant for HN9.10e cell differentiation. Notably, the overexpressed mmu-let-7b-5p miRNA appears to be important for this study based on its ability to regulate thirty-five gene targets involved in many processes including sphingolipid metabolism, sphingolipid-related stimulation of cellular functions and neuronal development. Furthermore, the researchers showed that by incubating embryonic cells with exosomes released under ceramide treatment, some cells acquired an astrocytic phenotype and others a neuronal phenotype. They anticipate this study to be a start point for innovative therapeutic strategies to regulate the release of exosomes useful to stimulate delayed brain development in the newborn and to improve the cognitive decline in neurodegenerative disorders.

Exosomal miRNA profiling of HN9.10e cells treated with ceramide

Figure 3

Heatmap showing the statistically significant differentially expressed miRNAs in HN9.10e cells treated with ceramide. Globally, thirty-eight transcripts (n = 10 up-regulated, n = 28 down-regulated) were differentially expressed in the exosomes of HN9.10e cells treated with ceramide, compared to controls (abs(logFC) ≥ 0.6, q-value ≤ 0.05). Hierarchical clustering of transcripts and samples using the Euclidean distance and the complete agglomeration method; expression data was vst-transformed, scaled and centered. When not available, the miRBase accession number was replaced by the ENSEMBL GeneID. The heatmap was generated using the DESeq2 R package (v.1.0.12).

Fiorani F, Domenis R, Dalla E. et al. (2023) Ceramide releases exosomes with a specific miRNA signature for cell differentiation. Sci Rep [Epub ahead of print]. [article]

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