Exosomes Originating from Neural Stem Cells Undergoing Necroptosis Participate in Cellular Communication Following Spinal Cord Injury

Abstract

Abstract In the aftermath of spinal cord injury (SCI), neural stem cells (NSCs) undergo programmed necroptosis, yet the alterations in exosomes and their associated functions remain unexplored. In this study, our data analysis briefly demonstrated that NSCs originate from ependymal cells and experience necroptosis through the classical pathway. Subsequently, NSCs were extracted from embryonic 16-17 mice. We established an in vitro necroptosis model and conducted exosomes extraction. Our findings revealed that necroptosis did not exert a significant impact on the fundamental properties and yield of exosomes. Subsequent to transcriptome sequencing, differentially expressed 108 mRNAs, 104 lncRNAs, 720 circRNAs, and 14 miRNAs were identified, with the first three significantly enriched for the ubiquitin-mediated proteolysis and autophagy signaling pathways. The construction of the competing endogenous RNA network was continued to screen for hubb genes including Tuberous sclerosis 2(Tcs2), Solute carrier family 16 member 3(Slc16a3) and Forkhead box protein P1(Foxp1). Further analysis of cellular communication after SCI revealed that Tsc2 was involved in ependymal cellular communication at 1 and 3 days after SCI through the EGF and MDK signaling pathways, while Slc16a3 participated in cellular communication in the control group and in ependymal cells at 7 days after SCI through the VEGF and MIF signaling pathways. This study introduces novel perspectives on the impacts of necroptosis in SCI.