Dataset Information

LncRNA and mRNA Expression Profiles in Methylprednisolone Stimulated Neural Stem Cells.

ABSTRACT: Spinal cord injury (SCI) is a devastating neurological disorder that affects thousands of individuals each year. Previously, our study in non-human primates with SCI demonstrated that methylprednisolone (MP) resulted in the dysfunction of neural stem cells (NSCs), which may help to explain the controversial roles of MP in SCI. However, the detailed mechanism is still unclear. In this manuscript, we investigated the LncRNA and mRNA expression profiles of NSCs treated with MP. A total of 63 differentially expressed LncRNAs and 174 differentially expressed mRNAs were identified. Gene ontology (GO) analysis showed that differentially expressed mRNAs were highly associated with terms related to regulation of external stimulation, secretion, and migration. Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis results indicated that the PI3K-Akt signaling pathway contributed to the functions of MP treated NSCs. Besides, 3899 co-expression pairs were constructed among the differentially expressed LncRNA and mRNA, among which five predicted target mRNAs with the differentially expressed LncRNAs were identified. These results provide greater insight into the precise mechanisms of MP mediating NSC dysfunction in SCI.

SUBMITTER: Tang Y

PROVIDER: S-EPMC8262496 | biostudies-literature | 2021

REPOSITORIES: biostudies-literature

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LncRNA and mRNA Expression Profiles in Methylprednisolone Stimulated Neural Stem Cells.

Tang Yong Y Xie Zhongyu Z Ma Mengjun M Duan Kaidi K Li Yuxi Y Ye Jichao J

Frontiers in neuroscience 20210623

Spinal cord injury (SCI) is a devastating neurological disorder that affects thousands of individuals each year. Previously, our study in non-human primates with SCI demonstrated that methylprednisolone (MP) resulted in the dysfunction of neural stem cells (NSCs), which may help to explain the controversial roles of MP in SCI. However, the detailed mechanism is still unclear. In this manuscript, we investigated the LncRNA and mRNA expression profiles of NSCs treated with MP. A total of 63 differ ...[more]

PMID: 34248482

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Project description:Objective: Articular cartilage injury is common and difficult to treat clinically because of the characteristics of the cartilage. Bone marrow-derived mesenchymal stem cell (BMSC)-mediated cartilage regeneration is a promising therapy for treating articular cartilage injury. BMSC differentiation is controlled by numerous molecules and signaling pathways in the microenvironment at both the transcriptional and post-transcriptional levels. However, the possible function of super enhancer long non-coding RNAs (SE-lncRNAs) in the chondrogenic differentiation of BMSCs is still unclear. Our intention was to explore the expression profile of SE-lncRNAs and potential target genes regulated by SE-lncRNAs during chondrogenic differentiation in BMSCs. Materials and Methods: In this study, we conducted a human Super-Enhancer LncRNA Microarray to investigate the differential expression profile of SE-lncRNAs and mRNAs during chondrogenic differentiation of BMSCs. Subsequent bioinformatic analysis was performed to clarify the important signaling pathways, SE-lncRNAs, and mRNAs associated with SE-lncRNAs regulating the chondrogenic differentiation of BMSCs. Results: A total of 77 SE-lncRNAs were identified, of which 47 were upregulated and 30 were downregulated during chondrogenic differentiation. A total of 308 mRNAs were identified, of which 245 were upregulated and 63 were downregulated. Some pathways, such as focal adhesion, extracellular matrix (ECM)-receptor interaction, transforming growth factor-β (TGF-β) signaling pathway, and PI3K-Akt signaling pathway, were identified as the key pathways that may be implicated in the chondrogenic differentiation of BMSCs. Moreover, five potentially core regulatory mRNAs (PMEPA1, ENC1, TES, CDK6, and ADIRF) and 37 SE-lncRNAs in chondrogenic differentiation were identified by bioinformatic analysis. Conclusion: We assessed the differential expression levels of SE-lncRNAs and mRNAs, along with the chondrogenic differentiation of BMSCs. By analyzing the interactions and co-expression, we identified the core SE-lncRNAs and mRNAs acting as regulators of the chondrogenic differentiation potential of BMSCs. Our study also provided novel insights into the mechanism of BMSC chondrogenic and cartilage regeneration.

Project description:BackgroundThe goals of this study were to explore the expression profiles and functional networks of long non-coding RNAs (lncRNAs) and messenger RNAs (mRNAs) in mesenchymal stromal cells (MSCs) involved in regulating the function of monocytes and to clarify the mechanisms by which MSCs exert immunoregulatory effects on monocytes.MethodsMSCs and CD14+ monocytes were separately isolated. The immunoregulatory effects of MSCs on monocytes were determined by flow cytometry. lncRNAs and mRNAs that were differentially expressed (DE) between the control group (MSCs only) and co-culture group (MSCs co-cultured with monocytes) were identified through high-throughput sequencing and bioinformatic analyses and were confirmed by qRT-PCR. Bioinformatic analyses were performed to identify the critical biological functions and signalling pathways involved in MSC-mediated monocyte regulation and to identify the functional networks formed between DE mRNAs and lncRNAs.ResultsMSCs showed a strong ability to induce monocyte migration but inhibited monocyte differentiation into M1 macrophages. A total of 145 DE lncRNAs and 768 DE mRNAs were identified between the control and co-culture groups. Significant fold changes in lncRNAs and mRNAs were confirmed by qRT-PCR. GO analysis demonstrated that DE mRNAs and lncRNAs were highly associated with terms related to binding and biological regulation. KEGG analysis revealed 122 significantly regulated pathways, including the cytokine-cytokine receptor pathway and chemokine signalling pathway. Interaction and co-expression networks were constructed for DE mRNAs and lncRNAs, and several key microRNAs were identified in the competitive endogenous RNA (ceRNA) network. Target genes of the DE lncRNAs were analysed to predict critical mRNA-lncRNA axes involved in the immunoregulatory function of MSCs.ConclusionsOur research describes the lncRNA and mRNA expression profiles and functional networks involved in MSC-mediated regulation of monocytes. These results provide possible molecular mechanisms for the immunoregulatory function of MSCs and may help to elucidate possible molecular therapeutic targets in MSCs for the treatment of autoimmune diseases.

Dataset Information

LncRNA and mRNA Expression Profiles in Methylprednisolone Stimulated Neural Stem Cells.

Publications

LncRNA and mRNA Expression Profiles in Methylprednisolone Stimulated Neural Stem Cells.

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