مقالات پذیرفته شده در نهمین کنگره بین المللی زیست پزشکی
Transcriptomic Insights into lncRNA-Mediated Control of Mitochondrial Function and Differentiation in Bone Marrow- and Dental Pulp-Derived MSCs
Transcriptomic Insights into lncRNA-Mediated Control of Mitochondrial Function and Differentiation in Bone Marrow- and Dental Pulp-Derived MSCs
Nima Ghasemi,1Hossein Azizi,2,*Melika Emarati,3
1. Department of Applied Biotechnology and System Biology, College of Biotechnology, Amol University of Special Modern Technologies, Amol, Iran 2. Department of Stem Cells and Cancer, College of Biotechnology, Amol University of Special Modern Technologies, Amol, Iran 3. Department of Applied Biotechnology and System Biology, College of Biotechnology, Amol University of Special Modern Technologies, Amol, Iran
Introduction: Mesenchymal stem cells (MSCs) from bone marrow (BMSCs) and dental pulp (DPSCs) display distinct lineage commitment and tumorigenic potential, with DPSCs showing greater osteogenic capacity and resistance to oncogenic transformation. While the PTEN/PI3K/AKT pathway is known to contribute to these differences, the role of broader regulatory networks, especially those involving long non-coding RNAs (lncRNAs), is not fully understood. This study investigates the transcriptomic differences between these cell types to identify lncRNA-mediated regulatory hubs that govern their unique biological identities.
Methods: We performed a comprehensive bioinformatic analysis of the RNA-Seq dataset GSE105145, comparing three biological replicates of BMSCs and DPSCs. Differential gene expression analysis was conducted using the DESeq2 package in R, with a significance threshold of an adjusted p-value < 0.05. An lncRNA-mRNA co-expression network was constructed by calculating the Pearson correlation between the top 100 differentially expressed lncRNAs and all significantly expressed protein-coding genes. Genes with a correlation coefficient (r) > 0.7 were considered strongly correlated. Functional enrichment analysis was then performed on the top 500 genes most correlated with the primary hub lncRNA to identify over-represented biological pathways.
Results: The analysis identified a significant number of differentially expressed genes between BMSCs and DPSCs. A hub lncRNA was identified that was strongly co-expressed with a large network of protein-coding genes, including key developmental regulators such as CRIP2, KLF2, FHL2, and ANKRD1. Functional enrichment analysis of this network revealed a significant overrepresentation of pathways related to mitochondrial function and metabolism, including "The citric acid (TCA) cycle and respiratory electron transport" (p = 3.46 × 10^-7) and "Oxidative phosphorylation" (p = 9.67 × 10^-6). Furthermore, pathways directly linked to lineage potential, such as "Embryonic skeletal system development" (p = 1.18 × 10^-9), were also highly enriched.
Conclusion: Our findings reveal a lncRNA-centered regulatory network that is strongly associated with mitochondrial metabolism and skeletal system development. This network appears to be a key driver of the distinct functional differences observed between BMSCs and DPSCs. By coordinating critical gene expression programs, this hub lncRNA helps define the unique lineage commitment and tumorigenic susceptibility of these stem cell populations, highlighting a potential new target for therapeutic intervention.