Network analysis for the identification of hub genes and related molecules as potential biomarkers associated with the differentiation of bone marrow-derived stem cells into hepatocytes

Abstract

The incidence of liver diseases has been increasing steadily. However, it has some shortcomings, such as high cost and organ donor scarcity. The application of stem cell research has brought new ideas for the treatment of liver diseases. Therefore, it is particularly important to clarify the molecular and regulatory mechanisms of differentiation of bone marrow-derived stem cells (BMSCs) into liver cells. Herein, we screened differentially expressed genes between hepatocytes and untreated BMSCs to identify the genes responsible for the differentiation of BMSCs into hepatocytes. GSE30419 gene microarray data of BMSCs and GSE72088 gene microarray data of primary hepatocytes were obtained from the Gene Expression Omnibus database. Transcriptome Analysis Console software showed that 1896 genes were upregulated and 2506 were downregulated in hepatocytes as compared with BMSCs. Hub genes were analyzed using the STRING and Cytoscape v 3.8.2, revealing that twenty-four hub genes, play a pivotal role in the differentiation of BMSCs into hepatocytes. The expression of the hub genes in the BMSCs and hepatocytes was verified by reverse transcription-quantitative PCR (RT-qPCR). Next, the target miRNAs of hub genes were predicted, and then the lncRNAs regulating miRNAs was discovered, thus forming the lncRNA-miRNA-mRNA interaction chain. The results indicate that the lncRNA-miRNA-mRNA interaction chain may play an important role in the differentiation of BMSCs into hepatocytes, which provides a new therapeutic target for liver disease treatment.

Transformation of an olfactory placode-derived cell into one with stem cell characteristics by disrupting epigenetic barriers

“…Among the most significantly up-regulated genes in these two colony-dominated clusters were Cyclin Dependent Kinase 8 (CDK8), Calcium/Calmodulin Dependent Protein Kinase ID (Camk1d), and translation-associated genes Cmss1 and Lars2, as well as the Metallothionein 1 (Mt1) gene and the GM42418 cell differentiation lincRNA. The GM42418 gene is a marker for hepatocyte cell differentiation (Han et al, 2022) and the Mt1 gene encodes a metal-binding protein that has been closely linked with the regulation of cell proliferation and immune cell differentiation (Dai et al, 2021). The other four genes (CDK8, Camk1d, Cmss1, and Lars2) are putative factors that regulate pluripotent embryonic stem cells (ESCs) (Adler et al, 2012; Bergamaschi et al, 2008; Feng et al, 2022; Wang and Amoyel, 2022).…”