Abstract
BackgroundMesangial cells play an important role in the glomerulus to provide mechanical support and maintaine efficient ultrafiltration of renal plasma. Loss of mesangial cells due to pathologic conditions may lead to impaired renal function. Mesenchymal stem cells (MSC) can differentiate into many cell types, including mesangial cells. However transcriptomic profiling during MSC differentiation into mesangial cells had not been studied yet. The aim of this study is to examine the pattern of transcriptomic changes during MSC differentiation into mesangial cells, to understand the involvement of transcription factor (TF) along the differentiation process, and finally to elucidate the relationship among TF-TF and TF-key gene or biomarkers during the differentiation of MSC into mesangial cells.ResultsSeveral ascending and descending monotonic key genes were identified by Monotonic Feature Selector. The identified descending monotonic key genes are related to stemness or regulation of cell cycle while ascending monotonic key genes are associated with the functions of mesangial cells. The TFs were arranged in a co-expression network in order of time by Time-Ordered Gene Co-expression Network (TO-GCN) analysis. TO-GCN analysis can classify the differentiation process into three stages: differentiation preparation, differentiation initiation and maturation. Furthermore, it can also explore TF-TF-key genes regulatory relationships in the muscle contraction process.ConclusionsA systematic analysis for transcriptomic profiling of MSC differentiation into mesangial cells has been established. Key genes or biomarkers, TFs and pathways involved in differentiation of MSC-mesangial cells have been identified and the related biological implications have been discussed. Finally, we further elucidated for the first time the three main stages of mesangial cell differentiation, and the regulatory relationships between TF-TF-key genes involved in the muscle contraction process. Through this study, we have increased fundamental understanding of the gene transcripts during the differentiation of MSC into mesangial cells.
Highlights
Mesangial cells play an important role in the glomerulus to provide mechanical support and maintaine efficient ultrafiltration of renal plasma
TO-gene co-expression network (GCN) with 9 levels was constructed from these 1191 transcription factor (TF) genes (Fig. 1) and a list of these TF genes was supplemented in Additional file 2
We demonstrated that genes with ascending or descending monotonic expression patterns in chronological stem cell data are involved in differentiation of stem cells into variant cell lineages or the proliferation or self-renewal activity of stem cells [12]
Summary
Mesangial cells play an important role in the glomerulus to provide mechanical support and maintaine efficient ultrafiltration of renal plasma. Loss of mesangial cells due to pathologic conditions may lead to impaired renal function. Transcriptomic profiling during MSC differentiation into mesangial cells had not been studied yet. Mesangial cells have the characteristics of specialized renal pericytes and are capable of a number of other functions Their contractile properties enable mesangial cells to alter intraglomerular capillary flow and glomerular ultrafiltration surface [2]. These cells perform phagocytosis and endocytosis in which these cells take up residues such as ferritin, colloidal carbon and aggregated proteins [3]. The gene expression or transcriptomic profiling during MSC differentiation into mesangial cells has not been studied yet
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