Abstract
Circular RNAs (circRNAs) are crucial elements of non-coding RNA, that regulate various biological processes. To date, expression patterns and functional roles of circRNAs during osteogenic differentiation of human umbilical cord mesenchymal stromal cells (hUCMSCs) remain unknown. In this study, we analyzed RNA-sequence data to reveal expression profiles of circRNAs during osteogenesis of hUCMSCs, then elucidated the underlying mechanisms of action. We identified a total of 5457 circRNAs in hUCMSCs, of which 34 and 33 were upregulated and downregulated, respectively. We applied Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses to determine functions and related pathways of differentially expressed circRNAs. Moreover, we applied bioinformatics tools to construct competing endogenous RNA networks, comprising 10 circRNAs, 46 micro RNAs and 413 mRNAs. Furthermore, we predicted protein-coding potential of the upregulated circRNAs then constructed a co-expression network comprising the top 5 upregulated circRNAs and 75 RNA-binding proteins. Next, we validated 6 differentially-expressed circRNAs and found that overexpressing circ‐CTTN could promote osteogenesis of hUCMSCs. Overall, our findings indicate that clusters of circRNAs are aberrantly expressed in hUCMSCs during osteogenic differentiation, hence lay a foundation for future research into promoting hUCMSCs osteogenic differentiation and bone regeneration.
Highlights
Mesenchymal stromal cells (MSCs), which are characterized by multipotency characteristics, are found in many human tissues, such as bone marrow, skin, adipose and umbilical cord b lood[1]
MiR-4538 interacted with 3 circRNAs and 10 mRNAs, to participate in a variety of metabolic pathways during human umbilical cord mesenchymal stromal cells (hUCMSCs) osteogenic differentiation. These results indicated that the 10 circRNAs might be closely associated with gene regulation during osteogenic differentiation of hUCMSCs
We further investigated whether circ-CTTN impacts osteogenic differentiation and found that overexpressing this factor significantly promoted osteogenic differentiation of hUCMSCs
Summary
Mesenchymal stromal cells (MSCs), which are characterized by multipotency characteristics, are found in many human tissues, such as bone marrow, skin, adipose and umbilical cord b lood[1]. Bone marrow mesenchymal stromal cells (BMSCs) have been extensively studied for the reconstruction and regeneration of damaged tissues[2]. It is necessary to identify alternative sources of isolating MSCs. hUCMSCs, which can be collected from umbilical cord tissues of newborn infants, have been regarded as a favorable seed cell. These cells exhibit similar proliferation and osteogenic differentiation potential with those of BMSCs4,5. These findings indicate provide novel insights into understanding of osteogenic differentiation of mesenchymal stromal cells, and are expected to improve our knowledge of the circRNA modulation during osteogenic differentiation of hUCMSCs
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