Abstract
Skin-derived precursors (SKPs) from dermis possess the capacities of self-renewal and multipotency. In vitro and in vivo studies demonstrated that they can differentiate into fibroblasts. However, little is known about the molecular mechanism of the differentiation of SKPs into fibroblasts. Here we compare the transcriptomes of mouse SKPs and SKP-derived fibroblasts (SFBs) by RNA-Seq analysis, trying to find differences in gene expression between the two kinds of cells and then elucidate the candidate genes that may play important roles in the differentiation of SKPs into fibroblasts. A total of 1971 differentially expressed genes (DEGs) were identified by RNA-Seq, which provided abundant data for further analysis. Gene Ontology enrichment analysis revealed that genes related to cell differentiation, cell proliferation, protein binding, transporter activity and membrane were significantly enriched. The most significantly up-regulated genes Wnt4, Wisp2 and Tsp-1 and down-regulated genes Slitrk1, Klk6, Agtr2, Ivl, Msx1, IL15, Atp6v0d2, Kcne1l and Thbs4 may play important roles in the differentiation of SKPs into fibroblasts. KEGG analysis showed that DEGs were significantly enriched in the TGF-β signaling pathway, Wnt signaling pathway and Notch signaling pathway, which have been previously proven to regulate the differentiation and self-renewal of various stem cells. These identified DEGs and pathways could facilitate further investigations of the detailed molecular mechanisms, making it possible to take advantage of the potential therapeutic applications of SKPs in skin regeneration in the future.
Highlights
Recent developments in stem cell biology have generated much excitement about the potential for regenerative medicine and cell-based therapies in a variety of clinical applications, such as treating leukemia, Parkinson’s disease and wounds
Transcriptomes of SKPs and SKP-Derived Fibroblasts by RNA-Seq transplantation, stem cells isolated from skin could be promising candidates for prospective therapeutic applications
SKPs attached to the bottom of poly-L-lysine treated dishes and exhibited fibroblast-like morphology(Fig. 1B and C) 3 days after serum induction
Summary
Recent developments in stem cell biology have generated much excitement about the potential for regenerative medicine and cell-based therapies in a variety of clinical applications, such as treating leukemia, Parkinson’s disease and wounds. Skin-derived precursors(SKPs) from dermis possess the capacities of self-renewal and multipotency [1,2]. They can differentiate into cells of both neural and mesodermal lineages, such as neurons, glias, smooth muscle cells, osteogenic and adipogenic cells [1,2,3,4,5]. When attached onto culture dishes by serum, SKPs initiated differentiation and developed into a fibroblast-like morphology. These SKP-derived fibroblasts(SFBs) could express fibroblast markers fibronectin and vimentin, but did not express SKP marker nestin [6]. Given that SKPs can differentiate into fibroblasts, they might be useful for treating aged skin or regenerating skin after damage since they can replenish lost or damaged fibroblasts
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