FGF2-induced effects on transcriptome associated with regeneration competence in adult human fibroblasts

Olga Kashpur,Tanja Dominko,Elizabeth F Ryder,David Lapointe,Sakthikumar Ambady

doi:10.1186/1471-2164-14-656

Abstract

BackgroundAdult human fibroblasts grown in low oxygen and with FGF2 supplementation have the capacity to tip the healing outcome of skeletal muscle injury – by favoring regeneration response in vivo over scar formation. Here, we compare the transcriptomes of control adult human dermal fibroblasts and induced regeneration-competent (iRC) fibroblasts to identify transcriptional changes that may be related to their regeneration competence.ResultsWe identified a unique gene-expression profile that characterizes FGF2-induced iRC fibroblast phenotype. Significantly differentially expressed genes due to FGF2 treatment were identified and analyzed to determine overrepresented Gene Ontology terms. Genes belonging to extracellular matrix components, adhesion molecules, matrix remodelling, cytoskeleton, and cytokines were determined to be affected by FGF2 treatment.ConclusionsTranscriptome analysis comparing control adult human fibroblasts with FGF2-treated fibroblasts identified functional groups of genes that reflect transcriptional changes potentially contributing to their regeneration competence. This comparative transcriptome analysis should contribute new insights into genes that characterize cells with greater regenerative potential.

Highlights

Adult human fibroblasts grown in low oxygen and with FGF2 supplementation have the capacity to tip the healing outcome of skeletal muscle injury – by favoring regeneration response in vivo over scar formation
The effect of cell growth surface and FGF2 on fibroblast transcriptome To obtain a sense of the effects of surface and FGF2 treatment on global transcription, two independent samples of human dermal fibroblasts grown on glass, glass with FGF2, plastic, and plastic with FGF2 were hybridized to the Human Whole Genome OneArray® microarray, which contains 29,187 human oligonucleotide probes
To investigate cell culture effects, we examined significantly differentially expressed gene probes using moderated t-statistic and based on the false discovery rate (FDR) cutoff value of 0.05

Summary

Introduction

Adult human fibroblasts grown in low oxygen and with FGF2 supplementation have the capacity to tip the healing outcome of skeletal muscle injury – by favoring regeneration response in vivo over scar formation. Analyzing the transcriptome of a cell type offers an opportunity to broadly identify transcripts that define it In addition to these either developmentally regulated or artificially induced phenotype changes that are accompanied by distinct transcriptional changes, a transcriptome of any given cell type can vary substantially depending on cell cycle [1,2,3], passage number, and environmental factors such as oxygen concentration [4], temperature, and presence of serum [5]. Another important factor that causes transcriptional changes and is crucial for maintaining a cell phenotype is growth substrate. Smooth and rigid glass surface supports undifferentiated phenotype, while rough and soft substrates promote differentiation [13,14]

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Conclusion