RT Journal Article
SR Electronic
T1 RNA-sequencing indicates immune cell signaling and inflammatory gene expression in cardiac fibroblasts increases with developmental age
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2021.03.01.433442
DO 10.1101/2021.03.01.433442
A1 Luke R. Perreault
A1 Thanh T. Le
A1 Madeleine J. Oudin
A1 Lauren D. Black III
YR 2021
UL http://biorxiv.org/content/early/2021/03/01/2021.03.01.433442.abstract
AB Background Cardiac fibroblasts are responsible for extracellular matrix turnover and repair in the cardiac environment and serve to help facilitate immune responses. However, it is well established that they have significant phenotypic heterogeneity with respect to location, physiological conditions, and developmental age. The goal of this study was to provide an in-depth transcriptomic profile of cardiac fibroblasts derived from rat hearts at fetal, neonatal, and adult developmental ages to ascertain variations in gene expression that may drive functional differences in these cells at these specific stages of development.Results We performed RNA-seq of cardiac fibroblasts isolated from fetal, neonatal, and adult rats was performed and compared to the rat genome. Principal component analysis of RNA-seq data suggested data variance was predominantly due to developmental age. Differential expression and Gene set enrichment analysis against Gene Ontology and Kyoto Encyclopedia of Genes and Genomes datasets indicated an array of differences across developmental ages, including significant decreases in cardiac development and cardiac function-associated genes with age, and a significant increase in immune and inflammatory-associated functions - particularly immune cell signaling, and cytokine and chemokine production - with respect to increasing developmental age.Conclusion These results reinforce established evidence of diverse phenotypic heterogeneity of fibroblasts with respect to developmental age. Further, based on our analysis of gene expression, age-specific alterations in cardiac fibroblasts may play a crucial role in observed differences in cardiac inflammation and immune response observed across developmental ages.Competing Interest StatementThe authors have declared no competing interest.cDNAcomplementary deoxyribonucleic acidCFcardiac fibroblastCMcardiomyocyteDAPI4’,6-diamidino-2-phenylindoleDDR2discoidin domain receptor 2DNAdeoxyribonucleic acidECMextracellular matrixFBSfetal bovine serumGAPDHglyceraldehyde 3-phosphate dehydrogenaseGOgene ontologyILinterleukinKEGGKyoto Encyclopedia of Genes and GenomeslogFClog fold changeLPSlipopolysaccharideMMPmatrix metalloproteinaseMYHmyosin heavy chainmRNAmessenger ribonucleic acidPBSphosphate buffered salinePCAprincipal component analysisRNAribonucleic acidRNA-seqRNA sequencingRT-qPCRreverse transcriptase quantitative polymerase chain reaction