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RNA-sequencing indicates age-dependent shifts in the cardiac fibroblast transcriptome between fetal, neonatal, and adult developmental ages
Physiological Genomics ( IF 4.6 ) Pub Date : 2021-07-19 , DOI: 10.1152/physiolgenomics.00074.2021
Luke R Perreault 1 , Thanh T Le 1 , Madeleine J Oudin 1, 2 , Lauren D Black 1, 2
Affiliation  

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 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.

中文翻译:

RNA 测序表明胎儿、新生儿和成人发育年龄之间心脏成纤维细胞转录组的年龄依赖性变化

背景:心脏成纤维细胞负责心脏环境中的细胞外基质更新和修复,并有助于促进免疫反应。然而,众所周知,它们在位置、生理条件和发育年龄方面具有显着的表型异质性。本研究的目的是提供来自胎儿、新生儿和成人发育年龄的大鼠心脏的心脏成纤维细胞的深入转录组学特征,以确定可能在这些特定发育阶段驱动这些细胞功能差异的基因表达变化. 结果:我们对从胎儿、新生和成年大鼠中分离的心脏成纤维细胞进行了 RNA-seq,并与大鼠基因组进行了比较。RNA-seq 数据的主成分分析表明数据差异主要是由于发育年龄。针对基因本体论和京都基因和基因组百科全书数据集的差异表达和基因集富集分析表明,发育年龄存在一系列差异,包括心脏发育和心脏功能相关基因随年龄增长显着下降,以及免疫和炎症显着增加-与发育年龄增加相关的功能 - 特别是免疫细胞信号传导以及细胞因子和趋化因子的产生。结论:这些结果强化了成纤维细胞在发育年龄方面的不同表型异质性的既定证据。此外,根据我们对基因表达的分析,
更新日期:2021-07-20
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