RNA sequencing from human neutrophils reveals distinct transcriptional differences associated with chronic inflammatory states

RNA sequencing from human neutrophils reveals distinct transcriptional differences associated with chronic inflammatory states
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DOI:
10.1186/s12920-015-0128-7
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发表时间:
2015-08-27
影响因子:
2.7
通讯作者:
Jarvis, James N.
Jarvis, James N.
中科院分区:
医学3区
文献类型:
--
作者:
Jiang, Kaiyu;Sun, Xiaoyun;Jarvis, James N.

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背景:哺乳动物细胞转录的复杂性表明它们有广泛的能力对特定的环境刺激和生理环境做出反应。这些能力从哺乳动物基因组的结构中并不是先验的,但已经通过详细的转录组分析得到了鉴定。在这项研究中,我们使用RNA测序(RNAseq)技术检测了先天免疫系统--人类中性粒细胞的转录产物。方法:我们从9个个体样本中测序了Poly-A RNA,这些个体样本对应于特定的表型:3个未经治疗的儿童特发性关节炎(JIA),3个相同疾病的疾病不活跃的药物治疗(CRM),以及3个囊性纤维化(CF)。结果:我们证明,中性粒细胞的转录产物,通常被认为在其反应和功能上是非特异性的,其转录谱具有相当大的特异性,依赖于病理背景,包括基因、基因同工形式和基因和长的非编码RNA转录本。此外,尽管样本数很少,但这些发现证明了RNAseq方法在风湿病生物标记物开发中的潜力。结论:这些数据表明,以前被认为在功能上非特异性的细胞有能力使其转录适应特定的生物环境。这些数据还提供了对以前未知的病理途径的洞察,并在阐明疾病和疾病状态特定的调控网络方面显示出相当大的希望。
Background: The transcriptional complexity of mammalian cells suggests that they have broad abilities to respond to specific environmental stimuli and physiologic contexts. These abilities were not apparent a priori from the structure of mammalian genomes, but have been identified through detailed transcriptome analyses. In this study, we examined the transcriptomes of cells of the innate immune system, human neutrophils, using RNA sequencing (RNAseq).Methods: We sequenced poly-A RNA from nine individual samples corresponding to specific phenotypes: three children with active, untreated juvenile idiopathic arthritis (JIA)(AD), three children with the same disease whose disease was inactive on medication (CRM), and three children with cystic fibrosis (CF).Results: We demonstrate that transcriptomes of neutrophils, typically considered non-specific in their responses and functions, display considerable specificity in their transcriptional repertoires dependent on the pathologic context, and included genes, gene isoforms, and long non-coding RNA transcripts. Furthermore, despite the small sample numbers, these findings demonstrate the potential of RNAseq approaches to biomarker development in rheumatic diseases.Conclusions: These data demonstrate the capacity of cells previously considered non-specific in function to adapt their transcriptomes to specific biologic contexts. These data also provide insight into previously unrecognized pathological pathways and show considerable promise for elucidating disease and disease-state specific regulatory networks.