单细胞RNAseq通过减轻个体间采样异质性来识别PwCF中持续的上皮和免疫功能障碍
Thaddeus Cybulski1, Marc A Sala1, Trevor Nicholson2
1Division of Pulmonary and Critical Care, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA.
概括
单细胞转录组学揭示了囊性纤维化鼻上皮质中细胞类型特定的基因表达变化,突出显示了组织异质性. 这种方法补充了大量的RNA测序,以更深入地了解CF疾病机制.
科学领域:
- 呼吸系统医学 呼吸系统医学
- 基因组学就是基因组学.
- 细胞生物学 细胞生物学
背景情况:
- 鼻上皮质 (NE) 作为囊性纤维化 (CF) 下呼吸道上皮质的模型.
- NE包括多种细胞类型,与疾病相关的变化可以是细胞类型特异的.
- 了解组织异质性对于准确研究CF至关重要.
研究的目的:
- 通过单细胞转录学研究CF鼻上皮的细胞类型特定基因表达和异质性.
- 为了比较CF患者 (PwCF) 和健康志愿者 (HV) 之间的细胞类型丰富度.
- 为了评估单细胞和大量RNA测序数据之间的细胞类型丰度的相关性.
主要方法:
- 单细胞RNA测序 (scRNAseq) 在来自PwCF和HVs的鼻腔切除样本上进行.
- 分析了差异性基因表达和细胞类型的丰富性.
- 从scRNAseq获得的细胞类型丰富度与对联大量RNA测序数据的解卷分析进行了比较.
主要成果:
- 在CF NE中确定了细胞类型特异性表达的基因,包括与无处不在和炎症相关的基因.
- 在CF的上皮细胞和巨细胞中,Chaperome表达被下调.
- 在PwCF和HV之间没有发现细胞类型丰度的显著差异,具有显著的个体间异质性.
- 从批量和单细胞RNA测序中估计的细胞类型丰度之间观察到可变的相关性.
结论:
- 在健康个体和PwCF中,NE表现出显著的细胞类型异质性.
- 单细胞转录组学为NE研究提供了有价值的见解,补充了NE研究的大量RNA测序.
- 在CF中小组表达的下调可能受到内源和外源因素的影响,可能与CFTR表达水平有关.
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