关键词: Colocalization analysis Formalin-fixed paraffin-embedded (FFPE) tissues Host–pathogen interactions Spatial transcriptomics

Mesh : Humans Transcriptome Tissue Fixation Formaldehyde COVID-19 SARS-CoV-2

来  源:   DOI:10.1186/s13059-023-03080-y   PDF(Pubmed)

Abstract:
Technologies to study localized host-pathogen interactions are urgently needed. Here, we present a spatial transcriptomics approach to simultaneously capture host and pathogen transcriptome-wide spatial gene expression information from human formalin-fixed paraffin-embedded (FFPE) tissue sections at a near single-cell resolution. We demonstrate this methodology in lung samples from COVID-19 patients and validate our spatial detection of SARS-CoV-2 against RNAScope and in situ sequencing. Host-pathogen colocalization analysis identified putative modulators of SARS-CoV-2 infection in human lung cells. Our approach provides new insights into host response to pathogen infection through the simultaneous, unbiased detection of two transcriptomes in FFPE samples.
摘要:
迫切需要研究局部宿主-病原体相互作用的技术。这里,我们提出了一种空间转录组学方法,可以从人福尔马林固定的石蜡包埋(FFPE)组织切片中以近单细胞分辨率同时捕获宿主和病原体转录组范围的空间基因表达信息。我们在COVID-19患者的肺样本中证明了这种方法,并验证了我们针对RNAScope的SARS-CoV-2的空间检测和原位测序。宿主-病原体共定位分析确定了人肺细胞中SARS-CoV-2感染的推定调节剂。我们的方法为宿主对病原体感染的反应提供了新的见解,FFPE样品中两个转录组的无偏检测。
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