美團(tuán)隊(duì)利用微陣列空間轉(zhuǎn)錄組與單細(xì)胞測(cè)序揭示胰腺癌結(jié)構(gòu)
2020-01-16
來(lái)源:小柯機(jī)器人
美國(guó)紐約大學(xué)Itai Yanai團(tuán)隊(duì)利用基于微陣列的空間轉(zhuǎn)錄組學(xué)和單細(xì)胞RNA測(cè)序(scRNA-seq)揭示了胰腺導(dǎo)管腺癌的組織結(jié)構(gòu)。2020年1月13日,《自然—生物技術(shù)》雜志在線發(fā)表了這項(xiàng)成果。
研究人員結(jié)合了基于微陣列的空間轉(zhuǎn)錄組學(xué)方法,該方法使用一系列斑點(diǎn)揭示了基因表達(dá)的空間模式,每個(gè)斑點(diǎn)都捕獲了多個(gè)相鄰細(xì)胞的轉(zhuǎn)錄組,并從同一樣品中生成了scRNA-Seq。為了注釋不同組織區(qū)域的精準(zhǔn)細(xì)胞組成,研究人員報(bào)道了一種用于多峰相交分析的方法。將多模式相交分析應(yīng)用于原發(fā)性胰腺腫瘤,研究人員發(fā)現(xiàn)導(dǎo)管細(xì)胞、巨噬細(xì)胞、樹突狀細(xì)胞和癌細(xì)胞的亞群具有空間受限的富集,以及與其他細(xì)胞類型的獨(dú)特共富集。此外,研究人員確定表達(dá)壓力反應(yīng)基因模塊的炎癥成纖維細(xì)胞和癌細(xì)胞的共定位。這一用于繪制scRNA-seq定義的亞群結(jié)構(gòu)的方法可用于揭示復(fù)雜組織固有的相互作用。
據(jù)了解,scRNA-seq可以系統(tǒng)地識(shí)別組織中的細(xì)胞群,但是表征其空間組織仍然具有挑戰(zhàn)性。
附:英文原文
Title: Integrating microarray-based spatial transcriptomics and single-cell RNA-seq reveals tissue architecture in pancreatic ductal adenocarcinomas
Author: Reuben Moncada, Dalia Barkley, Florian Wagner, Marta Chiodin, Joseph C. Devlin, Maayan Baron, Cristina H. Hajdu, Diane M. Simeone, Itai Yanai
Issue&Volume: 2020-01-13
Abstract: Single-cell RNA sequencing (scRNA-seq) enables the systematic identification of cell populations in a tissue, but characterizing their spatial organization remains challenging. We combine a microarray-based spatial transcriptomics method that reveals spatial patterns of gene expression using an array of spots, each capturing the transcriptomes of multiple adjacent cells, with scRNA-Seq generated from the same sample. To annotate the precise cellular composition of distinct tissue regions, we introduce a method for multimodal intersection analysis. Applying multimodal intersection analysis to primary pancreatic tumors, we find that subpopulations of ductal cells, macrophages, dendritic cells and cancer cells have spatially restricted enrichments, as well as distinct coenrichments with other cell types. Furthermore, we identify colocalization of inflammatory fibroblasts and cancer cells expressing a stress-response gene module. Our approach for mapping the architecture of scRNA-seq-defined subpopulations can be applied to reveal the interactions inherent to complex tissues.
DOI: 10.1038/s41587-019-0392-8
Source: https://www.nature.com/articles/s41587-019-0392-8
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