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Decoder-seq enhances mRNA capture efficiency in spatial RNA sequencing

delete2024-01-16
delete10
PRE
AI
J
Jiao Cao
Z
Zhong Zheng
孙
孙迪 (Di Sun)
陈馨 封面图
陈馨 (Xin Chen)
R
Rui Cheng
L
Lv, Tianpeng
A
An Yu
J
Junhua Zheng
宋
宋佳 (Jia Song)
L
Lingling Wu
C
Chaoyong Yang *
DOI:10.1038/s41587-023-02086-ydelete
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摘要

摘要

En 中文
Spatial transcriptomics technologies with high resolution often lack high sensitivity in mRNA detection. Here we report a dendrimeric DNA coordinate barcoding design for spatial RNA sequencing (Decoder-seq), which offers both high sensitivity and high resolution. Decoder-seq combines dendrimeric nanosubstrates with microfluidic coordinate barcoding to generate spatial arrays with a DNA density approximately ten times higher than previously reported methods while maintaining flexibility in resolution. We show that the high RNA capture efficiency of Decoder-seq improved the detection of lowly expressed olfactory receptor (Olfr) genes in mouse olfactory bulbs and contributed to the discovery of a unique layer enrichment pattern for two Olfr genes. The near-cellular resolution provided by Decoder-seq has enabled the construction of a spatial single-cell atlas of the mouse hippocampus, revealing dendrite-enriched mRNAs in neurons. When applying Decoder-seq to human renal cell carcinomas, we dissected the heterogeneous tumor microenvironment across different cancer subtypes and identified spatial gradient-expressed genes related to epithelial-mesenchymal transition with the potential to predict tumor prognosis and progression. A spatial transcriptomics method achieves high gene detection sensitivity and flexible resolution.

期刊

Nature Biotechnology 封面图
Nature Biotechnology
IF:
41.7
论文数:
1.2W
被引数:
10.1W

机构

S
shanghai jiao tong university
学者数:
15.7W
论文数: 11.7W
被引数: 159
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