Decoder-seq enhances mRNA capture efficiency in spatial RNA sequencing

© 2024. The Author(s), under exclusive licence to Springer Nature America, Inc..

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.

Medienart:

E-Artikel

Erscheinungsjahr:

2024

Erschienen:

2024

Enthalten in:

Zur Gesamtaufnahme - year:2024

Enthalten in:

Nature biotechnology - (2024) vom: 16. Jan.

Sprache:

Englisch

Beteiligte Personen:

Cao, Jiao [VerfasserIn]
Zheng, Zhong [VerfasserIn]
Sun, Di [VerfasserIn]
Chen, Xin [VerfasserIn]
Cheng, Rui [VerfasserIn]
Lv, Tianpeng [VerfasserIn]
An, Yu [VerfasserIn]
Zheng, Junhua [VerfasserIn]
Song, Jia [VerfasserIn]
Wu, Lingling [VerfasserIn]
Yang, Chaoyong [VerfasserIn]

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Date Revised 16.01.2024

published: Print-Electronic

Citation Status Publisher

doi:

10.1038/s41587-023-02086-y

funding:

Förderinstitution / Projekttitel:

PPN (Katalog-ID):

NLM367193302