Spatial multi-omics at subcellular resolution via high-throughput in situ pairwise sequencing.
Nat Biomed Eng
; 8(7): 872-889, 2024 Jul.
Article
in En
| MEDLINE
| ID: mdl-38745110
ABSTRACT
Technology for spatial multi-omics aids the discovery of new insights into cellular functions and disease mechanisms. Here we report the development and applicability of multi-omics in situ pairwise sequencing (MiP-seq), a method for the simultaneous detection of DNAs, RNAs, proteins and biomolecules at subcellular resolution. Compared with other in situ sequencing methods, MiP-seq enhances decoding capacity and reduces sequencing and imaging costs while maintaining the efficacy of detection of gene mutations, allele-specific expression and RNA modifications. MiP-seq can be integrated with in vivo calcium imaging and Raman imaging, which enabled us to generate a spatial multi-omics atlas of mouse brain tissues and to correlate gene expression with neuronal activity and cellular biochemical fingerprints. We also report a sequential dilution strategy for resolving optically crowded signals during in situ sequencing. High-throughput in situ pairwise sequencing may facilitate the multidimensional analysis of molecular and functional maps of tissues.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
High-Throughput Nucleotide Sequencing
Limits:
Animals
Language:
En
Journal:
Nat Biomed Eng
Year:
2024
Document type:
Article
Affiliation country:
China
Country of publication:
Reino Unido