Rapid and signal crowdedness-robust in situ sequencing through hybrid block coding.
Tianyi ChangWuji HanMengcheng JiangJizhou LiZhizhao LiaoMingchuan TangJianyun ZhangJie ShenZitian ChenPeng FeiXianwen RenYuhong PangGuanbo WangJianbian WangYanyi HuangPublished in: Proceedings of the National Academy of Sciences of the United States of America (2023)
Spatial transcriptomics technology has revolutionized our understanding of cell types and tissue organization, opening possibilities for researchers to explore transcript distributions at subcellular levels. However, existing methods have limitations in resolution, sensitivity, or speed. To overcome these challenges, we introduce SPRINTseq (Spatially Resolved and signal-diluted Next-generation Targeted sequencing), an innovative in situ sequencing strategy that combines hybrid block coding and molecular dilution strategies. Our method enables fast and sensitive high-resolution data acquisition, as demonstrated by recovering over 142 million transcripts using a 108-gene panel from 453,843 cells from four mouse brain coronal slices in less than 2 d. Using this advanced technology, we uncover the cellular and subcellular molecular architecture of Alzheimer's disease, providing additional information into abnormal cellular behaviors and their subcellular mRNA distribution. This improved spatial transcriptomics technology holds great promise for exploring complex biological processes and disease mechanisms.
Keyphrases
- single cell
- rna seq
- high resolution
- single molecule
- big data
- healthcare
- stem cells
- gene expression
- cognitive decline
- electronic health record
- mass spectrometry
- cancer therapy
- liquid chromatography tandem mass spectrometry
- dna methylation
- liquid chromatography
- deep learning
- health information
- cell therapy
- drug delivery
- bone marrow
- gas chromatography
- tandem mass spectrometry