ArticleProceedings of the National Academy of Sciences of the United States of America2019
Spatial transcriptome profiling by MERFISH reveals subcellular RNA compartmentalization and cell cycle-dependent gene expression.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 476 papers, 2 of them syntheses that pooled it.
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476 citing papers in PubMed, 2 syntheses or guidelines pooled it, 796 citations in OpenAlex.
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- 3D multi-omics tumour atlases: from technology to biology and clinical translation.Nature reviews. Cancer · 2026Review
- Unveiling the role of spatial transcriptomics in the analysis of the tumor immune microenvironment (Review).International journal of molecular medicine · 2026Review
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- Longitudinal live-cell chemical imaging using coherent Raman scattering microscopy.The Analyst · 2026Review
- RNA-aware tissue preservation workflows for high-quality spatial transcriptomics.bioRxiv : the preprint server for biology · 2026Article
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- Directed evolution of Lantern enables rapid RNA and protein proximity labeling.Nature chemical biology · 2026Article
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- Integration of imaging-based and sequencing-based spatial omics mapping on the same tissue section via DBiTplus.Nature methods · 2026Article
- Immune niches in brain tumors: glial-immune cell interactions and spatial microdomains.Acta neuropathologica communications · 2026Review
- Spatial ecotype in tumor immune exclusion: from spatial architecture to therapeutic strategies.Molecular cancer · 2026Review
- Spatial Immune Coding in Tumor-Draining Lymph Nodes: Functional Compartmentalization of Immune Activation and Immunosuppression.International journal of molecular sciences · 2026Review
- Uncovering ectopic GC-like niches for tumor reactive lymphocyte priming in lung adenocarcinoma using Stereo-XCR-seq.Nature communications · 2026Article
416 more citing papers are in PubMed but not listed here.
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
The expression profiles and spatial distributions of RNAs regulate many cellular functions. Image-based transcriptomic approaches provide powerful means to measure both expression and spatial information of RNAs in individual cells within their native environment. Among these approaches, multiplexed error-robust fluorescence in situ hybridization (MERFISH) has achieved spatially resolved RNA quantification at transcriptome scale by massively multiplexing single-molecule FISH measurements. Here, we increased the gene throughput of MERFISH and demonstrated simultaneous measurements of RNA transcripts from ∼10,000 genes in individual cells with ∼80% detection efficiency and ∼4% misidentification rate. We combined MERFISH with cellular structure imaging to determine subcellular compartmentalization of RNAs. We validated this approach by showing enrichment of secretome transcripts at the endoplasmic reticulum, and further revealed enrichment of long noncoding RNAs, RNAs with retained introns, and a subgroup of protein-coding mRNAs in the cell nucleus. Leveraging spatially resolved RNA profiling, we developed an approach to determine RNA velocity in situ using the balance of nuclear versus cytoplasmic RNA counts. We applied this approach to infer pseudotime ordering of cells and identified cells at different cell-cycle states, revealing ∼1,600 genes with putative cell cycle-dependent expression and a gradual transcription profile change as cells progress through cell-cycle stages. Our analysis further revealed cell cycle-dependent and cell cycle-independent spatial heterogeneity of transcriptionally distinct cells. We envision that the ability to perform spatially resolved, genome-wide RNA profiling with high detection efficiency and accuracy by MERFISH could help address a wide array of questions ranging from the regulation of gene expression in cells to the development of cell fate and organization in tissues.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.