ArticleDevelopment (Cambridge, England)2016
Single-molecule RNA detection at depth by hybridization chain reaction and tissue hydrogel embedding and clearing.
Article in Development (Cambridge, England), 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 124 papers, 1 of them a synthesis that pooled it.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
124 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Reference-based cell type matching of in situ image-based spatial transcriptomics data on primary visual cortex of mouse brain.Scientific reports · 2023Pooled it
- Immunophenotyping by Spatial Biology.Methods in molecular biology (Clifton, N.J.) · 2027Article
- Insights Into Spatial Transcriptomics: Exploring Recent Technical Developments and Their Diverse Applications.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2026Review
- Artificial intelligence in spatial transcriptomics: a review of methods, datasets, and directions.Briefings in bioinformatics · 2026Review
- Spatial tissue analysis of secondary sarcoma following CAR T cell therapy for B cell lymphoma.iScience · 2026Article
- Computational analysis in spatial transcriptomics: methods and perspectives.Briefings in bioinformatics · 2026Review
- A Simple and Fast Optical Clearing Method for Whole-Mount Fluorescence In Situ Hybridization (FISH) Imaging.Journal of biophotonics · 2025Article
- Scalable spatial single-cell transcriptomics and translatomics in 3D thick tissue blocks.Nature methods · 2025Article
- Spatial Proofreading Amplification ofbioRxiv : the preprint server for biology · 2025Article
- DNA-PAINT Imaging with Hydrogel Imprinting and Clearing.ACS sensors · 2025Article
- Advances in spatial transcriptomics and its application in the musculoskeletal system.Bone research · 2025Review
- Advances and applications in single-cell and spatial genomics.Science China. Life sciences · 2025Review
- Transcriptional determinants of goal-directed learning and representational drift in the parahippocampal cortex.Cell reports · 2025Article
- Applications of Nanotechnology for Spatial Omics: Biological Structures and Functions at Nanoscale Resolution.ACS nano · 2025Review
- Detecting gene expression in Caenorhabditis elegans.Genetics · 2025Review
- NiCo identifies extrinsic drivers of cell state modulation by niche covariation analysis.Nature communications · 2024Article
- Next-generation spatial transcriptomics: unleashing the power to gear up translational oncology.MedComm · 2024Review
- Multiplex, Quantitative, High-Resolution Imaging of Protein:Protein Complexes via Hybridization Chain Reaction.ACS chemical biology · 2024Article
- HCR spectral imaging: 10-plex, quantitative, high-resolution RNA and protein imaging in highly autofluorescent samples.Development (Cambridge, England) · 2024Article
- Image-based 3D genomics through chromatin tracing.Nature reviews. Methods primers · 2024Article
64 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
11 authors.
Funding
Abstract
Accurate and robust detection of mRNA molecules in thick tissue samples can reveal gene expression patterns in single cells within their native environment. Preserving spatial relationships while accessing the transcriptome of selected cells is a crucial feature for advancing many biological areas - from developmental biology to neuroscience. However, because of the high autofluorescence background of many tissue samples, it is difficult to detect single-molecule fluorescence in situ hybridization (smFISH) signals robustly in opaque thick samples. Here, we draw on principles from the emerging discipline of dynamic nucleic acid nanotechnology to develop a robust method for multi-color, multi-RNA imaging in deep tissues using single-molecule hybridization chain reaction (smHCR). Using this approach, single transcripts can be imaged using epifluorescence, confocal or selective plane illumination microscopy (SPIM) depending on the imaging depth required. We show that smHCR has high sensitivity in detecting mRNAs in cell culture and whole-mount zebrafish embryos, and that combined with SPIM and PACT (passive CLARITY technique) tissue hydrogel embedding and clearing, smHCR can detect single mRNAs deep within thick (0.5 mm) brain slices. By simultaneously achieving ∼20-fold signal amplification and diffraction-limited spatial resolution, smHCR offers a robust and versatile approach for detecting single mRNAs in situ, including in thick tissues where high background undermines the performance of unamplified smFISH.
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Registered trials
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.