Cited by 2,969Single-cell and spatial transcriptomicsRNA Research and SplicingAdvanced Fluorescence Microscopy Techniques

Spatially resolved, highly multiplexed RNA profiling in single cells

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Chen, Kok Hao, Boettiger, Alistair N., Moffitt, Jeffrey R., Wang, Siyuan, Zhuang, Xiaowei·2015·Science

Abstract

Multiplexed RNA imaging in single cells: The basis of cellular function is where and when proteins are expressed and in what quantities. Single-molecule fluorescence in situ hybridization (smFISH) experiments quantify the copy number and location of mRNA molecules; however, the numbers of RNA species that can be simultaneously measured by smFISH has been limited. Using combinatorial labeling with error-robust encoding schemes, Chen et al. simultaneously imaged 100 to 1000 RNA species in a single cell. Such large-scale detection allows regulatory interactions to be analyzed at the transcriptome scale. Science , this issue p. 10.1126/science.aaa6090

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  • Cellular identity and function are governed by elaborate regulatory circuits, many of which act through control of RNA expression.

    “Cellular identity and function are governed by elaborate regulatory circuits, many of which act through control of RNA expression166,167.”
  • merFISH and seqFISH use sequencing-by-hybridisation techniques for transcriptomic quantification.

    “The recently developed methods of merFISH (Chen et al, 2015) and seqFISH (Shah et al, 2016b) use sequencing‐by‐hybridisation techniques for transcriptomic quantification.”
  • MERFISH increased the number of RNA molecules simultaneously imaged in single cells using combinatorial labelling and sequential imaging.

    “A year later, MERFISH substantially increased the number of RNA molecules that could be simultaneously imaged in single cells by utilizing combinatorial labelling and sequential imaging of multiple readout hybridizations101.”

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Authors
Chen, K. H., Boettiger, A. N., Moffitt, J. R., Wang, S., & Zhuang, X.
Affiliations
Howard Hughes Medical Institute (US)
Corresponding author
  • Chen, Kok Hao
  • Boettiger, Alistair N.
  • Moffitt, Jeffrey R.
  • Zhuang, Xiaowei
Venue
Science
Published
2015-04-24
Volume
348
Issue
6233
Pages
aaa6090-aaa6090
ISSN
  • 0036-8075 (ISSN-L)
  • 1095-9203
OpenAlex
W2042789810
Cited by
2,969
References
53
Citations by year
2026: 478 · 2025: 491 · 2024: 466 · 2023: 314 · 2022: 259 · 2021: 261 · 2020: 210 · 2019: 161 · 2018: 128 · 2017: 95 · 2016: 69 · 2015: 33 · 2014: 2 · 2012: 1
FWCI
47.21
Type
journal article
Language
en
Open access
Locations
  • Science (publishedVersion)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
  • Digital Access to Scholarship at Harvard (DASH) (Harvard University) (submittedVersion, cc-by)
Funders
  • National Institutes of Health
  • Howard Hughes Medical Institute
  • Damon Runyon Foundation
  • Helen Hay Whitney Foundation
  • Agency for Science, Technology and Research of Singapore
  • Jane Coffins Child Foundation
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Single-cell and spatial transcriptomics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Research and Splicing
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Biophysics › Advanced Fluorescence Microscopy Techniques
Keywords
MERFISH, spatial transcriptomics, gene regulatory networks, single-molecule imaging
MeSH terms
Fibroblasts, Humans, RNA, Messenger, RNA Probes, In Situ Hybridization, Fluorescence, Gene Expression Profiling, Molecular Imaging, High-Throughput Screening Assays, Single-Cell Analysis, Transcriptome

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