The emerging landscape of spatial profiling technologies
Abstract
Improved scale, multiplexing and resolution are establishing spatial nucleic acid and protein profiling methods as a major pillar for cellular atlas building of complex samples, from tissues to full organisms. Emerging methods yield omics measurements at resolutions covering the nano- to microscale, enabling the charting of cellular heterogeneity, complex tissue architectures and dynamic changes during development and disease. We present an overview of the developing landscape of in situ spatial genome, transcriptome and proteome technologies, exemplify their impact on cell biology and translational research, and discuss current challenges for their community-wide adoption. Among many transformative applications, we envision that spatial methods will map entire organs and enable next-generation pathology.
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ST enables the investigation of biological patterns that might otherwise be hidden in other -omics technologies, such as scRNA-seq or bulk RNA-seq.
“ST enables the investigation of biological patterns that might otherwise be hidden in other -omics technologies, such as scRNA-seq or bulk RNA-seq.26,27”
From hdWGCNA identifies co-expression networks in high-dimensional transcriptomics data (2023) · cites this paper as [27]
Cites
Visualization and analysis of gene expression in tissue sections by spatial transcriptomics
Ståhl, P. L., Salmén, F., Vickovic, S., Lundmark, A., Navarro, J. F., Magnusson, J., Giacomello, S., Asp, M., Westholm, J. O., Huss, M., et al. (2016) · Science · doi:10.1126/science.aaf2403 · Cited by 3,834 · see citing works
Accurate whole human genome sequencing using reversible terminator chemistry
Bentley, D. R., Balasubramanian, S., Swerdlow, H. P., Smith, G. P., Milton, J., Brown, C. G., Hall, K. P., Evers, D. J., Barnes, C. L., Bignell, H. R., et al. (2008) · Nature · doi:10.1038/nature07517 · Cited by 3,684 · see citing works
Regev, A., Teichmann, S. A., Lander, E. S., Amit, I., Benoist, C., Birney, E., Bodenmiller, B., Campbell, P., Carninci, P., Clatworthy, M., et al. (2017) · eLife · doi:10.7554/elife.27041 · Cited by 2,232 · see citing works
Self-citationImaging individual mRNA molecules using multiple singly labeled probes
Raj, A., van den Bogaard, P., Rifkin, S. A., van Oudenaarden, A., & Tyagi, S. (2008) · Nature Methods · doi:10.1038/nmeth.1253 · Cited by 2,028 · see citing works
Spatiotemporal transcriptomic atlas of mouse organogenesis using DNA nanoball-patterned arrays
Chen, A., Liao, S., Cheng, M., Ma, K., Wu, L., Lai, Y., Qiu, X., Yang, J., Xu, J., Hao, S., et al. (2022) · Cell · doi:10.1016/j.cell.2022.04.003 · Cited by 1,784 · see citing works
Three-dimensional intact-tissue sequencing of single-cell transcriptional states
Wang, X., Allen, W. E., Wright, M. A., Sylwestrak, E. L., Samusik, N., Vesuna, S., Evans, K., Liu, C., Ramakrishnan, C., Liu, J., et al. (2018) · Science · doi:10.1126/science.aat5691 · Cited by 1,620 · see citing works
Deep profiling of mouse splenic architecture with CODEX multiplexed imaging
Goltsev, Y., Samusik, N., Kennedy-Darling, J., Bhate, S., Hale, M., Vazquez, G., Black, S., & Nolan, G. P. (2018) · Cell · doi:10.1016/j.cell.2018.07.010 · Cited by 1,501 · see citing works
Comparative Analysis of Single-Cell RNA Sequencing Methods
Ziegenhain, C., Vieth, B., Parekh, S., Reinius, B., Guillaumet-Adkins, A., Smets, M., Leonhardt, H., Heyn, H., Hellmann, I., & Enard, W. (2017) · Molecular Cell · doi:10.1016/j.molcel.2017.01.023 · Cited by 1,494 · see citing works
Self-citationHighly sensitive spatial transcriptomics at near-cellular resolution with Slide-seqV2
Stickels, R. R., Murray, E., Kumar, P., Li, J., Marshall, J. L., Di Bella, D. J., Arlotta, P., Macosko, E. Z., & Chen, F. (2021) · Nature Biotechnology · doi:10.1038/s41587-020-0739-1 · Cited by 1,295 · see citing works
Sun, R., Limkin, E. J., Vakalopoulou, M., Dercle, L., Champiat, S., Han, S. R., Verlingue, L., Brandao, D., Lancia, A., Ammari, S., et al. (2018) · The Lancet Oncology · doi:10.1016/s1470-2045(18)30413-3 · Cited by 1,236 · see citing works
Rare cell variability and drug-induced reprogramming as a mode of cancer drug resistance
Shaffer, S. M., Dunagin, M. C., Torborg, S. R., Torre, E. A., Emert, B., Krepler, C., Beqiri, M., Sproesser, K., Brafford, P. A., Xiao, M., et al. (2017) · Nature · doi:10.1038/nature22794 · Cited by 1,218 · see citing works
Human Genome Sequencing Using Unchained Base Reads on Self-Assembling DNA Nanoarrays
Drmanac, R., Sparks, A. B., Callow, M. J., Halpern, A. L., Burns, N. L., Kermani, B. G., Carnevali, P., Nazarenko, I., Nilsen, G. B., Yeung, G., et al. (2010) · Science · doi:10.1126/science.1181498 · Cited by 1,212 · see citing works
Keren, L., Bosse, M., Marquez, D., Angoshtari, R., Jain, S., Varma, S., Yang, S.-R., Kurian, A., Van Valen, D., West, R., et al. (2018) · Cell · doi:10.1016/j.cell.2018.08.039 · Cited by 1,183 · see citing works
Multimodal Analysis of Composition and Spatial Architecture in Human Squamous Cell Carcinoma
Ji, A. L., Rubin, A. J., Thrane, K., Jiang, S., Reynolds, D. L., Meyers, R. M., Guo, M. G., George, B. M., Mollbrink, A., Bergenstråhle, J., et al. (2020) · Cell · doi:10.1016/j.cell.2020.05.039 · Cited by 1,117 · see citing works
Integrating single-cell and spatial transcriptomics to elucidate intercellular tissue dynamics
Longo, S. K., Guo, M. G., Ji, A. L., & Khavari, P. A. (2021) · Nature Reviews Genetics · doi:10.1038/s41576-021-00370-8 · Cited by 1,059 · see citing works
Spatial Transcriptomics and In Situ Sequencing to Study Alzheimer’s Disease
Chen, W.-T., Lu, A., Craessaerts, K., Pavie, B., Sala Frigerio, C., Corthout, N., Qian, X., Laláková, J., Kühnemund, M., Voytyuk, I., et al. (2020) · Cell · doi:10.1016/j.cell.2020.06.038 · Cited by 949 · see citing works
In situ sequencing for RNA analysis in preserved tissue and cells
Ke, R., Mignardi, M., Pacureanu, A., Svedlund, J., Botling, J., Wählby, C., & Nilsson, M. (2013) · Nature Methods · doi:10.1038/nmeth.2563 · Cited by 934 · see citing works
Highly multiplexed <i>in situ</i> protein imaging with signal amplification by Immuno-SABER
Saka, S. K., Wang, Y., Kishi, J. Y., Zhu, A., Zeng, Y., Xie, W., Kirli, K., Yapp, C., Cicconet, M., Beliveau, B. J., et al. (2018) · doi:10.1101/507566 · Cited by 485 · see citing works
Visualizing DNA folding and RNA in embryos at single-cell resolution
Mateo, L. J., Murphy, S. E., Hafner, A., Cinquini, I. S., Walker, C. A., & Boettiger, A. N. (2019) · Nature · doi:10.1038/s41586-019-1035-4 · Cited by 446 · see citing works
Massively multiplex chemical transcriptomics at single-cell resolution
Srivatsan, S. R., McFaline-Figueroa, J. L., Ramani, V., Saunders, L., Cao, J., Packer, J., Pliner, H. A., Jackson, D. L., Daza, R. M., Christiansen, L., et al. (2020) · Science · doi:10.1126/science.aax6234 · Cited by 401 · see citing works
Spatial-CUT&Tag: Spatially resolved chromatin modification profiling at the cellular level
Deng, Y., Bartosovic, M., Kukanja, P., Zhang, D., Liu, Y., Su, G., Enninful, A., Bai, Z., Castelo-Branco, G., & Fan, R. (2022) · Science · doi:10.1126/science.abg7216 · Cited by 393 · see citing works
Optical Pooled Screens in Human Cells
Feldman, D., Singh, A., Schmid-Burgk, J. L., Carlson, R. J., Mezger, A., Garrity, A. J., Zhang, F., & Blainey, P. C. (2019) · Cell · doi:10.1016/j.cell.2019.09.016 · Cited by 321 · see citing works
Transcriptome in vivo analysis (TIVA) of spatially defined single cells in live tissue
Lovatt, D., Ruble, B. K., Lee, J., Dueck, H., Kim, T. K., Fisher, S., Francis, C., Spaethling, J. M., Wolf, J. A., Grady, M. S., et al. (2014) · Nature Methods · doi:10.1038/nmeth.2804 · Cited by 287 · see citing works
Multimodal analysis of cell types in a hypothalamic node controlling social behavior
Kim, D.-W., Yao, Z., Graybuck, L. T., Kim, T. K., Nguyen, T. N., Smith, K. A., Fong, O., Yi, L., Koulena, N., Pierson, N., et al. (2019) · Cell · doi:10.1016/j.cell.2019.09.020 · Cited by 259 · see citing works
Cardozo Gizzi, A. M., Cattoni, D. I., Fiche, J.-B., Espinola, S. M., Gurgo, J., Messina, O., Houbron, C., Ogiyama, Y., Papadopoulos, G. L., Cavalli, G., et al. (2019) · Molecular Cell · doi:10.1016/j.molcel.2019.01.011 · Cited by 258 · see citing works
Imaging-based pooled CRISPR screening reveals regulators of lncRNA localization
Wang, C., Lu, T., Emanuel, G., Babcock, H. P., & Zhuang, X. (2019) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1903808116 · Cited by 111 · see citing works
Profiling the transcriptome with RNA SPOTs
Eng, C.-H. L., Shah, S., Thomassie, J., & Cai, L. (2017) · Nature Methods · doi:10.1038/nmeth.4500 · Cited by 105 · see citing works
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Methods and applications for single-cell and spatial multi-omics
Vandereyken, K., Sifrim, A., Thienpont, B., & Voet, T. (2023) · Nature Reviews Genetics · doi:10.1038/s41576-023-00580-2 · Cited by 1,244 · see citing works
hdWGCNA identifies co-expression networks in high-dimensional transcriptomics data
Morabito, S., Reese, F., Rahimzadeh, N., Miyoshi, E., & Swarup, V. (2023) · Cell Reports Methods · doi:10.1016/j.crmeth.2023.100498 · Cited by 773 · see citing works
How to build the virtual cell with artificial intelligence: Priorities and opportunities
Bunne, C., Roohani, Y., Rosen, Y., Gupta, A., Zhang, X., Roed, M., Alexandrov, T., AlQuraishi, M., Brennan, P., Burkhardt, D. B., et al. (2024) · Cell · doi:10.1016/j.cell.2024.11.015 · Cited by 393 · see citing works
“…imaging technologies, 65,100,101 including live-cell, and newer structural imaging technologies, such as cryoelectron tomography and soft X-ray tomography, 66,102,103 as well as novel spatial omics technologies, 104,105 offer opportunities to model biomolecules and functions across scales.”
Self-citationLIANA+ Provides an All-in-One Framework for Cell–Cell Communication Inference
Dimitrov, D., Schäfer, P. S. L., Farr, E., Rodriguez-Mier, P., Lobentanzer, S., Badia-i-Mompel, P., Dugourd, A., Tanevski, J., Ramirez Flores, R. O., & Saez-Rodriguez, J. (2024) · Nature Cell Biology · doi:10.1038/s41556-024-01469-w · Cited by 263 · see citing works
Impact of the Human Cell Atlas on medicine
Rood, J. E., Maartens, A., Hupalowska, A., Teichmann, S. A., & Regev, A. (2022) · Nature Medicine · doi:10.1038/s41591-022-02104-7 · Cited by 222 · see citing works
Spatial transcriptomics: Technologies, applications and experimental considerations
Wang, Y., Liu, B., Zhao, G., Lee, Y., Buzdin, A., Mu, X., Zhao, J., Chen, H., & Li, X. (2023) · Genomics · doi:10.1016/j.ygeno.2023.110671 · Cited by 218 · see citing works
Fan, J., Lu, F., Qin, T., Peng, W., Zhuang, X., Li, Y., Hou, X., Fang, Z., Yang, Y., Guo, E., et al. (2023) · Nature Genetics · doi:10.1038/s41588-023-01570-0 · Cited by 93 · see citing works
Decoder-seq enhances mRNA capture efficiency in spatial RNA sequencing
Cao, J., Zheng, Z., Sun, D., Chen, X., Cheng, R., Lv, T., An, Y., Zheng, J., Song, J., Wu, L., et al. (2024) · Nature Biotechnology · doi:10.1038/s41587-023-02086-y · Cited by 71 · see citing works
Bhattacherjee, A., Zhang, C., Watson, B. R., Djekidel, M. N., Moffitt, J. R., & Zhang, Y. (2023) · Nature Neuroscience · doi:10.1038/s41593-023-01455-9 · Cited by 71 · see citing works
Self-citationMultiplexed, image-based pooled screens in primary cells and tissues with PerturbView
Kudo, T., Meireles, A. M., Moncada, R., Chen, Y., Wu, P., Gould, J., Hu, X., Kornfeld, O., Jesudason, R., Foo, C., et al. (2025) · Nature Biotechnology · doi:10.1038/s41587-024-02391-0 · Cited by 74 · see citing works
Multiplexed spatial transcriptomics methods and the application of expansion microscopy
Fortner, A., & Bucur, O. (2024) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2024.1378875 · Cited by 10 · see citing works
Uncovering the signatures of aging and senescence in the human dorsolateral prefrontal cortex
Sloan, N. X., Mares, J., Daly, A. C., Grier, S., Haq, I., Jackson, C. A., Barretto, N., Casel, O., Kang, K., Khiste, S., et al. (2026) · Cell Genomics · doi:10.1016/j.xgen.2025.101127 · Cited by 2 · see citing works
“To build a transcriptomic map of aging and senescence (Figure 1A), we performed Visium spatial transcriptomics 40,41 (ST) and single-nucleus RNA sequencing (snRNA-seq) on donor tissues throughout our assembled cohort.”
- Authors
- Moffitt, J. R., Lundberg, E., & Heyn, H.
- Affiliations
- Boston Children's Hospital (US)
- Science for Life Laboratory (SE)
- Universitat Pompeu Fabra (ES)
- Corresponding author
- Heyn, Holger
- Venue
- Nature Reviews Genetics
- Published
- 2022-07-20
- Volume
- 23
- Issue
- 12
- Pages
- 741-759
- ISSN
- 1471-0056 (ISSN-L)
- 1471-0064
- OpenAlex
- W4286005528
- Cited by
- 419
- References
- 27
- Citations by year
- 2026: 93 · 2025: 107 · 2024: 108 · 2023: 96 · 2022: 15
- FWCI
- 8.62
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Nature Reviews Genetics (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Cancer Institute (R21CA249728)
- National Institute of General Medical Sciences (R01GM143277)
- National Institute of Diabetes and Digestive and Kidney Diseases (U01DK120447)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Single-cell and spatial transcriptomics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Phylogenetic Studies
- Keywords
- spatial omics, spatial transcriptomics, spatial genomics, spatial proteomics, cellular heterogeneity, tissue structure
- MeSH terms
- Genome, Proteome, Gene Expression Profiling, Single-Cell Analysis, Transcriptome
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