The DOI matches its Crossref record; 51 of the 53 references it cites were found in a registry or an index.
Spatial genomics enables multi-modal study of clonal heterogeneity in tissues
Open accessAbstract
The state and behaviour of a cell can be influenced by both genetic and environmental factors. In particular, tumour progression is determined by underlying genetic aberrations 1-4 as well as the makeup of the tumour microenvironment 5,6. Quantifying the contributions of these factors requires new technologies that can accurately measure the spatial location of genomic sequence together with phenotypic readouts. Here we developed slide-DNA-seq, a method for capturing spatially resolved DNA sequences from intact tissue sections. We demonstrate that this method accurately preserves local tumour architecture and enables the de novo discovery of distinct tumour clones and their copy number alterations. We then apply slide-DNA-seq to a mouse model of metastasis and a primary human cancer, revealing that clonal populations are confined to distinct spatial regions. Moreover, through integration with spatial transcriptomics, we uncover distinct sets of genes that are associated with clone-specific genetic aberrations, the local tumour microenvironment, or both. Together, this multi-modal spatial genomics approach provides a versatile platform for quantifying how cell-intrinsic and cell-extrinsic factors contribute to gene expression, protein abundance and other cellular phenotypes.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In the citing paper
“Very recently, a newly developed spatial technology, slide-DNA-seq, was used to preserve local tumour architecture, enabling the discovery of distinct tumour clones and their copy number variations157.”
From The technological landscape and applications of single-cell multi-omics (2023) · cites this paper as [157]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
1 retracted
HMGA2 functions as a competing endogenous RNA to promote lung cancer progression
Kumar, M. S., Armenteros-Monterroso, E., East, P., Chakravorty, P., Matthews, N., Winslow, M. M., & Downward, J. (2013) · Nature · doi:10.1038/nature12785 · Cited by 255
RetractedComprehensive molecular characterization of human colon and rectal cancer
The Cancer Genome Atlas Network (2012) · Nature · doi:10.1038/nature11252 · Cited by 8,499
Buenrostro, J. D., Giresi, P. G., Zaba, L. C., Chang, H. Y., & Greenleaf, W. J. (2013) · Nature Methods · doi:10.1038/nmeth.2688 · Cited by 6,422
Self-citationClonal heterogeneity and tumor evolution: past, present, and the future
McGranahan, N., & Swanton, C. (2017) · Cell · doi:10.1016/j.cell.2017.01.018 · Cited by 2,840
Slide-seq: A scalable technology for measuring genome-wide expression at high spatial resolution
Rodriques, S. G., Stickels, R. R., Goeva, A., Martin, C. A., Murray, E., Vanderburg, C. R., Welch, J., Chen, L. M., Chen, F., & Macosko, E. Z. (2019) · Science · doi:10.1126/science.aaw1219 · Cited by 2,424
Self-citationTracking the Evolution of Non–Small-Cell Lung Cancer
Jamal-Hanjani, M., Wilson, G. A., McGranahan, N., Birkbak, N. J., Watkins, T. B. K., Veeriah, S., Shafi, S., Johnson, D. H., Mitter, R., Rosenthal, R., et al. (2017) · New England Journal of Medicine · doi:10.1056/nejmoa1616288 · Cited by 2,349
Concepts of extracellular matrix remodelling in tumour progression and metastasis
Winkler, J., Abisoye-Ogunniyan, A., Metcalf, K. J., & Werb, Z. (2020) · Nature Communications · doi:10.1038/s41467-020-18794-x · Cited by 2,296
Robust decomposition of cell type mixtures in spatial transcriptomics
Cable, D. M., Murray, E., Zou, L. S., Goeva, A., Macosko, E. Z., Chen, F., & Irizarry, R. A. (2022) · Nature Biotechnology · doi:10.1038/s41587-021-00830-w · Cited by 1,487
Self-citationThe Integrative Human Microbiome Project
The Integrative HMP (iHMP) Research Network Consortium, Proctor, L. M., Creasy, H. H., Fettweis, J. M., Lloyd-Price, J., Mahurkar, A., Zhou, W., Buck, G. A., Snyder, M. P., Strauss, J. F., et al. (2019) · Nature · doi:10.1038/s41586-019-1238-8 · Cited by 1,381
Evolution and impact of subclonal mutations in chronic lymphocytic leukemia
Landau, D. A., Carter, S. L., Stojanov, P., McKenna, A., Stevenson, K., Lawrence, M. S., Sougnez, C., Stewart, C., Sivachenko, A., Wang, L., et al. (2013) · Cell · doi:10.1016/j.cell.2013.01.019 · Cited by 1,379
Highly 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
Self-citationThe updated landscape of tumor microenvironment and drug repurposing
Jin, M.-Z., & Jin, W.-L. (2020) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-020-00280-x · Cited by 1,262
Towards Practical, High-Capacity, Low-Maintenance Information Storage in Synthesized DNA
Goldman, N., Bertone, P., Chen, S., Dessimoz, C., LeProust, E. M., Sipos, B., & Birney, E. (2013) · Nature · doi:10.1038/nature11875 · Cited by 1,220
Somatic activation of the K-ras oncogene causes early onset lung cancer in mice
Johnson, L., Mercer, K., Greenbaum, D., Bronson, R. T., Crowley, D., Tuveson, D. A., & Jacks, T. (2001) · Nature · doi:10.1038/35074129 · Cited by 1,179
Self-citationConsensus molecular subtypes and the evolution of precision medicine in colorectal cancer
Dienstmann, R., Vermeulen, L., Guinney, J., Kopetz, S., Tejpar, S., & Tabernero, J. M. (2017) · Nature reviews. Cancer · doi:10.1038/nrc.2016.126 · Cited by 1,070
The evolutionary history of 2,658 cancers
Gerstung, M., Jolly, C., Leshchiner, I., Dentro, S. C., Gonzalez, S., Rosebrock, D., Mitchell, T. J., Rubanova, Y., Anur, P., Yu, K., et al. (2020) · Nature · doi:10.1038/s41586-019-1907-7 · Cited by 1,057
A Big Bang model of human colorectal tumor growth
Sottoriva, A., Kang, H., Ma, Z., Graham, T. A., Salomon, M. P., Zhao, J., Marjoram, P., Siegmund, K. D., Press, M. F., Shibata, D. K., et al. (2015) · Nature Genetics · doi:10.1038/ng.3214 · Cited by 1,037
Clonal evolution in breast cancer revealed by single nucleus genome sequencing
Wang, Y., Waters, J., Leung, M. L., Unruh, A., Roh, W., Shi, X., Chen, K., Scheet, P., Vattathil, S., Liang, H., et al. (2014) · Nature · doi:10.1038/nature13600 · Cited by 1,029
Turning Cold into Hot: Firing up the Tumor Microenvironment
Duan, Q., Zhang, H., Zheng, J., & Zhang, L. (2020) · Trends in Cancer · doi:10.1016/j.trecan.2020.02.022 · Cited by 934
Resolving genetic heterogeneity in cancer
Turajlic, S., Sottoriva, A., Graham, T. A., & Swanton, C. (2019) · Nature Reviews Genetics · doi:10.1038/s41576-019-0114-6 · Cited by 675
Single-Cell Exome Sequencing Reveals Single-Nucleotide Mutation Characteristics of a Kidney Tumor
Xu, X., Hou, Y., Yin, X., Bao, L., Tang, A., Song, L., Li, F., Tsang, S., Wu, K., Wu, H., et al. (2012) · Cell · doi:10.1016/j.cell.2012.02.025 · Cited by 667
Self-citationCircular ecDNA promotes accessible chromatin and high oncogene expression
Wu, S., Turner, K. M., Nguyen, N., Raviram, R., Erb, M. L., Santini, J., Luebeck, J., Rajkumar, U., Diao, Y., Li, B., et al. (2019) · Nature · doi:10.1038/s41586-019-1763-5 · Cited by 661
Mechanical compression drives cancer cells toward invasive phenotype
Tse, J. M., Cheng, G., Tyrrell, J. A., Wilcox-Adelman, S. A., Boucher, Y., Jain, R. K., & Munn, L. L. (2012) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1118910109 · Cited by 631
Stylianopoulos, T., Munn, L. L., & Jain, R. K. (2018) · Trends in cancer · doi:10.1016/j.trecan.2018.02.005 · Cited by 589
53BP1, a Mediator of the DNA Damage Checkpoint
Wang, B., Matsuoka, S., Carpenter, P. B., & Elledge, S. J. (2002) · Science · doi:10.1126/science.1076182 · Cited by 578
Adey, A., Morrison, H. G., Asan, Xu, X., Kitzman, J. O., Turner, E. H., Stackhouse, B., MacKenzie, A. P., Caruccio, N. C., Zhang, X., et al. (2010) · Genome biology · doi:10.1186/gb-2010-11-12-r119 · Cited by 566
Lineage Tracing in Humans Enabled by Mitochondrial Mutations and Single-Cell Genomics
Ludwig, L. S., Lareau, C. A., Ulirsch, J. C., Christian, E., Muus, C., Li, L. H., Pelka, K., Ge, W. H., Oren, Y., Brack, A., et al. (2019) · Cell · doi:10.1016/j.cell.2019.01.022 · Cited by 554
Self-citationClinical implications of intratumor heterogeneity: challenges and opportunities
y Cajal, S. R., Sesé, M., Capdevila, C., Aasen, T., Mattos‐Arruda, L. D., Díaz‐Cano, S. J., Hernández‐Losa, J., & Castellví, J. (2020) · Journal of Molecular Medicine · doi:10.1007/s00109-020-01874-2 · Cited by 549
Transforming growth factor-β employs HMGA2 to elicit epithelial–mesenchymal transition
Thuault, S., Valcourt, U., Petersen, M., Manfioletti, G., Heldin, C., & Moustakas, A. (2006) · The Journal of Cell Biology · doi:10.1083/jcb.200512110 · Cited by 500
Bisulfite-free direct detection of 5-methylcytosine and 5-hydroxymethylcytosine at base resolution
Liu, Y., Siejka-Zielińska, P., Velikova, G., Bi, Y., Yuan, F., Tomková, M., Bai, C., Chen, L., Schuster‐Böckler, B., & Song, C. (2019) · Nature Biotechnology · doi:10.1038/s41587-019-0041-2 · Cited by 480
Multiclonal Invasion in Breast Tumors Identified by Topographic Single Cell Sequencing
Casasent, A. K., Schalck, A., Gao, R., Sei, E., Long, A., Pangburn, W., Casasent, T., Meric-Bernstam, F., Edgerton, M. E., & Navin, N. E. (2018) · Cell · doi:10.1016/j.cell.2017.12.007 · Cited by 411
Divergent modes of clonal spread and intraperitoneal mixing in high-grade serous ovarian cancer
McPherson, A., Roth, A. J. L., Laks, E., Masud, T., Bashashati, A., Zhang, A. W., Ha, G., Biele, J., Yap, D., Wan, A., et al. (2016) · Nature Genetics · doi:10.1038/ng.3573 · Cited by 337
The delivery challenge: fulfilling the promise of therapeutic genome editing
van Haasteren, J., Li, J., Scheideler, O. J., Murthy, N., & Schaffer, D. V. (2020) · Nature Biotechnology · doi:10.1038/s41587-020-0565-5 · Cited by 285
Self-citationGenetic and Clonal Dissection of Murine Small Cell Lung Carcinoma Progression by Genome Sequencing
McFadden, D. G., Papagiannakopoulos, T. Y., Taylor-Weiner, A. N., Stewart, C., Carter, S. L., Cibulskis, K., Bhutkar, A. J., McKenna, A., Dooley, A. L., Vernon, A. N., et al. (2014) · Cell · doi:10.1016/j.cell.2014.02.031 · Cited by 284
Self-citationHMGA2 Is a Driver of Tumor Metastasis
Morishita, A., Zaidi, M. R., Mitoro, A., Sankarasharma, D., Szabolcs, M. J., Okada, Y., D'Armiento, J. M., & Chada, K. K. (2013) · Cancer Research · doi:10.1158/0008-5472.can-12-3848 · Cited by 257
Breast tumours maintain a reservoir of subclonal diversity during expansion
Minussi, D. C., Nicholson, M. D., Ye, H., Davis, A., Wang, K., Baker, T., Tarabichi, M., Sei, E., Du, H., Rabbani, M., et al. (2021) · Nature · doi:10.1038/s41586-021-03357-x · Cited by 256
Mechanism of RAD51-Dependent DNA Interstrand Cross-Link Repair
Long, D. T., Räschle, M., Joukov, V., & Walter, J. C. (2011) · Science · doi:10.1126/science.1204258 · Cited by 238
Brayer, K. J., Frerich, C. A., Kang, H., & Ness, S. A. (2015) · Cancer Discovery · doi:10.1158/2159-8290.cd-15-0859 · Cited by 225
Epigenomic State Transitions Characterize Tumor Progression in Mouse Lung Adenocarcinoma
LaFave, L. M., Kartha, V. K., Ma, S., Meli, K., Priore, I. S. D., Lareau, C. A., Naranjo, S., Westcott, P. M. K., Duarte, F. M., Sankar, V., et al. (2020) · Cancer Cell · doi:10.1016/j.ccell.2020.06.006 · Cited by 216
Self-citationFarhad, M. E., Rolig, A. S., & Redmond, W. L. (2018) · OncoImmunology · doi:10.1080/2162402x.2018.1434467 · Cited by 212
In situ genome sequencing resolves DNA sequence and structure in intact biological samples
Payne, A. C., Chiang, Z., Reginato, P., Mangiameli, S. M., Murray, E. M., Yao, C., Markoulaki, S., Earl, A., Labade, A. S., Jaenisch, R., et al. (2021) · Science · doi:10.1126/science.aay3446 · Cited by 199
Self-citationMCM7 amplification and overexpression are associated with prostate cancer progression
Ren, B., Yu, G., Tseng, G. C., Cieply, K. M., Gavel, T., Nelson, J., Michalopoulos, G. K., Yu, Y., & Luo, J.-H. (2005) · Oncogene · doi:10.1038/sj.onc.1209134 · Cited by 190
Erratum: Consensus molecular subtypes and the evolution of precision medicine in colorectal cancer
Dienstmann, R., Vermeulen, L., Guinney, J., Kopetz, S., Tejpar, S., & Tabernero, J. M. (2017) · Nature reviews. Cancer · doi:10.1038/nrc.2017.24 · Cited by 183
Plag1 and Plagl2 are oncogenes that induce acute myeloid leukemia in cooperation with Cbfb-MYH11
Landrette, S. F., Kuo, Y., Hensen, K., van Doorn-Khosrovani, S. B. V. W., Perrat, P. N., de Ven, W. J. M. V., Delwel, R., & Castilla, L. H. (2004) · Blood · doi:10.1182/blood-2004-09-3630 · Cited by 130
Ubiquitinated Fancd2 recruits Fan1 to stalled replication forks to prevent genome instability
Lachaud, C., Moreno, A., Marchesi, F., Toth, R. L., Blow, J. J., & Rouse, J. W. (2016) · Science · doi:10.1126/science.aad5634 · Cited by 119
Humphries, A., Cereser, B., Gay, L. J., Miller, D. S. J., Das, B., Gutteridge, A., Elia, G., Nye, E. L., Jeffery, R. E., Poulsom, R., et al. (2013) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1220353110 · Cited by 98
Selection of metastasis competent subclones in the tumour interior
Zhao, Y., Fu, X., Lopez, J. I., Rowan, A., Au, L., Fendler, A., Hazell, S., Xu, H., Horswell, S., Shepherd, S. T. C., et al. (2021) · Nature Ecology & Evolution · doi:10.1038/s41559-021-01456-6 · Cited by 95
Wu, C.-Y., Lau, B. T., Kim, H. S., Sathe, A., Grimes, S. M., Ji, H. P., & Zhang, N. R. (2021) · Nature Biotechnology · doi:10.1038/s41587-021-00911-w · Cited by 75
Harnessing Tumor Evolution to Circumvent Resistance
McNamara, K. L., & Curtis, C. N. (2018) · Trends in Genetics · doi:10.1016/j.tig.2018.05.007 · Cited by 70
Prom1 Function in Development, Intestinal Inflammation, and Intestinal Tumorigenesis
Karim, B. O., Rhee, K., Liu, G., Yun, K., & Brant, S. R. (2014) · Frontiers in Oncology · doi:10.3389/fonc.2014.00323 · Cited by 33
Many private mutations originate from the first few divisions of a human colorectal adenoma
Kang, H., Salomon, M. P., Sottoriva, A., Zhao, J., Toy, M., Press, M. F., Curtis, C. N., Marjoram, P., Siegmund, K. D., & Shibata, D. K. (2015) · The Journal of Pathology · doi:10.1002/path.4581 · Cited by 32
Cited by
Sorted by citations
The technological landscape and applications of single-cell multi-omics
Baysoy, A., Bai, Z., Satija, R., & Fan, R. (2023) · Nature Reviews Molecular Cell Biology · doi:10.1038/s41580-023-00615-w · Cited by 1,037
Breast cancer: pathogenesis and treatments
Xiong, X., Zheng, L., Ding, Y., Chen, Y., Cai, Y., Wang, L., Huang, L., Liu, C., Shao, Z., & Yu, K. (2025) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-024-02108-4 · Cited by 1,170
Spatially resolved multi-omics deciphers bidirectional tumor-host interdependence in glioblastoma
Ravi, V. M., Will, P., Kueckelhaus, J., Sun, N., Joseph, K., Salié, H., Vollmer, L., Kuliešiūtė, U., von Ehr, J., Benotmane, J. K., et al. (2022) · Cancer Cell · doi:10.1016/j.ccell.2022.05.009 · Cited by 686
Bressan, D., Battistoni, G., & Hannon, G. J. (2023) · Science · doi:10.1126/science.abq4964 · Cited by 622
The expanding vistas of spatial transcriptomics
Tian, L., Chen, F., & Macosko, E. Z. (2023) · Nature Biotechnology · doi:10.1038/s41587-022-01448-2 · Cited by 539
Self-citation
Metadata
- Authors
- Zhao, T., Chiang, Z. D., Morriss, J. W., LaFave, L. M., Murray, E. M., Del Priore, I., Meli, K., Lareau, C. A., Nadaf, N. M., Li, J., Earl, A. S., Macosko, E. Z., Jacks, T., Buenrostro, J. D., & Chen, F.
- Affiliations
- Broad Institute (US)
- Harvard University (US)
- Massachusetts Institute of Technology (US)
- Corresponding author
- Buenrostro, Jason D.
- Chen, Fei
- ORCID
- Venue
- Nature
- Published
- 2021-12-15
- Volume
- 601
- Issue
- 7891
- Pages
- 85-91
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- PMC
- PMC9301586
- OpenAlex
- W4200559225
- Cited by
- 268
- References
- 53
- Citations by year
- 2026: 51 · 2025: 51 · 2024: 75 · 2023: 53 · 2022: 37
- FWCI
- 13.34
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- Locations
- Nature (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- DSpace@MIT (Massachusetts Institute of Technology) (submittedVersion, cc-by-nc-sa)
- RePEc: Research Papers in Economics (submittedVersion)
- Funders
- Wellcome Trust
- National Institutes of Health (DP5OD024583)
- National Heart, Lung, and Blood Institute (DP2HL151353)
- National Human Genome Research Institute (R21HG009749, T32HG002295, R01HG010647)
- National Cancer Institute (UH3CA246632, R33CA246455)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Single-cell and spatial transcriptomics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer Genomics and Diagnostics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genomic variations and chromosomal abnormalities
- Keywords
- spatial genomics, tumor microenvironment, copy number alterations, tumor architecture, metastasis, spatial transcriptomics, tumor progression, gene expression regulation
- MeSH terms
- RNA-Seq, Animals, Clone Cells, Humans, Phenotype, Transcription, Genetic, Colorectal Neoplasms, Sequence Analysis, DNA, Genomics, Mice, DNA Copy Number Variations, Transcriptome
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
