Cited by 1,059Single-cell and spatial transcriptomicsBiotin and Related StudiesGenomics and Chromatin Dynamics

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Integrating single-cell and spatial transcriptomics to elucidate intercellular tissue dynamics

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Longo, Sophia K., Guo, Margaret G., Ji, Andrew L., Khavari, Paul A.·2021·Nature Reviews Genetics

DOI 10.1038/s41576-021-00370-8PMC PMC9888017

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Abstract

Single-cell RNA sequencing (scRNA-seq) identifies cell subpopulations within tissue but does not capture their spatial distribution nor reveal local networks of intercellular communication acting in situ. A suite of recently developed techniques that localize RNA within tissue, including multiplexed in situ hybridization and in situ sequencing (here defined as high-plex RNA imaging) and spatial barcoding, can help address this issue. However, no method currently provides as complete a scope of the transcriptome as does scRNA-seq, underscoring the need for approaches to integrate single-cell and spatial data. Here, we review efforts to integrate scRNA-seq with spatial transcriptomics, including emerging integrative computational methods, and propose ways to effectively combine current methodologies.

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Additional file 16 of Integrated transcriptomics uncovers an enhanced association between the prion protein gene expression and vesicle dynamics signatures in glioblastomas
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Additional file 7 of Integrated single-nucleus sequencing and spatial architecture analysis identified distinct injured-proximal tubular types in calculi rats
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Additional file 11 of Integrating single-nucleus RNA sequencing and spatial transcriptomics to elucidate a specialized subpopulation of astrocytes, microglia and vascular cells in brains of mouse model of lipopolysaccharide-induced sepsis-associated encephalopathy
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Additional file 4 of Integrated single-nucleus sequencing and spatial architecture analysis identified distinct injured-proximal tubular types in calculi rats
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Additional file 3 of Benchmarking clustering, alignment, and integration methods for spatial transcriptomics
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Additional file 1 of Sex-biased gene expression and gene-regulatory networks of sex-biased adverse event drug targets and drug metabolism genes
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Additional file 1 of Integrated single-nucleus sequencing and spatial architecture analysis identified distinct injured-proximal tubular types in calculi rats
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Additional file 9 of Integrating single-nucleus RNA sequencing and spatial transcriptomics to elucidate a specialized subpopulation of astrocytes, microglia and vascular cells in brains of mouse model of lipopolysaccharide-induced sepsis-associated encephalopathy
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Additional file 10 of Integrated transcriptomics uncovers an enhanced association between the prion protein gene expression and vesicle dynamics signatures in glioblastomas
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Additional file 6 of Integrated single-nucleus sequencing and spatial architecture analysis identified distinct injured-proximal tubular types in calculi rats
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Additional file 2 of Benchmarking clustering, alignment, and integration methods for spatial transcriptomics
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Additional file 6 of Integrated transcriptomics uncovers an enhanced association between the prion protein gene expression and vesicle dynamics signatures in glioblastomas
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Additional file 7 of Integrated transcriptomics uncovers an enhanced association between the prion protein gene expression and vesicle dynamics signatures in glioblastomas
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Additional file 4 of Integrated transcriptomics uncovers an enhanced association between the prion protein gene expression and vesicle dynamics signatures in glioblastomas
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Additional file 1 of Integrated transcriptomics uncovers an enhanced association between the prion protein gene expression and vesicle dynamics signatures in glioblastomas
Boccacino, J. M., dos Santos Peixoto, R., Fernandes, C. F. D. L., Cangiano, G., Sola, P. R., Coelho, B. P., Prado, M. B., Melo-Escobar, M. I., de Sousa, B. P., Ayyadhury, S., et al. (2024) · Figshare · doi:10.6084/m9.figshare.25210540
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Additional file 6 of Integrating single-nucleus RNA sequencing and spatial transcriptomics to elucidate a specialized subpopulation of astrocytes, microglia and vascular cells in brains of mouse model of lipopolysaccharide-induced sepsis-associated encephalopathy
Zhu, Y., Zhang, Y., He, S., Yi, S., Feng, H., Xia, X., Fang, X., Gong, X., & Zhao, P. (2024) · Figshare · doi:10.6084/m9.figshare.26743061
Additional file 12 of Integrating single-nucleus RNA sequencing and spatial transcriptomics to elucidate a specialized subpopulation of astrocytes, microglia and vascular cells in brains of mouse model of lipopolysaccharide-induced sepsis-associated encephalopathy
Zhu, Y., Zhang, Y., He, S., Yi, S., Feng, H., Xia, X., Fang, X., Gong, X., & Zhao, P. (2024) · Figshare · doi:10.6084/m9.figshare.26743079
Additional file 14 of Integrated transcriptomics uncovers an enhanced association between the prion protein gene expression and vesicle dynamics signatures in glioblastomas
Boccacino, J. M., dos Santos Peixoto, R., Fernandes, C. F. D. L., Cangiano, G., Sola, P. R., Coelho, B. P., Prado, M. B., Melo-Escobar, M. I., de Sousa, B. P., Ayyadhury, S., et al. (2024) · Figshare · doi:10.6084/m9.figshare.26680235
Additional file 17 of Integrated transcriptomics uncovers an enhanced association between the prion protein gene expression and vesicle dynamics signatures in glioblastomas
Boccacino, J. M., dos Santos Peixoto, R., Fernandes, C. F. D. L., Cangiano, G., Sola, P. R., Coelho, B. P., Prado, M. B., Melo-Escobar, M. I., de Sousa, B. P., Ayyadhury, S., et al. (2024) · Figshare · doi:10.6084/m9.figshare.26680244
Additional file 13 of Integrated transcriptomics uncovers an enhanced association between the prion protein gene expression and vesicle dynamics signatures in glioblastomas
Boccacino, J. M., dos Santos Peixoto, R., Fernandes, C. F. D. L., Cangiano, G., Sola, P. R., Coelho, B. P., Prado, M. B., Melo-Escobar, M. I., de Sousa, B. P., Ayyadhury, S., et al. (2024) · Figshare · doi:10.6084/m9.figshare.26680232
Additional file 18 of Integrated transcriptomics uncovers an enhanced association between the prion protein gene expression and vesicle dynamics signatures in glioblastomas
Boccacino, J. M., dos Santos Peixoto, R., Fernandes, C. F. D. L., Cangiano, G., Sola, P. R., Coelho, B. P., Prado, M. B., Melo-Escobar, M. I., de Sousa, B. P., Ayyadhury, S., et al. (2024) · Figshare · doi:10.6084/m9.figshare.26680247
Additional file 2 of scHolography: a computational method for single-cell spatial neighborhood reconstruction and analysis
Fu, Y. C., Das, A., Wang, D., Braun, R., & Yi, R. (2024) · Figshare · doi:10.6084/m9.figshare.26094505
Additional file 7 of Integrating single-nucleus RNA sequencing and spatial transcriptomics to elucidate a specialized subpopulation of astrocytes, microglia and vascular cells in brains of mouse model of lipopolysaccharide-induced sepsis-associated encephalopathy
Zhu, Y., Zhang, Y., He, S., Yi, S., Feng, H., Xia, X., Fang, X., Gong, X., & Zhao, P. (2024) · Figshare · doi:10.6084/m9.figshare.26743064
Additional file 2 of Multi-slice spatial transcriptome domain analysis with SpaDo
Duan, B., Chen, S., Cheng, X., & Liu, Q. (2024) · Figshare · doi:10.6084/m9.figshare.25441029
Additional file 1 of Multi-slice spatial transcriptome domain analysis with SpaDo
Duan, B., Chen, S., Cheng, X., & Liu, Q. (2024) · Figshare · doi:10.6084/m9.figshare.25440922
Additional file 6 of Sex-biased gene expression and gene-regulatory networks of sex-biased adverse event drug targets and drug metabolism genes
Fisher, J. L., Clark, A. D., Jones, E. F., & Lasseigne, B. N. (2024) · Figshare · doi:10.6084/m9.figshare.26658760
Additional file 5 of Sex-biased gene expression and gene-regulatory networks of sex-biased adverse event drug targets and drug metabolism genes
Fisher, J. L., Clark, A. D., Jones, E. F., & Lasseigne, B. N. (2024) · Figshare · doi:10.6084/m9.figshare.26658757
Additional file 12 of Integrated transcriptomics uncovers an enhanced association between the prion protein gene expression and vesicle dynamics signatures in glioblastomas
Boccacino, J. M., dos Santos Peixoto, R., Fernandes, C. F. D. L., Cangiano, G., Sola, P. R., Coelho, B. P., Prado, M. B., Melo-Escobar, M. I., de Sousa, B. P., Ayyadhury, S., et al. (2024) · Figshare · doi:10.6084/m9.figshare.26680229
Additional file 3 of Integrated transcriptomics uncovers an enhanced association between the prion protein gene expression and vesicle dynamics signatures in glioblastomas
Boccacino, J. M., dos Santos Peixoto, R., Fernandes, C. F. D. L., Cangiano, G., Sola, P. R., Coelho, B. P., Prado, M. B., Melo-Escobar, M. I., de Sousa, B. P., Ayyadhury, S., et al. (2024) · Figshare · doi:10.6084/m9.figshare.26680202
Additional file 4 of Sex-biased gene expression and gene-regulatory networks of sex-biased adverse event drug targets and drug metabolism genes
Fisher, J. L., Clark, A. D., Jones, E. F., & Lasseigne, B. N. (2024) · Figshare · doi:10.6084/m9.figshare.26658751
Additional file 8 of Integrated single-nucleus sequencing and spatial architecture analysis identified distinct injured-proximal tubular types in calculi rats
Wang, Z., Deng, Q., Gu, Y., Li, M., Chen, Y. K., Wang, J., Zhang, Y., Zhang, J., Hu, Q., Shenping, Z., et al. (2023) · Figshare · doi:10.6084/m9.figshare.22978181
Additional file 17 of Sex-biased gene expression and gene-regulatory networks of sex-biased adverse event drug targets and drug metabolism genes
Fisher, J. L., Clark, A. D., Jones, E. F., & Lasseigne, B. N. (2024) · Figshare · doi:10.6084/m9.figshare.26658796
Additional file 8 of Integrating single-nucleus RNA sequencing and spatial transcriptomics to elucidate a specialized subpopulation of astrocytes, microglia and vascular cells in brains of mouse model of lipopolysaccharide-induced sepsis-associated encephalopathy
Zhu, Y., Zhang, Y., He, S., Yi, S., Feng, H., Xia, X., Fang, X., Gong, X., & Zhao, P. (2024) · Figshare · doi:10.6084/m9.figshare.26743067
Additional file 16 of Sex-biased gene expression and gene-regulatory networks of sex-biased adverse event drug targets and drug metabolism genes
Fisher, J. L., Clark, A. D., Jones, E. F., & Lasseigne, B. N. (2024) · Figshare · doi:10.6084/m9.figshare.26658793
Additional file 3 of Sex-biased gene expression and gene-regulatory networks of sex-biased adverse event drug targets and drug metabolism genes
Fisher, J. L., Clark, A. D., Jones, E. F., & Lasseigne, B. N. (2024) · Figshare · doi:10.6084/m9.figshare.26658748
Additional file 15 of Integrated transcriptomics uncovers an enhanced association between the prion protein gene expression and vesicle dynamics signatures in glioblastomas
Boccacino, J. M., dos Santos Peixoto, R., Fernandes, C. F. D. L., Cangiano, G., Sola, P. R., Coelho, B. P., Prado, M. B., Melo-Escobar, M. I., de Sousa, B. P., Ayyadhury, S., et al. (2024) · Figshare · doi:10.6084/m9.figshare.26680238
Additional file 7 of Sex-biased gene expression and gene-regulatory networks of sex-biased adverse event drug targets and drug metabolism genes
Fisher, J. L., Clark, A. D., Jones, E. F., & Lasseigne, B. N. (2024) · Figshare · doi:10.6084/m9.figshare.26658763
Additional file 19 of Sex-biased gene expression and gene-regulatory networks of sex-biased adverse event drug targets and drug metabolism genes
Fisher, J. L., Clark, A. D., Jones, E. F., & Lasseigne, B. N. (2024) · Figshare · doi:10.6084/m9.figshare.26658802
Additional file 2 of Integrated single-nucleus sequencing and spatial architecture analysis identified distinct injured-proximal tubular types in calculi rats
Wang, Z., Deng, Q., Gu, Y., Li, M., Chen, Y. K., Wang, J., Zhang, Y., Zhang, J., Hu, Q., Shenping, Z., et al. (2023) · Figshare · doi:10.6084/m9.figshare.22978160
Additional file 12 of Sex-biased gene expression and gene-regulatory networks of sex-biased adverse event drug targets and drug metabolism genes
Fisher, J. L., Clark, A. D., Jones, E. F., & Lasseigne, B. N. (2024) · Figshare · doi:10.6084/m9.figshare.26658778
Additional file 5 of Integrating single-nucleus RNA sequencing and spatial transcriptomics to elucidate a specialized subpopulation of astrocytes, microglia and vascular cells in brains of mouse model of lipopolysaccharide-induced sepsis-associated encephalopathy
Zhu, Y., Zhang, Y., He, S., Yi, S., Feng, H., Xia, X., Fang, X., Gong, X., & Zhao, P. (2024) · Figshare · doi:10.6084/m9.figshare.26743058
Additional file 13 of Sex-biased gene expression and gene-regulatory networks of sex-biased adverse event drug targets and drug metabolism genes
Fisher, J. L., Clark, A. D., Jones, E. F., & Lasseigne, B. N. (2024) · Figshare · doi:10.6084/m9.figshare.26658781
Additional file 11 of Integrated transcriptomics uncovers an enhanced association between the prion protein gene expression and vesicle dynamics signatures in glioblastomas
Boccacino, J. M., dos Santos Peixoto, R., Fernandes, C. F. D. L., Cangiano, G., Sola, P. R., Coelho, B. P., Prado, M. B., Melo-Escobar, M. I., de Sousa, B. P., Ayyadhury, S., et al. (2024) · Figshare · doi:10.6084/m9.figshare.26680226
Additional file 3 of Single-cell analysis of human prepuce reveals dynamic changes in gene regulation and cellular communications
Tan, F., Xuan, Y., Long, L., Yu, Y., Zhang, C., Liang, P., Wang, Y., Chen, M., Wen, J., & Chen, G. (2023) · Figshare · doi:10.6084/m9.figshare.24077048
Additional file 8 of Integrated transcriptomics uncovers an enhanced association between the prion protein gene expression and vesicle dynamics signatures in glioblastomas
Boccacino, J. M., dos Santos Peixoto, R., Fernandes, C. F. D. L., Cangiano, G., Sola, P. R., Coelho, B. P., Prado, M. B., Melo-Escobar, M. I., de Sousa, B. P., Ayyadhury, S., et al. (2024) · Figshare · doi:10.6084/m9.figshare.26680217

Authors: Longo, S. K., Guo, M. G., Ji, A. L., & Khavari, P. A.
Affiliations: Stanford Cancer Institute (US)
VA Palo Alto Health Care System (US)
Corresponding author: Khavari, Paul A.
ORCID: Longo, Sophia K.
Guo, Margaret G.
Ji, Andrew L.
Khavari, Paul A.
Venue: Nature Reviews Genetics
Publisher: Springer Science and Business Media LLC
Published: 2021-06-18
Volume: 22
Issue: 10
Pages: 627-644
ISSN: 1471-0056 (ISSN-L)
1471-0064
DOI: 10.1038/s41576-021-00370-8
PMC: PMC9888017
OpenAlex: W3171692328
Cited by: 1,059
References: 183
Citations by year: 2026: 233 · 2025: 203 · 2024: 242 · 2023: 196 · 2022: 157 · 2021: 27
FWCI: 16.92
Type: journal article
Language: en
Open access: green
www.ncbi.nlm.nih.gov
Licence: www.springernature.com/gp/researchers/text-and-data-mining (tdm)
www.springernature.com/gp/researchers/text-and-data-mining (vor)
Locations: Nature Reviews Genetics (publishedVersion)
PubMed (publishedVersion)
PubMed Central (acceptedVersion)
Funders: National Cancer Institute (R01CA142635)
National Institute of Arthritis and Musculoskeletal and Skin Diseases (R01AR049737, R01AR043799, R01AR076965)
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Single-cell and spatial transcriptomics
Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Biotin and Related Studies
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
Keywords: single-cell RNA sequencing, spatial transcriptomics, data integration, intercellular communication, tissue dynamics, in situ sequencing, cell localization
MeSH terms: Animals, Cell Communication, Humans, Software, Sequence Analysis, RNA, Computational Biology, Single-Cell Analysis, Transcriptome

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Integrating single-cell and spatial transcriptomics to elucidate intercellular tissue dynamics

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