Single-cell transcriptomics of human T cells reveals tissue and activation signatures in health and disease
Open accessAbstract
Human T cells coordinate adaptive immunity in diverse anatomic compartments through production of cytokines and effector molecules, but it is unclear how tissue site influences T cell persistence and function. Here, we use single cell RNA-sequencing (scRNA-seq) to define the heterogeneity of human T cells isolated from lungs, lymph nodes, bone marrow and blood, and their functional responses following stimulation. Through analysis of >50,000 resting and activated T cells, we reveal tissue T cell signatures in mucosal and lymphoid sites, and lineage-specific activation states across all sites including distinct effector states for CD8 + T cells and an interferon-response state for CD4 + T cells. Comparing scRNA-seq profiles of tumor-associated T cells to our dataset reveals predominant activated CD8 + compared to CD4 + T cell states within multiple tumor types. Our results therefore establish a high dimensional reference map of human T cell activation in health for analyzing T cells in disease.
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Transcriptomics provides insights into cellular diversity within tissues, making it a natural indicator of tissue diversity.
“Transcriptomics provides insights into cellular diversity within tissues, making it a natural indicator of tissue diversity25.”
From A visual–omics foundation model to bridge histopathology with spatial transcriptomics (2025) · cites this paper as [25]
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PD-1 and PD-L1 Immune Checkpoint Blockade to Treat Breast Cancer
Hartkopf, A. D., Taran, F., Wallwiener, M., Walter, C. B., Krämer, B., Grischke, E., & Brucker, S. Y. (2016) · Breast Care · doi:10.1159/000453569 · Cited by 30,989 · see citing works
Comprehensive Integration of Single-Cell Data
Stuart, T., Butler, A., Hoffman, P., Hafemeister, C., Papalexi, E., Mauck, W. M., Hao, Y., Stoeckius, M., Smibert, P., & Satija, R. (2019) · Cell · doi:10.1016/j.cell.2019.05.031 · Cited by 15,453 · see citing works
UMAP: Uniform Manifold Approximation and Projection
McInnes, L., Healy, J., Saul, N., & Großberger, L. (2018) · Journal of Open Source Software · doi:10.21105/joss.00861 · Cited by 9,826 · see citing works
UMAP: Uniform Manifold Approximation and Projection for Dimension Reduction
McInnes, L., Healy, J., & Melville, J. (2018) · arXiv · doi:10.48550/arxiv.1802.03426 · Cited by 7,101 · see citing works
Two subsets of memory T lymphocytes with distinct homing potentials and effector functions
Sallusto, F., Lenig, D., Förster, R., Lipp, M., & Lanzavecchia, A. (1999) · Nature · doi:10.1038/44385 · Cited by 5,846 · see citing works
Nivolumab in Previously Untreated Melanoma without <i>BRAF</i> Mutation
Robert, C., Long, G. V., Brady, B., Dutriaux, C., Maio, M., Mortier, L., Hassel, J. C., Rutkowski, P., McNeil, C., Kalinka-Warzocha, E., et al. (2015) · New England Journal of Medicine · doi:10.1056/nejmoa1412082 · Cited by 5,519 · see citing works
The future of immune checkpoint therapy
Sharma, P., & Allison, J. P. (2015) · Science · doi:10.1126/science.aaa8172 · Cited by 4,878 · see citing works
Wherry, E. J. (2011) · Nature Immunology · doi:10.1038/ni.2035 · Cited by 4,062 · see citing works
Restoring function in exhausted CD8 T cells during chronic viral infection
Barber, D. L., Wherry, E. J., Masopust, D., Zhu, B., Allison, J. P., Sharpe, A. H., Freeman, G. J., & Ahmed, R. (2005) · Nature · doi:10.1038/nature04444 · Cited by 3,960 · see citing works
Interferon-stimulated genes: A complex web of host defenses
Schneider, W. M., Chevillotte, M. D., & Rice, C. M. (2014) · Annual Review of Immunology · doi:10.1146/annurev-immunol-032713-120231 · Cited by 3,067 · see citing works
Deep generative modeling for single-cell transcriptomics
Lopez, R., Regier, J., Cole, M. B., Jordan, M. I., & Yosef, N. (2018) · Nature Methods · doi:10.1038/s41592-018-0229-2 · Cited by 2,530 · see citing works
Batch effects in single-cell RNA-sequencing data are corrected by matching mutual nearest neighbors
Haghverdi, L., Lun, A. T. L., Morgan, M. D., & Marioni, J. C. (2018) · Nature Biotechnology · doi:10.1038/nbt.4091 · Cited by 2,416 · see citing works
Data-Driven Phenotypic Dissection of AML Reveals Progenitor-like Cells that Correlate with Prognosis
Levine, J. H., Simonds, E. F., Bendall, S. C., Davis, K. L., Amir, E.-A. D., Tadmor, M. D., Litvin, O., Fienberg, H. G., Jager, A., Zunder, E. R., et al. (2015) · Cell · doi:10.1016/j.cell.2015.05.047 · Cited by 2,303 · 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
Molecular Signature of CD8+ T Cell Exhaustion during Chronic Viral Infection
Wherry, E. J., Ha, S.-J., Kaech, S. M., Haining, W. N., Sarkar, S., Kalia, V., Subramaniam, S., Blattman, J. N., Barber, D. L., & Ahmed, R. (2007) · Immunity · doi:10.1016/j.immuni.2007.09.006 · Cited by 2,103 · see citing works
Blackburn, S. D., Shin, H., Haining, W. N., Zou, T., Workman, C. J., Polley, A., Betts, M. R., Freeman, G. J., Vignali, D. A. A., & Wherry, E. J. (2009) · Nature Immunology · doi:10.1038/ni.1679 · Cited by 2,062 · see citing works
Defining T Cell States Associated with Response to Checkpoint Immunotherapy in Melanoma
Sade-Feldman, M., Yizhak, K., Bjorgaard, S. L., Ray, J. P., de Boer, C. G., Jenkins, R. W., Lieb, D. J., Chen, J. H., Frederick, D. T., Barzily-Rokni, M., et al. (2018) · Cell · doi:10.1016/j.cell.2018.10.038 · Cited by 2,053 · see citing works
Viral Immune Evasion Due to Persistence of Activated T Cells Without Effector Function
Zajac, A. J., Blattman, J. N., Murali-Krishna, K., Sourdive, D. J. D., Suresh, M., Altman, J. D., & Ahmed, R. (1998) · The Journal of Experimental Medicine · doi:10.1084/jem.188.12.2205 · Cited by 1,978 · see citing works
Single-Cell Map of Diverse Immune Phenotypes in the Breast Tumor Microenvironment
Azizi, E., Carr, A. J., Plitas, G., Cornish, A. E., Konopacki, C., Prabhakaran, S., Nainys, J., Wu, K., Kiseliovas, V., Setty, M., et al. (2018) · Cell · doi:10.1016/j.cell.2018.05.060 · Cited by 1,976 · see citing works
CD8 T Cell Exhaustion During Chronic Viral Infection and Cancer
McLane, L. M., Abdel-Hakeem, M. S., & Wherry, E. J. (2019) · Annual Review of Immunology · doi:10.1146/annurev-immunol-041015-055318 · Cited by 1,973 · see citing works
Single-cell RNA sequencing to explore immune cell heterogeneity
Papalexi, E., & Satija, R. (2018) · Nature Reviews Immunology · doi:10.1038/nri.2017.76 · Cited by 1,806 · see citing works
Phenotype molding of stromal cells in the lung tumor microenvironment
Lambrechts, D., Wauters, E., Boeckx, B., Aibar, S., Nittner, D., Burton, O., Bassez, A., Decaluwé, H., Pircher, A., Van den Eynde, K., et al. (2018) · Nature Medicine · doi:10.1038/s41591-018-0096-5 · Cited by 1,648 · see citing works
A step-by-step workflow for low-level analysis of single-cell RNA-seq data with Bioconductor
Lun, A. T. L., McCarthy, D. J., & Marioni, J. C. (2016) · F1000Research · doi:10.12688/f1000research.9501.2 · Cited by 1,586 · see citing works
Phan, G. Q., Yang, J. C., Sherry, R. M., Hwu, P., Topalian, S. L., Schwartzentruber, D. J., Restifo, N. P., Haworth, L. R., Seipp, C. A., Freezer, L. J., et al. (2003) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1533209100 · Cited by 1,575 · see citing works
A step-by-step workflow for low-level analysis of single-cell RNA-seq data
Lun, A. T. L., McCarthy, D. J., & Marioni, J. C. (2016) · F1000Research · doi:10.12688/f1000research.9501.1 · Cited by 1,511 · see citing works
Lineage tracking reveals dynamic relationships of T cells in colorectal cancer
Zhang, L., Yu, X., Zheng, L., Zhang, Y., Li, Y., Fang, Q., Gao, R., Kang, B., Zhang, Q., Huang, J. Y., et al. (2018) · Nature · doi:10.1038/s41586-018-0694-x · Cited by 1,505 · see citing works
Regev, A., Teichmann, S. A., Lander, E. S., Amit, I., Benoist, C. O., Birney, E., Bodenmiller, B., & al, E. (2017) · Zurich Open Repository and Archive (University of Zurich) · doi:10.5167/uzh-162597 · Cited by 1,457 · see citing works
Molecular Signature of CD8+ T Cell Exhaustion during Chronic Viral Infection
Wherry, E. J., Ha, S., Kaech, S. M., Haining, W. N., Sarkar, S., Kalia, V., Subramaniam, S., Blattman, J. N., Barber, D. L., & Ahmed, R. (2007) · Immunity · doi:10.1016/j.immuni.2007.11.006 · Cited by 1,355 · see citing works
The developmental pathway for CD103+CD8+ tissue-resident memory T cells of skin
Mackay, L. K., Rahimpour, A., Ma, J. Z., Collins, N., Stock, A. T., Hafon, M.-L., Vega-Ramos, J., Lauzurica, P., Mueller, S. N., Stefanovic, T., et al. (2013) · Nature Immunology · doi:10.1038/ni.2744 · Cited by 1,331 · see citing works
Interferon-stimulated genes and their antiviral effector functions
Schoggins, J. W., & Rice, C. M. (2011) · Current Opinion in Virology · doi:10.1016/j.coviro.2011.10.008 · Cited by 1,296 · see citing works
Human T cell development, localization, and function throughout life
Kumar, B. V., Connors, T. J., & Farber, D. L. (2018) · Immunity · doi:10.1016/j.immuni.2018.01.007 · Cited by 1,257 · see citing works
Comprehensive Classification of Retinal Bipolar Neurons by Single-Cell Transcriptomics
Shekhar, K., Lapan, S. W., Whitney, I. E., Tran, N. M., Macosko, E. Z., Kowalczyk, M., Adiconis, X., Levin, J. Z., Nemesh, J., Goldman, M., et al. (2016) · Cell · doi:10.1016/j.cell.2016.07.054 · Cited by 1,176 · see citing works
Pooling across cells to normalize single-cell RNA sequencing data with many zero counts
L. Lun, A. T., Bach, K., & Marioni, J. C. (2016) · Genome Biology · doi:10.1186/s13059-016-0947-7 · Cited by 1,108 · see citing works
CD8+ T Cells: Foot Soldiers of the Immune System
Zhang, N., & Bevan, M. J. (2011) · Immunity · doi:10.1016/j.immuni.2011.07.010 · Cited by 1,102 · see citing works
Li, H., van der Leun, A. M., Yofe, I., Lubling, Y., Gelbard-Solodkin, D., van Akkooi, A. C. J., van den Braber, M., Rozeman, E. A., Haanen, J. B. A. G., Blank, C. U., et al. (2019) · Cell · doi:10.1016/j.cell.2018.11.043 · Cited by 1,101 · see citing works
Molecular and functional profiling of memory CD8 T cell differentiation.
Kaech, S., Hemby, S., Kersh, E., & Ahmed, R. (2002) · Cell · doi:10.1016/s0092-8674(02)01139-x · Cited by 1,081 · see citing works
Single-cell sequencing reveals dissociation-induced gene expression in tissue subpopulations
van den Brink, S. C., Sage, F., Vértesy, Á., Spanjaard, B., Peterson-Maduro, J., Baron, C. S., Robin, C., & van Oudenaarden, A. (2017) · Nature Methods · doi:10.1038/nmeth.4437 · Cited by 1,072 · see citing works
Kumar, B. V., Ma, W., Miron, M., Granot, T., Guyer, R. S., Carpenter, D. J., Senda, T., Sun, X., Ho, S.-H., Lerner, H., et al. (2017) · Cell Reports · doi:10.1016/j.celrep.2017.08.078 · Cited by 1,068 · see citing works
Self-citationTissue-Resident Memory T Cells
Schenkel, J. M., & Masopust, D. (2014) · Immunity · doi:10.1016/j.immuni.2014.12.007 · Cited by 1,059 · see citing works
Differing Lymphokine Profiles of Functional Subsets of Human CD4 and CD8 T Cell Clones
Salgame, P. R., Abrams, J. S., Clayberger, C., Goldstein, H., Convit, J., Modlin, R. L., & Bloom, B. R. (1991) · Science · doi:10.1126/science.1681588 · Cited by 1,027 · see citing works
Control of Effector CD8 <sup>+</sup> T Cell Function by the Transcription Factor <i>Eomesodermin</i>
Pearce, E. L., Mullen, A. C., Martins, G. A., Krawczyk, C. M., Hutchins, A. S., Zediak, V. P., Banica, M., DiCioccio, C. B., Gross, D. A., Mao, C.-A., et al. (2003) · Science · doi:10.1126/science.1090148 · Cited by 1,014 · see citing works
Hobit and Blimp1 instruct a universal transcriptional program of tissue residency in lymphocytes
Mackay, L. K., Minnich, M., Kragten, N. A. M., Liao, Y., Nota, B., Seillet, C., Zaid, A., Man, K., Preston, S., Freestone, D., et al. (2016) · Science · doi:10.1126/science.aad2035 · Cited by 1,010 · see citing works
IL-7 is critical for homeostatic proliferation and survival of naïve T cells
Tan, J. T., Dudl, E. P., LeRoy, E., Murray, R. M., Sprent, J., Weinberg, K. I., & Surh, C. D. (2001) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.161126098 · Cited by 966 · see citing works
IL-21 and TGF-β are required for differentiation of human TH17 cells
Yang, L., Anderson, D. E., Baecher‐Allan, C., Hastings, W. D., Bettelli, E., Oukka, M., Kuchroo, V. K., & Hafler, D. A. (2008) · Nature · doi:10.1038/nature07021 · Cited by 926 · see citing works
Human memory T cells: generation, compartmentalization and homeostasis
Farber, D. L., Yudanin, N. A., & Restifo, N. P. (2014) · Nature Reviews Immunology · doi:10.1038/nri3567 · Cited by 897 · see citing works
Efficient integration of heterogeneous single-cell transcriptomes using Scanorama
Hie, B., Bryson, B. D., & Berger, B. (2019) · Nature Biotechnology · doi:10.1038/s41587-019-0113-3 · Cited by 853 · see citing works
Distribution and compartmentalization of human circulating and tissue-resident memory T cell subsets
Sathaliyawala, T., Kubota, M., Yudanin, N., Turner, D., Camp, P., Thome, J. J. C., Bickham, K. L., Lerner, H., Goldstein, M., Sykes, M., et al. (2013) · Immunity · doi:10.1016/j.immuni.2012.09.020 · Cited by 848 · see citing works
scmap: projection of single-cell RNA-seq data across data sets
(2018) · doi:10.1038/nmeth.4644 · Cited by 735 · see citing works
Resident memory CD8 T cells trigger protective innate and adaptive immune responses
Schenkel, J. M., Fraser, K. A., Beura, L. K., Pauken, K. E., Vezys, V., & Masopust, D. (2014) · Science · doi:10.1126/science.1254536 · Cited by 731 · see citing works
De Simone, M., Arrigoni, A., Rossetti, G., Gruarin, P., Ranzani, V., Politano, C., Bonnal, R. J. P., Provasi, E., Sarnicola, M. L., Panzeri, I., et al. (2016) · Immunity · doi:10.1016/j.immuni.2016.10.021 · Cited by 687 · see citing works
CD49a Expression Defines Tissue-Resident CD8 + T Cells Poised for Cytotoxic Function in Human Skin
Cheuk, S., Schlums, H., Gallais Sérézal, I., Martini, E., Chiang, S. C., Marquardt, N., Gibbs, A., Detlofsson, E., Introini, A., Forkel, M., et al. (2017) · Immunity · doi:10.1016/j.immuni.2017.01.009 · Cited by 678 · see citing works
Teijaro, J. R., Turner, D., Pham, Q., Wherry, E. J., Lefrançois, L., & Farber, D. L. (2011) · The Journal of Immunology · doi:10.4049/jimmunol.1102243 · Cited by 641 · see citing works
Self-citationKaech, S. M., & Wherry, E. J. (2007) · Immunity · doi:10.1016/j.immuni.2007.08.007 · Cited by 619 · see citing works
Spatial map of human T cell compartmentalization and maintenance over decades of life
Thome, J. J. C., Yudanin, N., Ohmura, Y., Kubota, M., Grinshpun, B., Sathaliyawala, T., Kato, T., Lerner, H., Shen, Y., & Farber, D. L. (2014) · Cell · doi:10.1016/j.cell.2014.10.026 · Cited by 587 · see citing works
Self-citationSingle-cell transcriptomics to explore the immune system in health and disease
Stubbington, M. J. T., Rozenblatt–Rosen, O., Regev, A., & Teichmann, S. A. (2017) · Science · doi:10.1126/science.aan6828 · Cited by 560 · see citing works
Interleukin 7 Regulates the Survival and Generation of Memory CD4 Cells
Kondrack, R. M., Harbertson, J., Tan, J. T., McBreen, M. E., Surh, C. D., & Bradley, L. M. (2003) · The Journal of Experimental Medicine · doi:10.1084/jem.20030735 · Cited by 470 · see citing works
Banga, R., Procopio, F. A., Noto, A., Pollakis, G., Cavassini, M. L., Ohmiti, K., Corpataux, J.-M., de Leval, L., Pantaleo, G., & Perreau, M. (2016) · Nature Medicine · doi:10.1038/nm.4113 · Cited by 466 · see citing works
Programs for the persistence, vigilance and control of human CD8+ lung-resident memory T cells
Hombrink, P., Helbig, C., Backer, R. A., Piet, B., Oja, A. E., Stark, R., Brasser, G., Jongejan, A., Jonkers, R. E., Nota, B., et al. (2016) · Nature Immunology · doi:10.1038/ni.3589 · Cited by 455 · see citing works
CD4+ T Cells Expressing PD-1, TIGIT and LAG-3 Contribute to HIV Persistence during ART
Fromentin, R., Bakeman, W., Lawani, M. B., Khoury, G., Hartogensis, W., DaFonseca, S., Killian, M. L., Epling, L., Hoh, R., Sinclair, E., et al. (2016) · PLoS Pathogens · doi:10.1371/journal.ppat.1005761 · Cited by 418 · see citing works
Single-cell gene expression reveals a landscape of regulatory T cell phenotypes shaped by the TCR
Zemmour, D., Zilionis, R., Kiner, E., Klein, A. M., Mathis, D., & Benoist, C. (2018) · Nature Immunology · doi:10.1038/s41590-018-0051-0 · Cited by 384 · see citing works
Yuan, J. D., Gnjatic, S., Li, H., Powel, S., Gallardo, H. F., Ritter, E., Ku, G. Y., Jungbluth, A. A., Segal, N. H., Rasalan, T. S., et al. (2008) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0810114105 · Cited by 346 · see citing works
Self-citationDetection and removal of barcode swapping in single-cell RNA-seq data
Griffiths, J. A., Richard, A. C., Bach, K., Lun, A. T. L., & Marioni, J. C. (2018) · Nature Communications · doi:10.1038/s41467-018-05083-x · Cited by 324 · see citing works
Helper T cell diversity and plasticity
Nakayamada, S., Takahashi, H., Kanno, Y., & O’Shea, J. J. (2012) · Current Opinion in Immunology · doi:10.1016/j.coi.2012.01.014 · Cited by 317 · see citing works
Park, S. L., Zaid, A., Hor, J. L., Christo, S. N., Prier, J. E., Davies, B., Alexandre, Y. O., Gregory, J. L., Russell, T., Gebhardt, T., et al. (2018) · Nature Immunology · doi:10.1038/s41590-017-0027-5 · Cited by 317 · see citing works
Thome, J. J. C., Bickham, K. L., Ohmura, Y., Kubota, M., Matsuoka, N., Gordon, C., Granot, T., Griesemer, A., Lerner, H., Kato, T., et al. (2016) · Nature Medicine · doi:10.1038/nm.4008 · Cited by 305 · see citing works
Differing lymphokine profiles of functional subsets of human CD4 and CD8 T cell clones
Salgame, P., Js, A., Clayberger, C., et al. (1991) · Science · doi:10.1126/science.254.5029.279 · Cited by 302 · see citing works
Joint analysis of heterogeneous single-cell RNA-seq dataset collections
Barkas, N., Petukhov, V., Nikolaeva, D., Lozinsky, Y., Demharter, S., Khodosevich, K., & Kharchenko, P. V. (2019) · Nature Methods · doi:10.1038/s41592-019-0466-z · Cited by 292 · see citing works
Dendritic Cells Display Subset and Tissue-Specific Maturation Dynamics over Human Life
Granot, T., Senda, T., Carpenter, D. J., Matsuoka, N., Weiner, J. I., Gordon, C. L., Miron, M., Kumar, B. V., Griesemer, A. D., Ho, S., et al. (2017) · Immunity · doi:10.1016/j.immuni.2017.02.019 · Cited by 284 · see citing works
Self-citationHuman bone marrow assessment by single-cell RNA sequencing, mass cytometry, and flow cytometry
Oetjen, K. A., Lindblad, K. E., Goswami, M., Gui, G., Dagur, P. K., Lai, C., Dillon, L. W., McCoy, J. P., & Hourigan, C. S. (2018) · JCI Insight · doi:10.1172/jci.insight.124928 · Cited by 272 · see citing works
Dominguez, C. X., Amezquita, R., Guan, T.-X., Marshall, H. D., Joshi, N., Kleinstein, S., & Kaech, S. (2015) · Journal of Experimental Medicine · doi:10.1084/jem.20150186 · Cited by 265 · see citing works
Using single-cell genomics to understand developmental processes and cell fate decisions
Griffiths, J. A., Scialdone, A., & Marioni, J. C. (2018) · Molecular Systems Biology · doi:10.15252/msb.20178046 · Cited by 250 · see citing works
Single-cell transcriptome analysis of lineage diversity in high-grade glioma
Yuan, J., Levitin, H. M., Frattini, V., Bush, E. C., Boyett, D. M., Samanamud, J. L., Ceccarelli, M., Dovas, A., Zanazzi, G. J., Canoll, P., et al. (2018) · Genome Medicine · doi:10.1186/s13073-018-0567-9 · Cited by 237 · see citing works
Self-citationSingle-Cell Transcriptomic Analysis of Tumor Heterogeneity
Levitin, H. M., Yuan, J., & Sims, P. A. (2018) · Trends in cancer · doi:10.1016/j.trecan.2018.02.003 · Cited by 194 · see citing works
Self-citationLong-term maintenance of human naive T cells through in situ homeostasis in lymphoid tissue sites
Thome, J. J. C., Grinshpun, B., Kumar, B. V., Kubota, M., Ohmura, Y., Lerner, H., Sempowski, G. D., Shen, Y., & Farber, D. L. (2016) · Science Immunology · doi:10.1126/sciimmunol.aah6506 · Cited by 162 · see citing works
Wilk, M. M., Misiak, A., McManus, R. M., Allen, A. C., Lynch, M. A., & Mills, K. H. G. (2017) · The Journal of Immunology · doi:10.4049/jimmunol.1602051 · Cited by 161 · see citing works
Zanini, F., Robinson, M., Croote, D., Sahoo, M. K., Sanz, A. M., Ortiz-Lasso, E., Albornóz, L. L., Rosso, F., Montoya, J. G., Goo, L., et al. (2018) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1813819115 · Cited by 157 · see citing works
Swanson, B. J., Murakami, M., Mitchell, T. C., Kappler, J. W., & Marrack, P. (2002) · Immunity · doi:10.1016/s1074-7613(02)00456-9 · Cited by 137 · see citing works
Levitin, H. M., Yuan, J., Cheng, Y. L., Ruiz, F. J. R., Bush, E. C., Bruce, J. N., Canoll, P., Iavarone, A., Lasorella, A., Blei, D. M., et al. (2019) · Molecular Systems Biology · doi:10.15252/msb.20188557 · Cited by 107 · see citing works
Self-citationAquaporin expression in human lymphocytes and dendritic cells
Moon, C., Rousseau, R. F., Soria, J., Hoque, M. O., Lee, J., Jang, S. J., Trink, B., Sidransky, D., & Mao, L. (2004) · American Journal of Hematology · doi:10.1002/ajh.10476 · Cited by 84 · see citing works
Miron, M., Kumar, B. V., Meng, W., Granot, T., Carpenter, D. J., Senda, T., Chen, D., Rosenfeld, A. M., Zhang, B., Lerner, H., et al. (2018) · The Journal of Immunology · doi:10.4049/jimmunol.1800716 · Cited by 78 · see citing works
Self-citationCarpenter, D. J., Granot, T., Matsuoka, N., Senda, T., Kumar, B. V., Thome, J. J. C., Gordon, C. L., Miron, M., Weiner, J. I., Connors, T. J., et al. (2017) · American Journal of Transplantation · doi:10.1111/ajt.14434 · Cited by 77 · see citing works
Self-citationMulti-Omics Profiling of the Tumor Microenvironment: Paving the Way to Precision Immuno-Oncology
Finotello, F., & Eduati, F. (2018) · Frontiers in Oncology · doi:10.3389/fonc.2018.00430 · Cited by 75 · see citing works
Do most lymphocytes in humans really reside in the gut?
Ganusov, V., & de Boer, R. D. (2007) · Trends in immunology · doi:10.1016/j.it.2007.08.009 · Cited by 60 · see citing works
Functional heterogeneity of human tissue-resident memory T cells based on dye efflux capacities
Kumar, B. V., Kratchmarov, R., Miron, M., Carpenter, D. J., Senda, T., Lerner, H., Friedman, A. L., Reiner, S. L., & Färber, D. L. (2018) · JCI Insight · doi:10.1172/jci.insight.123568 · Cited by 49 · see citing works
Self-citationLearning about the functions of NME/NM23: lessons from knockout mice to silencing strategies
Boissan, M., & Lacombe, M. (2011) · Naunyn-Schmiedeberg s Archives of Pharmacology · doi:10.1007/s00210-011-0649-3 · Cited by 45 · see citing works
HOPX: The Unusual Homeodomain-Containing Protein
Mariotto, A., Pavlova, O., Park, H., et al. (2016) · Journal of Investigative Dermatology · doi:10.1016/j.jid.2016.01.032 · Cited by 45 · see citing works
Chen, R., Peng, P., Wen, B., et al. (2016) · Translational Oncology · doi:10.1016/j.tranon.2015.11.010 · Cited by 21 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
The evolving tumor microenvironment: From cancer initiation to metastatic outgrowth
de Visser, K. E., & Joyce, J. A. (2023) · Cancer Cell · doi:10.1016/j.ccell.2023.02.016 · Cited by 4,059 · see citing works
A human brain vascular atlas reveals diverse mediators of Alzheimer’s risk
Yang, A. C., Vest, R. T., Kern, F., Lee, D. P., Agam, M., Maat, C. A., Losada, P. M., Chen, M. B., Schaum, N., Khoury, N., et al. (2022) · Nature · doi:10.1038/s41586-021-04369-3 · Cited by 797 · see citing works
The Specious Art of Single-Cell Genomics
Chari, T., & Pachter, L. (2021) · doi:10.1101/2021.08.25.457696 · Cited by 379 · see citing works
Applying high-dimensional single-cell technologies to the analysis of cancer immunotherapy
Gohil, S. H., Iorgulescu, J. B., Braun, D. A., Keskin, D. B., & Livak, K. J. (2021) · Nature Reviews Clinical Oncology · doi:10.1038/s41571-020-00449-x · Cited by 282 · see citing works
Marron, T. U., Fiel, M. I., Hamon, P., Fiaschi, N., Kim, E., Ward, S. C., Zhao, Z., Kim, J., Kennedy, P., Gunasekaran, G., et al. (2022) · The Lancet Gastroenterology & Hepatology · doi:10.1016/s2468-1253(21)00385-x · Cited by 239 · see citing works
Delacher, M., Simon, M., Sanderink, L., Hotz-Wagenblatt, A., Wuttke, M., Schambeck, K., Schmidleithner, L., Bittner, S., Pant, A., Ritter, U., et al. (2021) · Immunity · doi:10.1016/j.immuni.2021.03.007 · Cited by 164 · see citing works
Ketolysis drives CD8+ T cell effector function through effects on histone acetylation
Luda, K. M., Longo, J., Kitchen-Goosen, S. M., Duimstra, L. R., Ma, E. H., Watson, M. J., Oswald, B. M., Fu, Z., Madaj, Z., Kupai, A., et al. (2023) · Immunity · doi:10.1016/j.immuni.2023.07.002 · Cited by 140 · see citing works
TREM2 macrophages induced by human lipids drive inflammation in acne lesions
Do, T. H., Ma, F., Andrade, P. R., Teles, R., de Andrade Silva, B. J., Hu, C., Espinoza, A., Hsu, J.-E., Cho, C.-S., Kim, M., et al. (2022) · Science Immunology · doi:10.1126/sciimmunol.abo2787 · Cited by 139 · see citing works
Ashary, N., Bhide, A., Chakraborty, P., Colaco, S., Mishra, A., Chhabria, K., Jolly, M. K., & Modi, D. (2020) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2020.00783 · Cited by 121 · see citing works
A visual–omics foundation model to bridge histopathology with spatial transcriptomics
Chen, W., Zhang, P., Tran, T. N., Xiao, Y., Li, S., Shah, V. V., Cheng, H., Brannan, K. W., Youker, K., Lai, L., et al. (2025) · Nature Methods · doi:10.1038/s41592-025-02707-1 · Cited by 118 · see citing works
“Transcriptomics provides insights into cellular diversity within tissues, making it a natural indicator of tissue diversity 25 .”
GD2 or HER2 targeting T cell engaging bispecific antibodies to treat osteosarcoma
Park, J. A., & Cheung, N.-K. V. (2020) · Journal of Hematology & Oncology · doi:10.1186/s13045-020-01012-y · Cited by 88 · see citing works
Qiu, M.-Z., Wang, C., Wu, Z., Zhao, Q., Zhao, Z., Huang, C.-Y., Wu, W., Yang, L.-Q., Zhou, Z.-W., Zheng, Y., et al. (2023) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-023-01622-1 · Cited by 58 · see citing works
The Multifaceted Role of Regulatory T Cells in Breast Cancer
Kos, K., & de Visser, K. E. (2021) · Annual Review of Cancer Biology · doi:10.1146/annurev-cancerbio-042920-104912 · Cited by 58 · see citing works
A human brain vascular atlas reveals diverse cell mediators of Alzheimer’s disease risk
Yang, A. C., Vest, R. T., Kern, F., Lee, D. P., Maat, C. A., Losada, P. M., Chen, M. B., Agam, M., Schaum, N., Khoury, N., et al. (2021) · doi:10.1101/2021.04.26.441262 · Cited by 48 · see citing works
van Gisbergen, K. P. J. M., Zens, K. D., & Münz, C. (2021) · European Journal of Immunology · doi:10.1002/eji.202049062 · Cited by 39 · see citing works
Sfaira accelerates data and model reuse in single cell genomics
Fischer, D. S., Dony, L., König, M., Moeed, A., Zappia, L., Heumos, L., Tritschler, S., Holmberg, O., Aliee, H., & Theis, F. J. (2021) · Genome Biology · doi:10.1186/s13059-021-02452-6 · Cited by 33 · see citing works
Zareie, P., Weiss, E. S., Kaplan, D. H., & Mackay, L. K. (2025) · Nature Immunology · doi:10.1038/s41590-025-02145-3 · Cited by 29 · see citing works
Mikkilineni, L., Natrakul, D. A., Lam, N., Manasanch, E. E., Mann, J., Weissler, K. A., Wong, N., Brudno, J. N., Goff, S. L., Yang, J. C., et al. (2024) · Molecular Therapy · doi:10.1016/j.ymthe.2023.12.018 · Cited by 16 · see citing works
Gallego-Cortés, A., Sánchez-Gaona, N., Mancebo-Pérez, C., Ruiz-Isant, O., Benítez-Martínez, A., Landolfi, S., Castellví, J., Pumarola, F., Ortiz, N., Llano, I., et al. (2025) · Nature Communications · doi:10.1038/s41467-025-65288-9 · Cited by 12 · see citing works
- Authors
- Szabo, P. A., Levitin, H. M., Miron, M., Snyder, M. E., Senda, T., Yuan, J., Cheng, Y. L., Bush, E. C., Dogra, P., Thapa, P., Farber, D. L., & Sims, P. A.
- Affiliations
- Columbia University Irving Medical Center (US)
- Corresponding author
- Sims, Peter A.
- ORCID
- Venue
- Nature Communications
- Published
- 2019-10-17
- Volume
- 10
- Issue
- 1
- Pages
- 4706-4706
- ISSN
- 2041-1723 (ISSN-L)
- PMC
- PMC6797728
- OpenAlex
- W2980897730
- Cited by
- 756
- References
- 87
- Citations by year
- 2026: 106 · 2025: 139 · 2024: 117 · 2023: 107 · 2022: 127 · 2021: 114 · 2020: 43 · 2019: 2 · 2013: 1
- FWCI
- 23.75
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Nature Communications (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
- Funders
- U.S. Department of Health & Human Services | NIH | National Institute of Allergy and Infectious Diseases (AI128949)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Single-cell and spatial transcriptomics
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Health Sciences › Medicine › Oncology › Cancer Immunotherapy and Biomarkers
- Keywords
- human T cells, T cell heterogeneity, T cell activation, CD8+ T cells, CD4+ T cells, interferon response, mucosal immunity, lymphoid tissue, tumor-infiltrating T cells, adaptive immunity
- MeSH terms
- Cells, Cultured, Humans, Lung, Lymph Nodes, Lymphocyte Activation, Mucous Membrane, Neoplasms, T-Lymphocytes, CD4-Positive T-Lymphocytes, CD8-Positive T-Lymphocytes, Single-Cell Analysis, 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.
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