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Spatial transcriptomics in health and disease – Nature Reviews Nephrology

  • Gall, J. G. The origin of in situ hybridization – a personal history. Methods 98, 4–9 (2016).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Tian, L., Chen, F. & Macosko, E. Z. The expanding vistas of spatial transcriptomics. Nat. Biotechnol. 41, 773–782 (2023).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Lopez, R. et al. DestVI identifies continuums of cell types in spatial transcriptomics data. Nat. Biotechnol. 40, 1360–1369 (2022).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Li, H. et al. A comprehensive benchmarking with practical guidelines for cellular deconvolution of spatial transcriptomics. Nat. Commun. 14, 1548 (2023).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Longo, S. K., Guo, M. G., Ji, A. L. & Khavari, P. A. Integrating single-cell and spatial transcriptomics to elucidate intercellular tissue dynamics. Nat. Rev. Genet. 22, 627–644 (2021).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Dries, R. et al. Advances in spatial transcriptomic data analysis. Genome Res. 31, 1706–1718 (2021).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Jain, S. et al. Advances and prospects for the Human BioMolecular Atlas Program (HuBMAP). Nat. Cell Biol. 25, 1089–1100 (2023).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Rozenblatt-Rosen, O., Stubbington, M. J. T., Regev, A. & Teichmann, S. A. The Human Cell Atlas: from vision to reality. Nature 550, 451–453 (2017).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Rozenblatt-Rosen, O. et al. The Human Tumor Atlas Network: charting tumor transitions across space and time at single-cell resolution. Cell 181, 236–249 (2020).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • de Boer, I. H. et al. Rationale and design of the Kidney Precision Medicine Project. Kidney Int. 99, 498–510 (2021).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • HuBMAP Consortium. The human body at cellular resolution: the NIH human biomolecular atlas program. Nature 574, 187–192 (2019).

    Article 
    CAS 

    Google Scholar
     

  • SenNet, C. NIH SenNet Consortium to map senescent cells throughout the human lifespan to understand physiological health. Nat. Aging 2, 1090–1100 (2022).

    Article 

    Google Scholar
     

  • Oxburgh, L. et al. (Re)Building a Kidney. J. Am. Soc. Nephrol. 28, 1370–1378 (2017).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Regev, A. et al. The Human Cell Atlas. Elife 6, e27041 (2017).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Stahl, P. L. et al. Visualization and analysis of gene expression in tissue sections by spatial transcriptomics. Science 353, 78–82 (2016).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Rodriques, S. G. et al. Slide-seq: a scalable technology for measuring genome-wide expression at high spatial resolution. Science 363, 1463–1467 (2019).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Chen, A. et al. Spatiotemporal transcriptomic atlas of mouse organogenesis using DNA nanoball-patterned arrays. Cell 185, 1777–1792.e21 (2022).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Lake, B. B. et al. An atlas of healthy and injured cell states and niches in the human kidney. Nature 619, 585–594 (2023).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Fan, Y. et al. Expansion spatial transcriptomics. Nat. Methods 20, 1179–1182 (2023).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Wirth, J. et al. Spatial transcriptomics using multiplexed deterministic barcoding in tissue. Nat. Commun. 14, 1523 (2023).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Salem, F. et al. The spatially resolved transcriptional profile of acute T cell-mediated rejection in a kidney allograft. Kidney Int. 101, 131–136 (2022).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Srivatsan, S. R. et al. Embryo-scale, single-cell spatial transcriptomics. Science 373, 111–117 (2021).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Lee, Y. et al. XYZeq: spatially resolved single-cell RNA sequencing reveals expression heterogeneity in the tumor microenvironment. Sci. Adv. 7, eabg4755 (2021).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Nguyen, H. Q. et al. 3D mapping and accelerated super-resolution imaging of the human genome using in situ sequencing. Nat. Methods 17, 822–832 (2020).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Lee, J. H. et al. Fluorescent in situ sequencing (FISSEQ) of RNA for gene expression profiling in intact cells and tissues. Nat. Protoc. 10, 442–458 (2015).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Wang, X. et al. Three-dimensional intact-tissue sequencing of single-cell transcriptional states. Science 361, eaat5691 (2018).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Biancalani, T. et al. Deep learning and alignment of spatially resolved single-cell transcriptomes with Tangram. Nat. Methods 18, 1352–1362 (2021).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Chen, K. H., Boettiger, A. N., Moffitt, J. R., Wang, S. & Zhuang, X. RNA imaging. Spatially resolved, highly multiplexed RNA profiling in single cells. Science 348, aaa6090 (2015).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • He, S. et al. High-plex imaging of RNA and proteins at subcellular resolution in fixed tissue by spatial molecular imaging. Nat. Biotechnol. 40, 1794–1806 (2022).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Ke, R. et al. In situ sequencing for RNA analysis in preserved tissue and cells. Nat. Methods 10, 857–860 (2013).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Groiss, S. et al. Highly resolved spatial transcriptomics for detection of rare events in cells. Preprint at bioRxiv, https://doi.org/10.1101/2021.10.11.463936 (2021).

  • Eng, C. L. et al. Transcriptome-scale super-resolved imaging in tissues by RNA seqFISH. Nature 568, 235–239 (2019).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Andersson, A. et al. Single-cell and spatial transcriptomics enables probabilistic inference of cell type topography. Commun. Biol. 3, 565 (2020).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Hao, Y. et al. Integrated analysis of multimodal single-cell data. Cell 184, 3573–3587.e29 (2021).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Melo Ferreira, R. et al. Integration of spatial and single cell transcriptomics localizes epithelial-immune cross-talk in kidney injury. JCI Insight 6, e147703 (2021).

    Article 
    PubMed 

    Google Scholar
     

  • Brbic, M. et al. Annotation of spatially resolved single-cell data with STELLAR. Nat. Methods 19, 1411–1418 (2022).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Wei, R. et al. Spatial charting of single-cell transcriptomes in tissues. Nat. Biotechnol. 40, 1190–1199 (2022).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Elosua-Bayes, M., Nieto, P., Mereu, E., Gut, I. & Heyn, H. SPOTlight: seeded NMF regression to deconvolute spatial transcriptomics spots with single-cell transcriptomes. Nucleic Acids Res. 49, e50 (2021).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Cable, D. M. et al. Robust decomposition of cell type mixtures in spatial transcriptomics. Nat. Biotechnol. 40, 517–526 (2022).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Li, B. et al. Benchmarking spatial and single-cell transcriptomics integration methods for transcript distribution prediction and cell type deconvolution. Nat. Methods 19, 662–670 (2022).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Melo Ferreira, R., Freije, B. J. & Eadon, M. T. Deconvolution tactics and normalization in renal spatial transcriptomics. Front. Physiol. 12, 812947 (2021).

    Article 
    PubMed 

    Google Scholar
     

  • Zeng, Z., Li, Y., Li, Y. & Luo, Y. Statistical and machine learning methods for spatially resolved transcriptomics data analysis. Genome Biol. 23, 83 (2022).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Qian, J. et al. Reconstruction of the cell pseudo-space from single-cell RNA sequencing data with scSpace. Nat. Commun. 14, 2484 (2023).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Wang, J. et al. Dimension-agnostic and granularity-based spatially variable gene identification using BSP. Nat. Commun. 14, 7367 (2023).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Keller, M. S. et al. Vitessce: a framework for integrative visualization of multimodal and spatially-resolved single-cell data. Preprint at OSF Preprints, https://doi.org/10.31219/osf.io/y8thv (2023).

  • Palla, G. et al. Squidpy: a scalable framework for spatial omics analysis. Nat. Methods 19, 171–178 (2022).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Dries, R. et al. Giotto: a toolbox for integrative analysis and visualization of spatial expression data. Genome Biol. 22, 78 (2021).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Winfree, S. et al. Integrated cytometry with machine learning applied to high-content imaging of human kidney tissue for in situ cell classification and neighborhood analysis. Lab. Invest. 103, 100104 (2023).

    Article 
    PubMed 

    Google Scholar
     

  • Li, Z., Song, T., Yong, J. & Kuang, R. Imputation of spatially-resolved transcriptomes by graph-regularized tensor completion. PLoS Comput. Biol. 17, e1008218 (2021).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Park, J. et al. Cell segmentation-free inference of cell types from in situ transcriptomics data. Nat. Commun. 12, 3545 (2021).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Zhang, Y. et al. Reference-based cell type matching of in situ image-based spatial transcriptomics data on primary visual cortex of mouse brain. Sci. Rep. 13, 9567 (2023).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Liu, Y. et al. High-plex protein and whole transcriptome co-mapping at cellular resolution with spatial CITE-seq. Nat. Biotechnol. 41, 1405–1409 (2023).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Canela, V. H. et al. A spatially anchored transcriptomic atlas of the human kidney papilla identifies significant immune injury in patients with stone disease. Nat. Commun. 14, 4140 (2023).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Deng, Y. et al. Spatial profiling of chromatin accessibility in mouse and human tissues. Nature 609, 375–383 (2022).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Llorens-Bobadilla, E. et al. Solid-phase capture and profiling of open chromatin by spatial ATAC. Nat. Biotechnol. 41, 1085–1088 (2023).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Chen, S., Lake, B. B. & Zhang, K. High-throughput sequencing of the transcriptome and chromatin accessibility in the same cell. Nat. Biotechnol. 37, 1452–1457 (2019).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Gisch, D. L. et al. The chromatin landscape of healthy and injured cell types in the human kidney. Nat. Commun. 15, 433 (2024).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Lucarelli, N. et al. Correlating deep learning-based automated reference kidney histomorphometry with patient demographics and creatinine. Kidney360 4, 1726–1737 (2023).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Shickel, B. et al. Spatially aware transformer networks for contextual prediction of diabetic nephropathy progression from whole slide images. Proc. SPIE Int. Soc. Opt. Eng. 12471, 124710K (2023).

    PubMed 
    PubMed Central 

    Google Scholar
     

  • Zheng, Y. et al. Deep-learning-driven quantification of interstitial fibrosis in digitized kidney biopsies. Am. J. Pathol. 191, 1442–1453 (2021).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • FUSION: Functional Unit State Identification and Navigation with WSI. Welcome to FUSION! fusion, http://fusion.hubmapconsortium.org/ (2023).

  • Ferkowicz, M. J. et al. Molecular signatures of glomerular neovascularization in a patient with diabetic kidney disease. Clin. J. Am. Soc. Nephrol. 19, 266–275 (2023).

    Article 
    PubMed 

    Google Scholar
     

  • Janosevic, D. et al. The orchestrated cellular and molecular responses of the kidney to endotoxin define a precise sepsis timeline. Elife 10, e62270 (2021).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Cheung, M. D. et al. Resident macrophage subpopulations occupy distinct microenvironments in the kidney. JCI Insight 7, e161078 (2022).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Wang, Z. et al. Integrated single-nucleus sequencing and spatial architecture analysis identified distinct injured-proximal tubular types in calculi rats. Cell Biosci. 13, 92 (2023).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Dixon, E. E., Wu, H., Muto, Y., Wilson, P. C. & Humphreys, B. D. Spatially resolved transcriptomic analysis of acute kidney injury in a female murine model. J. Am. Soc. Nephrol. 33, 279–289 (2022).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Wu, H. et al. High resolution spatial profiling of kidney injury and repair using RNA hybridization-based in situ sequencing. Nat. Commun. 15, 1396 (2024).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Kayhan, M. et al. Intrinsic TGF-β signaling attenuates proximal tubule mitochondrial injury and inflammation in chronic kidney disease. Nat. Commun. 14, 3236 (2023).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Onoda, N. et al. Spatial and single-cell transcriptome analysis reveals changes in gene expression in response to drug perturbation in rat kidney. DNA Res 29, dsac007 (2022).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Sanchez-Ferras, O. et al. A coordinated progression of progenitor cell states initiates urinary tract development. Nat. Commun. 12, 2627 (2021).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Hodgin, J. B. et al. Quantification of glomerular structural lesions: associations with clinical outcomes and transcriptomic profiles in nephrotic syndrome. Am. J. Kidney Dis. 79, 807–819.e1 (2022).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Mariani, L. H. et al. CureGN study rationale, design, and methods: establishing a large prospective observational study of glomerular disease. Am. J. Kidney Dis. 73, 218–229 (2019).

    Article 
    PubMed 

    Google Scholar
     

  • Townsend, R. R. et al. Rationale and design of the Transformative Research in Diabetic Nephropathy (TRIDENT) Study. Kidney Int. 97, 10–13 (2020).

    Article 
    PubMed 

    Google Scholar
     

  • Hickey, J. W. et al. Organization of the human intestine at single-cell resolution. Nature 619, 572–584 (2023).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Hunter, M. V., Moncada, R., Weiss, J. M., Yanai, I. & White, R. M. Spatially resolved transcriptomics reveals the architecture of the tumor-microenvironment interface. Nat. Commun. 12, 6278 (2021).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Lake, B. B. et al. A single-nucleus RNA-sequencing pipeline to decipher the molecular anatomy and pathophysiology of human kidneys. Nat. Commun. 10, 2832 (2019).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Chen, D. et al. Single-cell RNA-seq with spatial transcriptomics to create an atlas of human diabetic kidney disease. Faseb J. 37, e22938 (2023).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Abedini, A. et al. Spatially resolved human kidney multi-omics single cell atlas highlights the key role of the fibrotic microenvironment in kidney disease progression. Preprint at bioRxiv, https://doi.org/10.1101/2022.10.24.513598 (2024).

  • Marshall, J. L. et al. High-resolution Slide-seqV2 spatial transcriptomics enables discovery of disease-specific cell neighborhoods and pathways. iScience 25, 104097 (2022).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Raghubar, A. M. et al. Spatially resolved transcriptomes of mammalian kidneys illustrate the molecular complexity and interactions of functional nephron segments. Front. Med. 9, 873923 (2022).

    Article 

    Google Scholar
     

  • Cheung, M. D. et al. Spatiotemporal immune atlas of a clinical-grade gene-edited pig-to-human kidney xenotransplant. Nat. Commun. 15, 3140 (2024).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Zimmerman, S. M. et al. Spatially resolved whole transcriptome profiling in human and mouse tissue using digital spatial profiling. Genome Res. 32, 1892–1905 (2022).

    PubMed 
    PubMed Central 

    Google Scholar
     

  • El-Achkar, T. M. et al. A multimodal and integrated approach to interrogate human kidney biopsies with rigor and reproducibility: guidelines from the Kidney Precision Medicine Project. Physiol. Genomics 53, 1–11 (2021).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Liu, Y. et al. High-spatial-resolution multi-omics sequencing via deterministic barcoding in tissue. Cell 183, 1665–1681.e18 (2020).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Long, Y. et al. Spatially informed clustering, integration, and deconvolution of spatial transcriptomics with GraphST. Nat. Commun. 14, 1155 (2023).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Korsunsky, I. et al. Fast, sensitive and accurate integration of single-cell data with Harmony. Nat. Methods 16, 1289–1296 (2019).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Fischer, D. S., Schaar, A. C. & Theis, F. J. Modeling intercellular communication in tissues using spatial graphs of cells. Nat. Biotechnol. 41, 332–336 (2023).

    Article 
    CAS 
    PubMed 

    Google Scholar