IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v16y2025i1d10.1038_s41467-025-58989-8.html
   My bibliography  Save this article

Combining spatial transcriptomics with tissue morphology

Author

Listed:
  • Eduard Chelebian

    (Uppsala University)

  • Christophe Avenel

    (Uppsala University)

  • Carolina Wählby

    (Uppsala University)

Abstract

Spatial transcriptomics has transformed our understanding of tissue architecture by preserving the spatial context of gene expression patterns. Simultaneously, advances in imaging AI have enabled extraction of morphological features describing the tissue. This review introduces a framework for categorizing methods that combine spatial transcriptomics with tissue morphology, focusing on either translating or integrating morphological features into spatial transcriptomics. Translation involves using morphology to predict gene expression, creating super-resolution maps or inferring genetic information from H&E-stained samples. Integration enriches spatial transcriptomics by identifying morphological features that complement gene expression. We also explore learning strategies and future directions for this emerging field.

Suggested Citation

  • Eduard Chelebian & Christophe Avenel & Carolina Wählby, 2025. "Combining spatial transcriptomics with tissue morphology," Nature Communications, Nature, vol. 16(1), pages 1-13, December.
    • Handle: RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-58989-8
    DOI: 10.1038/s41467-025-58989-8
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-025-58989-8
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-025-58989-8?utm_source=ideas
    LibKey link: if access is restricted and if your library uses this service, LibKey will redirect you to where you can use your library subscription to access this item
    ---><---

    References listed on IDEAS

    as
    1. Tongtong Zhao & Zachary D. Chiang & Julia W. Morriss & Lindsay M. LaFave & Evan M. Murray & Isabella Del Priore & Kevin Meli & Caleb A. Lareau & Naeem M. Nadaf & Jilong Li & Andrew S. Earl & Evan Z. M, 2022. "Spatial genomics enables multi-modal study of clonal heterogeneity in tissues," Nature, Nature, vol. 601(7891), pages 85-91, January.
    2. Amanda Janesick & Robert Shelansky & Andrew D. Gottscho & Florian Wagner & Stephen R. Williams & Morgane Rouault & Ghezal Beliakoff & Carolyn A. Morrison & Michelli F. Oliveira & Jordan T. Sicherman &, 2023. "High resolution mapping of the tumor microenvironment using integrated single-cell, spatial and in situ analysis," Nature Communications, Nature, vol. 14(1), pages 1-15, December.
    3. Duy Pham & Xiao Tan & Brad Balderson & Jun Xu & Laura F. Grice & Sohye Yoon & Emily F. Willis & Minh Tran & Pui Yeng Lam & Arti Raghubar & Priyakshi Kalita-de Croft & Sunil Lakhani & Jana Vukovic & Ma, 2023. "Robust mapping of spatiotemporal trajectories and cell–cell interactions in healthy and diseased tissues," Nature Communications, Nature, vol. 14(1), pages 1-25, December.
    4. Michael Moor & Oishi Banerjee & Zahra Shakeri Hossein Abad & Harlan M. Krumholz & Jure Leskovec & Eric J. Topol & Pranav Rajpurkar, 2023. "Foundation models for generalist medical artificial intelligence," Nature, Nature, vol. 616(7956), pages 259-265, April.
    5. Artem Lomakin & Jessica Svedlund & Carina Strell & Milana Gataric & Artem Shmatko & Gleb Rukhovich & Jun Sung Park & Young Seok Ju & Stefan Dentro & Vitalii Kleshchevnikov & Vasyl Vaskivskyi & Tong Li, 2022. "Spatial genomics maps the structure, nature and evolution of cancer clones," Nature, Nature, vol. 611(7936), pages 594-602, November.
    6. Lulu Shang & Xiang Zhou, 2022. "Spatially aware dimension reduction for spatial transcriptomics," Nature Communications, Nature, vol. 13(1), pages 1-22, December.
    7. Chuhan Wang & Adam S. Chan & Xiaohang Fu & Shila Ghazanfar & Jinman Kim & Ellis Patrick & Jean Y. H. Yang, 2025. "Benchmarking the translational potential of spatial gene expression prediction from histology," Nature Communications, Nature, vol. 16(1), pages 1-17, December.
    8. Andrew Erickson & Mengxiao He & Emelie Berglund & Maja Marklund & Reza Mirzazadeh & Niklas Schultz & Linda Kvastad & Alma Andersson & Ludvig Bergenstråhle & Joseph Bergenstråhle & Ludvig Larsson & Lei, 2022. "Spatially resolved clonal copy number alterations in benign and malignant tissue," Nature, Nature, vol. 608(7922), pages 360-367, August.
    9. Xiaohang Fu & Yingxin Lin & David M. Lin & Daniel Mechtersheimer & Chuhan Wang & Farhan Ameen & Shila Ghazanfar & Ellis Patrick & Jinman Kim & Jean Y. H. Yang, 2024. "BIDCell: Biologically-informed self-supervised learning for segmentation of subcellular spatial transcriptomics data," Nature Communications, Nature, vol. 15(1), pages 1-17, December.
    10. Chee-Huat Linus Eng & Michael Lawson & Qian Zhu & Ruben Dries & Noushin Koulena & Yodai Takei & Jina Yun & Christopher Cronin & Christoph Karp & Guo-Cheng Yuan & Long Cai, 2019. "Transcriptome-scale super-resolved imaging in tissues by RNA seqFISH+," Nature, Nature, vol. 568(7751), pages 235-239, April.
    11. Lawrence Hubert & Phipps Arabie, 1985. "Comparing partitions," Journal of Classification, Springer;The Classification Society, vol. 2(1), pages 193-218, December.
    12. Anjali Rao & Dalia Barkley & Gustavo S. França & Itai Yanai, 2021. "Exploring tissue architecture using spatial transcriptomics," Nature, Nature, vol. 596(7871), pages 211-220, August.
    13. Hanwen Xu & Naoto Usuyama & Jaspreet Bagga & Sheng Zhang & Rajesh Rao & Tristan Naumann & Cliff Wong & Zelalem Gero & Javier González & Yu Gu & Yanbo Xu & Mu Wei & Wenhui Wang & Shuming Ma & Furu Wei , 2024. "A whole-slide foundation model for digital pathology from real-world data," Nature, Nature, vol. 630(8015), pages 181-188, June.
    Full references (including those not matched with items on IDEAS)

    Most related items

    These are the items that most often cite the same works as this one and are cited by the same works as this one.
    1. Yuchen Liang & Guowei Shi & Runlin Cai & Yuchen Yuan & Ziying Xie & Long Yu & Yingjian Huang & Qian Shi & Lizhe Wang & Jun Li & Zhonghui Tang, 2024. "PROST: quantitative identification of spatially variable genes and domain detection in spatial transcriptomics," Nature Communications, Nature, vol. 15(1), pages 1-17, December.
    2. Bohan Li & Feng Bao & Yimin Hou & Fengji Li & Hongjue Li & Yue Deng & Qionghai Dai, 2024. "Tissue characterization at an enhanced resolution across spatial omics platforms with deep generative model," Nature Communications, Nature, vol. 15(1), pages 1-16, December.
    3. Wei Liu & Xu Liao & Ziye Luo & Yi Yang & Mai Chan Lau & Yuling Jiao & Xingjie Shi & Weiwei Zhai & Hongkai Ji & Joe Yeong & Jin Liu, 2023. "Probabilistic embedding, clustering, and alignment for integrating spatial transcriptomics data with PRECAST," Nature Communications, Nature, vol. 14(1), pages 1-18, December.
    4. Lulu Shang & Xiang Zhou, 2022. "Spatially aware dimension reduction for spatial transcriptomics," Nature Communications, Nature, vol. 13(1), pages 1-22, December.
    5. Zhiyuan Yuan, 2024. "MENDER: fast and scalable tissue structure identification in spatial omics data," Nature Communications, Nature, vol. 15(1), pages 1-17, December.
    6. Jingyang Qian & Hudong Bao & Xin Shao & Yin Fang & Jie Liao & Zhuo Chen & Chengyu Li & Wenbo Guo & Yining Hu & Anyao Li & Yue Yao & Xiaohui Fan & Yiyu Cheng, 2024. "Simulating multiple variability in spatially resolved transcriptomics with scCube," Nature Communications, Nature, vol. 15(1), pages 1-21, December.
    7. Qingnan Liang & Yuefan Huang & Shan He & Ken Chen, 2023. "Pathway centric analysis for single-cell RNA-seq and spatial transcriptomics data with GSDensity," Nature Communications, Nature, vol. 14(1), pages 1-17, December.
    8. Yuyao Liu & Zhen Li & Xiaoyang Chen & Xuejian Cui & Zijing Gao & Rui Jiang, 2025. "INSTINCT: Multi-sample integration of spatial chromatin accessibility sequencing data via stochastic domain translation," Nature Communications, Nature, vol. 16(1), pages 1-23, December.
    9. Johannes Wirth & Nina Huber & Kelvin Yin & Sophie Brood & Simon Chang & Celia P. Martinez-Jimenez & Matthias Meier, 2023. "Spatial transcriptomics using multiplexed deterministic barcoding in tissue," Nature Communications, Nature, vol. 14(1), pages 1-15, December.
    10. Arezou Rahimi & Luis A. Vale-Silva & Maria Fälth Savitski & Jovan Tanevski & Julio Saez-Rodriguez, 2024. "DOT: a flexible multi-objective optimization framework for transferring features across single-cell and spatial omics," Nature Communications, Nature, vol. 15(1), pages 1-15, December.
    11. Wenyi Yang & Pingping Wang & Shouping Xu & Tao Wang & Meng Luo & Yideng Cai & Chang Xu & Guangfu Xue & Jinhao Que & Qian Ding & Xiyun Jin & Yuexin Yang & Fenglan Pang & Boran Pang & Yi Lin & Huan Nie , 2024. "Deciphering cell–cell communication at single-cell resolution for spatial transcriptomics with subgraph-based graph attention network," Nature Communications, Nature, vol. 15(1), pages 1-18, December.
    12. Shuangsang Fang & Mengyang Xu & Lei Cao & Xiaobin Liu & Marija Bezulj & Liwei Tan & Zhiyuan Yuan & Yao Li & Tianyi Xia & Longyu Guo & Vladimir Kovacevic & Junhou Hui & Lidong Guo & Chao Liu & Mengnan , 2025. "Stereopy: modeling comparative and spatiotemporal cellular heterogeneity via multi-sample spatial transcriptomics," Nature Communications, Nature, vol. 16(1), pages 1-19, December.
    13. Rongbo Shen & Lin Liu & Zihan Wu & Ying Zhang & Zhiyuan Yuan & Junfu Guo & Fan Yang & Chao Zhang & Bichao Chen & Wanwan Feng & Chao Liu & Jing Guo & Guozhen Fan & Yong Zhang & Yuxiang Li & Xun Xu & Ji, 2022. "Spatial-ID: a cell typing method for spatially resolved transcriptomics via transfer learning and spatial embedding," Nature Communications, Nature, vol. 13(1), pages 1-17, December.
    14. Zhenzhen Xun & Xinyu Ding & Yao Zhang & Benyan Zhang & Shujing Lai & Duowu Zou & Junke Zheng & Guoqiang Chen & Bing Su & Leng Han & Youqiong Ye, 2023. "Reconstruction of the tumor spatial microenvironment along the malignant-boundary-nonmalignant axis," Nature Communications, Nature, vol. 14(1), pages 1-16, December.
    15. Antti Kiviaho & Sini K. Eerola & Heini M. L. Kallio & Maria K. Andersen & Miina Hoikka & Aliisa M. Tiihonen & Iida Salonen & Xander Spotbeen & Alexander Giesen & Charles T. A. Parker & Sinja Taavitsai, 2024. "Single cell and spatial transcriptomics highlight the interaction of club-like cells with immunosuppressive myeloid cells in prostate cancer," Nature Communications, Nature, vol. 15(1), pages 1-16, December.
    16. Haoyang Li & Yingxin Lin & Wenjia He & Wenkai Han & Xiaopeng Xu & Chencheng Xu & Elva Gao & Hongyu Zhao & Xin Gao, 2024. "SANTO: a coarse-to-fine alignment and stitching method for spatial omics," Nature Communications, Nature, vol. 15(1), pages 1-12, December.
    17. Peng Zhang & Chaofei Gao & Zhuoyu Zhang & Zhiyuan Yuan & Qian Zhang & Ping Zhang & Shiyu Du & Weixun Zhou & Yan Li & Shao Li, 2025. "Systematic inference of super-resolution cell spatial profiles from histology images," Nature Communications, Nature, vol. 16(1), pages 1-21, December.
    18. Kian Kalhor & Chien-Ju Chen & Ho Suk Lee & Matthew Cai & Mahsa Nafisi & Richard Que & Carter R. Palmer & Yixu Yuan & Yida Zhang & Xuwen Li & Jinghui Song & Amanda Knoten & Blue B. Lake & Joseph P. Gau, 2024. "Mapping human tissues with highly multiplexed RNA in situ hybridization," Nature Communications, Nature, vol. 15(1), pages 1-17, December.
    19. Yahui Long & Kok Siong Ang & Mengwei Li & Kian Long Kelvin Chong & Raman Sethi & Chengwei Zhong & Hang Xu & Zhiwei Ong & Karishma Sachaphibulkij & Ao Chen & Li Zeng & Huazhu Fu & Min Wu & Lina Hsiu Ki, 2023. "Spatially informed clustering, integration, and deconvolution of spatial transcriptomics with GraphST," Nature Communications, Nature, vol. 14(1), pages 1-19, December.
    20. Zhixing Zhong & Junchen Hou & Zhixian Yao & Lei Dong & Feng Liu & Junqiu Yue & Tiantian Wu & Junhua Zheng & Gaoliang Ouyang & Chaoyong Yang & Jia Song, 2024. "Domain generalization enables general cancer cell annotation in single-cell and spatial transcriptomics," Nature Communications, Nature, vol. 15(1), pages 1-14, December.

    More about this item

    Statistics

    Access and download statistics

    Corrections

    All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-58989-8. See general information about how to correct material in RePEc.

    If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

    If CitEc recognized a bibliographic reference but did not link an item in RePEc to it, you can help with this form .

    If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

    For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: Sonal Shukla or Springer Nature Abstracting and Indexing (email available below). General contact details of provider: http://www.nature.com .

    Please note that corrections may take a couple of weeks to filter through the various RePEc services.

    IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.