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Review | Open Access

Exploring machine learning strategies for single-cell transcriptomic analysis in wound healing

Jianzhou Cui1,2,3,‡( ), Mei Wang4,‡, Chenshi Lin1,2,3, Xu Xu5, Zhenqing Zhang6( )
Immunology Translational Research Program, Yong Loo Lin School of Medicine, National University of Singapore, 28 Medical Drive, Singapore, 117456, Singapore
Immunology Program, Life Sciences Institute, National University of Singapore, 28 Medical Drive, Singapore, 117456, Singapore
NUS-Cambridge Immunophenotyping Centre, National University of Singapore, 28 Medical Drive, Singapore, 117456, Singapore
Key Laboratory of Basic Pharmacology of Ministry of Education, Joint International Research Laboratory of Ethnomedicine of Ministry of Education, Zunyi Medical University,1, Xiaoyuan Road, Zunyi, 563000, China
Shenzhen Key Laboratory of Marine Bioresources and Ecology, College of Life Sciences and Oceanography, Shenzhen University, 1066, Xueyuan Road, Shenzhen, 518060, China
College of Pharmaceutical Sciences and Jiangsu Key Laboratory of Neuropsychiatric Diseases, Soochow University, 199, Renai Road, Suzhou, 215021, China

‡Jianzhou Cui and Mei Wang contributed equally.

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Highlights

• Machine learning algorithms, particularly deep learning, have significantly enhanced the analysis of scRNA-seq data in wound healing research, improving critical tasks such as dimensionality reduction, cell clustering, and trajectory inference.

• Single-cell analyses have revealed remarkable fibroblast heterogeneity, identifying distinct subpopulations involved in scar formation and regenerative healing.

• Integration of scRNA-seq with machine learning has provided insights into immune cell function, elucidating the roles of macrophages and other immune cells in orchestrating both inflammatory responses and tissue repair during wound healing.

Abstract

Wound healing is a highly orchestrated, multiphase process that involves various cell types and molecular pathways. Recent advances in single-cell transcriptomics and machine learning have provided unprecedented insights into the complexity of this process, enabling the identification of novel cellular subpopulations and molecular mechanisms underlying tissue repair. In particular, single-cell RNA sequencing (scRNA-seq) has revealed significant cellular heterogeneity, especially within fibroblast populations, and has provided valuable information on immune cell dynamics during healing. Machine learning algorithms have enhanced data analysis by improving cell clustering, dimensionality reduction, and trajectory inference, leading to a better understanding of wound healing at the single-cell level. This review synthesizes the latest findings on the application of scRNA-seq and machine learning in wound healing research, with a focus on fibroblast diversity, immune responses, and spatial organization of cells. The integration of these technologies has the potential to revolutionize therapeutic strategies for chronic wounds, fibrosis, and tissue regeneration, offering new opportunities for precision medicine. By combining computational approaches with biological insights, this review highlights the transformative impact of scRNA-seq and machine learning on wound healing research.

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Burns & Trauma
Article number: tkaf032

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Cite this article:
Cui J, Wang M, Lin C, et al. Exploring machine learning strategies for single-cell transcriptomic analysis in wound healing. Burns & Trauma, 2025, 13(7): tkaf032. https://doi.org/10.1093/burnst/tkaf032

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Received: 06 September 2024
Revised: 27 April 2025
Accepted: 12 May 2025
Published: 13 May 2025
© The Author(s) 2025. Published by Oxford University Press.

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.