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Single-Cell Sequencing and Spatial Transcriptomics Reveal Functional Plasticity of Lymphatic Endothelial Cells in Disease

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https://doi.org/10.54963/entu.v16i2.2360
Che, Q., Wang, C., Zheng, S., Zhao, K., & Liu, M. (2026). Single-Cell Sequencing and Spatial Transcriptomics Reveal Functional Plasticity of Lymphatic Endothelial Cells in Disease. ENT Updates, 16(2), 14–26. https://doi.org/10.54963/entu.v16i2.2360
Volume 16 Issue 2 (2026): In Progress
Copyright (c) 2026 Qin Che, Cheng Wang, Shikang Zheng, Kai Zhao, Mingbo Liu
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This work is licensed under a Creative Commons Attribution 4.0 International License.

Authors

  • Qin Che

    Graduate School, Medical School of Chinese PLA, Beijing 100080, China
  • Cheng Wang

    Department of Otolaryngology Head and Neck Surgery, Hainan Hospital of Chinese PLA General Hospital, Sanya 572013, China
  • Shikang Zheng

    Department of Otolaryngology Head and Neck Surgery, Hainan Hospital of Chinese PLA General Hospital, Sanya 572013, China
  • Kai Zhao

    Department of Otolaryngology Head and Neck Surgery, Hainan Hospital of Chinese PLA General Hospital, Sanya 572013, China
  • Mingbo Liu

    Department of Otolaryngology Head and Neck Surgery, Chinese PLA General Hospital, Beijing 100080, China

Received: 14 March 2026; Revised: 30 April 2026; Accepted: 3 June 2026; Published: 8 June 2026

Lymphatic endothelial cells (LECs) have long been viewed as passive conduits that merely maintain tissue fluid homeostasis. But that picture has changed dramatically. Recent advances in single-cell transcriptome sequencing (scRNA-seq) and spatial transcriptomics (ST) have revealed that LECs are highly heterogeneous and remarkably plastic in their functions. This review summarizes the new research results of LECs based on the above two technologies. LECs in normal tissues have multiple types of subpopulations. In the lymph node, there are further sub-regions, such as the subcapsular sinus ceiling/floor LECs, medullary sinus LECs, valve LECs and other special subsets. Each subpopulation performs distinct functions depending on its anatomical location, ranging from lymph drainage and barrier formation to immune regulation, etc. Under pathological conditions such as cancer, chronic inflammation, cardiovascular disease, obesity, and tissue repair, LECs undergo profound transcriptional reprogramming and phenotypic remodeling. They express immune checkpoint molecules, secrete chemokines, and build ligand-receptor interaction networks. In other words, LECs transform from passive structural pipes into active signaling integration centers and immune regulatory hubs. They participate directly in immune response modulation, metastasis promotion or suppression, tissue repair, and fibrosis. These findings have fundamentally redefined the biological role of LECs in the microenvironment. Targeting LECs heterogeneity and their bidirectional cell-cell interaction networks may offer novel stromal-targeted strategies for intervening in tumor lymphatic metastasis, reversing chronic inflammation, and treating cardiovascular diseases.

Keywords:

Lymphatic Endothelial Cell Single-Cell Transcriptome Sequencing Spatial Transcriptomics Functional Plasticity Tumor Microenvironment Chronic Inflammation Cardiovascular Disease Immune Regulation

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