Li Wei,Tu Beilin,Li Xiaoqian,et al.The changes and interactions of key cell subpopulations in keloids before and after radiotherapy[J].Chinese Journal of Radiological Medicine and Protection,2024,44(11):917-923
The changes and interactions of key cell subpopulations in keloids before and after radiotherapy
Received:November 23, 2023  
DOI:10.3760/cma.j.cn112271-20231123-00171
KeyWords:Single cell RNA sequencing (scRNA-Seq)  Keloid  Radiotherapy  Fibroblasts  Macrophages
FundProject:国家自然科学基金(82073477);四川省科技计划项目(2022JDJQ0051,2023NSFSC0648)
Author NameAffiliationE-mail
Li Wei Department of Plastic and Burn Surgery, West China Hospital, Sichuan University, Chengdu 610041, China  
Tu Beilin Department of Plastic and Burn Surgery, West China Hospital, Sichuan University, Chengdu 610041, China  
Li Xiaoqian West China School of Basic Medical Sciences & Forensic Medicine, Sichuan University, Chengdu 610041, China  
Xu Xuewen Department of Plastic and Burn Surgery, West China Hospital, Sichuan University, Chengdu 610041, China  
Xiao Haitao Department of Plastic and Burn Surgery, West China Hospital, Sichuan University, Chengdu 610041, China  
Zhang Yange Department of Plastic and Burn Surgery, West China Hospital, Sichuan University, Chengdu 610041, China  
Zhang Shuyu West China School of Basic Medical Sciences & Forensic Medicine, Sichuan University, Chengdu 610041, China zhangshuyu@scu.edu.cn 
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Abstract::
      Objective To explore the heterogeneity among keloids before and after radiotherapy and identify the changes of key cell subpopulations and their interactions utilizing single cell RNA sequencing technology. Methods Four patients provided a total of 12 samples, each consisting of keloid tissue before and after radiotherapy and the normal skin tissue adjacent to the untreated keloid. The keloid was divided into left and right sides from the midline, and the left-side keloid was fractionally irradiated with 20 Gy electron beam in total in 4 consecutive days. The right-side keloid was irradiated with 10 Gy in 2 fractions before surgery and 10 Gy in 2 fractions after surgery. Results A total of 25 573 fibroblasts were analyzed and categorized into nine subgroups (fibroblasts 1-9). The proportion of fibroblast-2 increased after radiotherapy (t=4.70, P<0.05). The number of classical monocytes and macrophages increased after radiotherapy, but there was no significant difference due to the shorter time of sample taking at 2 d after radiotherapy (P>0.05). Macrophages (4 723 cells) were further divided into four categories. CellPhoneDB analysis showed that type-3 macrophages interacted significantly more closely with fibroblasts than type-1 and type-2 macrophages. The most prominent signaling pathways for the interactions between type-3 macrophages and major fibroblast subtypes were the collagen signaling pathway and the chemerin signaling pathway. These interactions were more pronounced in the keloid samples after radiotherapy. Conclusions The interactions between type-3 macrophages and fibroblasts (such as fibroblast-2) may serve as an important point for future studies on radio-sensitization of keloids.
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