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Single-nucleus RNA sequencing reveals heterogenous microenvironments and specific drug response between cervical squamous cell carcinoma and adenocarcinoma

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WOS体系：
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收录情况： ◇ SCIE

作者：
Lin Shitong[1,2] * ; Sun Yuanhui[4,6] * ; Cao Canhui[2,3] * ; Zhu Zhixian[4,6] * ; Xu Yashi[1,2] ; Liu Binghan[1,2] ; Hu Bai[2,3] ; Peng Ting[2,3] ; Zhi Wenhua[2,3] ; Xu Miaochun[1,2] ; Ding Wencheng[2,3] ; Ren Fang[5] ; Ma Ding[2,3,*3] ; Li Guoliang[4,6,*2] ; Wu Peng[1,2,*1] ;
单位： [1]Department of Obstetrics and Gynecology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology,1277 Jiefang Avenue, Wuhan, Hubei, 430022, PR China [2]Cancer Biology Research Center (Key Laboratory of the Ministry of Education),Tongji Hospital,Tongji Medical College,HuazhongUniversity of Science and Technology,Wuhan,Hubei,China [3]Department of Gynecologic Oncology,Tongji Hospital,Tongji Medical College,Huazhong University of Science and Technology,Wuhan,Hubei,China [4]National Key Laboratory of Crop Genetic Improvement, Huazhong Agricultural University, Wuhan, 430070, China [5]Department of Gynecology, First Affiliated Hospital of Zhengzhou University, Zhengzhou, China [6]Agricultural Bioinformatics Key Laboratory of Hubei Province, Hubei Engineering Technology Research Center of Agricultural Big Data,College of Informatics, Huazhong Agricultural University, Wuhan, 430070, China
出处：
DOI： 10.1016/j.ebiom.2023.104846
ISSN：

关键词： snRNA-seq CSCC CAde Microenvironments Drug response

摘要：
Cervical squamous cell carcinoma (CSCC) and adenocarcinoma (CAde) are two major pathological types of cervical cancer (CC), but their high-resolution heterogeneity of tumor and immune microenvironment remains elusive.Here, we performed single-nucleus RNA sequencing (snRNA-seq) from five CSCC and three CAde samples, and systematically outlined their specific transcriptome atlas.We found CD8+ T cells in CSCC were more cytotoxic but lower exhausted compared to those in CAde, and phagocytic MRC1+ macrophages were specifically enriched in CSCC. Interestingly, we discovered that pro-tumoral cancer-associated myofibroblasts (myoCAFs) and cancer-associated vascular-fibroblasts (vCAFs) were more abundant in CSCC, and further verified their pro-metastatic roles in vitro. Furthermore, we also identified some specific chemotherapy drugs for CSCC (Dasatinib and Doramapimod) and CAde (Pyrimethamine and Lapatinib) by revealing their heterogeneity in transcriptomic profiles of malignant epithelial cells, and further verified their specific sensitivity in cell lines and constructed CC-derived organoids. Cell-cell communication networks revealed that the pathways of NRG1-ERBB2, and FN1-ITAG3 were specific for CAde and CSCC, respectively, which may partly explain the specificities of identified chemotherapy drugs.Our study described the immune heterogeneity and specific cellular interactions between CSCC and CAde, which could provide insights for uncovering pathogenesis and designing personalized treatment.National Key R&D Program of China (2021YFC2701201), National Natural Science Foundation of China (82072895, 82141106, 82103134, 81903114).Copyright © 2023 The Author(s). Published by Elsevier B.V. All rights reserved.

基金：
National Key R&D Program of China (2021YFC2701201), National Natural Science Foundation of China(82072895, 82141106, 82103134, 81903114)
语种：
外文
WOS：
PubmedID：
中科院(CAS)分区：
出版当年[2022]版：
大类 | 1 区 医学
小类 | 1 区 医学：研究与实验
最新[2025]版：
大类 | 1 区 医学
小类 | 1 区 医学：研究与实验
JCR分区：
出版当年[2021]版：
Q1 MEDICINE, RESEARCH & EXPERIMENTAL
最新[2024]版：
Q1 MEDICINE, RESEARCH & EXPERIMENTAL

影响因子： 最新[2024版] 最新五年平均 出版当年[2021版] 出版当年五年平均 出版前一年[2020版] 出版后一年[2022版]

第一作者：
第一作者单位： [1]Department of Obstetrics and Gynecology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology,1277 Jiefang Avenue, Wuhan, Hubei, 430022, PR China [2]Cancer Biology Research Center (Key Laboratory of the Ministry of Education),Tongji Hospital,Tongji Medical College,HuazhongUniversity of Science and Technology,Wuhan,Hubei,China
共同第一作者：
通讯作者：
通讯机构： [1]Department of Obstetrics and Gynecology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology,1277 Jiefang Avenue, Wuhan, Hubei, 430022, PR China [2]Cancer Biology Research Center (Key Laboratory of the Ministry of Education),Tongji Hospital,Tongji Medical College,HuazhongUniversity of Science and Technology,Wuhan,Hubei,China [3]Department of Gynecologic Oncology,Tongji Hospital,Tongji Medical College,Huazhong University of Science and Technology,Wuhan,Hubei,China [4]National Key Laboratory of Crop Genetic Improvement, Huazhong Agricultural University, Wuhan, 430070, China [6]Agricultural Bioinformatics Key Laboratory of Hubei Province, Hubei Engineering Technology Research Center of Agricultural Big Data,College of Informatics, Huazhong Agricultural University, Wuhan, 430070, China [*1]Department of Obstetrics and Gynecology, Union Hospital, Tongji Medical College, Huazhong University of Science andTechnology, 1277 Jiefang Avenue, Wuhan, Hubei, 430022, PR China [*2]National Key Laboratory of Crop Genetic Improvement, Huazhong Agricultural University, Wuhan, 430070, China [*3]Cancer Biology Research Center (Key Laboratory of the Ministry of Education),Tongji Hospital,Tongji Medical College,Huazhong University of Science and Technology,Wuhan,Hubei,China
推荐引用方式(GB/T 7714)：
Lin Shitong,Sun Yuanhui,Cao Canhui,et al.Single-nucleus RNA sequencing reveals heterogenous microenvironments and specific drug response between cervical squamous cell carcinoma and adenocarcinoma[J].EBIOMEDICINE.2023,97:doi:10.1016/j.ebiom.2023.104846.
APA：
Lin Shitong,Sun Yuanhui,Cao Canhui,Zhu Zhixian,Xu Yashi...&Wu Peng.(2023).Single-nucleus RNA sequencing reveals heterogenous microenvironments and specific drug response between cervical squamous cell carcinoma and adenocarcinoma.EBIOMEDICINE,97,
MLA：
Lin Shitong,et al."Single-nucleus RNA sequencing reveals heterogenous microenvironments and specific drug response between cervical squamous cell carcinoma and adenocarcinoma".EBIOMEDICINE 97.(2023)

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