Pan-cancer single-cell analysis reveals the heterogeneity and plasticity of cancer-associated fibroblasts in the tumor microenvironment

Han Luo; Xuyang Xia; Li Bin Huang; Hyunsu An; Minyuan Cao; Gyeong Dae Kim; Hai Ning Chen; Wei Han Zhang; Yang Shu; Xiangyu Kong; Zhixiang Ren; Pei Heng Li; Yang Liu; Huairong Tang; Ronghao Sun; Chao Li; Bing Bai; Weiguo Jia; Yi Liu; Wei Zhang; Li Yang; Yong Peng; Lunzhi Dai; Hongbo Hu; Yong Jiang; Yiguo Hu; Jingqiang Zhu; Hong Jiang; Zhihui Li; Carlos Caulin; Jihwan Park; Heng Xu

doi:10.1038/s41467-022-34395-2

Pan-cancer single-cell analysis reveals the heterogeneity and plasticity of cancer-associated fibroblasts in the tumor microenvironment

Han Luo, Xuyang Xia, Li Bin Huang, Hyunsu An, Minyuan Cao, Gyeong Dae Kim, Hai Ning Chen, Wei Han Zhang, Yang Shu, Xiangyu Kong, Zhixiang Ren, Pei Heng Li, Yang Liu, Huairong Tang, Ronghao Sun, Chao Li, Bing Bai, Weiguo Jia, Yi Liu, Wei ZhangLi Yang, Yong Peng, Lunzhi Dai, Hongbo Hu, Yong Jiang, Yiguo Hu, Jingqiang Zhu, Hong Jiang, Zhihui Li, Carlos Caulin, Jihwan Park, Heng Xu

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Abstract

Cancer-associated fibroblasts (CAFs) are the predominant components of the tumor microenvironment (TME) and influence cancer hallmarks, but without systematic investigation on their ubiquitous characteristics across different cancer types. Here, we perform pan-cancer analysis on 226 samples across 10 solid cancer types to profile the TME at single-cell resolution, illustrating the commonalities/plasticity of heterogenous CAFs. Activation trajectory of the major CAF types is divided into three states, exhibiting distinct interactions with other cell components, and relating to prognosis of immunotherapy. Moreover, minor CAF components represent the alternative origin from other TME components (e.g., endothelia and macrophages). Particularly, the ubiquitous presentation of endothelial-to-mesenchymal transition CAF, which may interact with proximal SPP1⁺ tumor-associated macrophages, is implicated in endothelial-to-mesenchymal transition and survival stratifications. Our study comprehensively profiles the shared characteristics and dynamics of CAFs, and highlight their heterogeneity and plasticity across different cancer types. Browser of integrated pan-cancer single-cell information is available at https://gist-fgl.github.io/sc-caf-atlas/.

Original language	English (US)
Article number	6619
Journal	Nature communications
Volume	13
Issue number	1
DOIs	https://doi.org/10.1038/s41467-022-34395-2
State	Published - Dec 2022
Externally published	Yes

ASJC Scopus subject areas

Chemistry(all)
Biochemistry, Genetics and Molecular Biology(all)
General
Physics and Astronomy(all)

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10.1038/s41467-022-34395-2

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Luo, H., Xia, X., Huang, L. B., An, H., Cao, M., Kim, G. D., Chen, H. N., Zhang, W. H., Shu, Y., Kong, X., Ren, Z., Li, P. H., Liu, Y., Tang, H., Sun, R., Li, C., Bai, B., Jia, W., Liu, Y., ... Xu, H. (2022). Pan-cancer single-cell analysis reveals the heterogeneity and plasticity of cancer-associated fibroblasts in the tumor microenvironment. Nature communications, 13(1), [6619]. https://doi.org/10.1038/s41467-022-34395-2

Luo, H, Xia, X, Huang, LB, An, H, Cao, M, Kim, GD, Chen, HN, Zhang, WH, Shu, Y, Kong, X, Ren, Z, Li, PH, Liu, Y, Tang, H, Sun, R, Li, C, Bai, B, Jia, W, Liu, Y, Zhang, W, Yang, L, Peng, Y, Dai, L, Hu, H, Jiang, Y, Hu, Y, Zhu, J, Jiang, H, Li, Z, Caulin, C, Park, J & Xu, H 2022, 'Pan-cancer single-cell analysis reveals the heterogeneity and plasticity of cancer-associated fibroblasts in the tumor microenvironment', Nature communications, vol. 13, no. 1, 6619. https://doi.org/10.1038/s41467-022-34395-2

@article{ac2dde39e9e34421bea25d44d85222a9,

title = "Pan-cancer single-cell analysis reveals the heterogeneity and plasticity of cancer-associated fibroblasts in the tumor microenvironment",

abstract = "Cancer-associated fibroblasts (CAFs) are the predominant components of the tumor microenvironment (TME) and influence cancer hallmarks, but without systematic investigation on their ubiquitous characteristics across different cancer types. Here, we perform pan-cancer analysis on 226 samples across 10 solid cancer types to profile the TME at single-cell resolution, illustrating the commonalities/plasticity of heterogenous CAFs. Activation trajectory of the major CAF types is divided into three states, exhibiting distinct interactions with other cell components, and relating to prognosis of immunotherapy. Moreover, minor CAF components represent the alternative origin from other TME components (e.g., endothelia and macrophages). Particularly, the ubiquitous presentation of endothelial-to-mesenchymal transition CAF, which may interact with proximal SPP1+ tumor-associated macrophages, is implicated in endothelial-to-mesenchymal transition and survival stratifications. Our study comprehensively profiles the shared characteristics and dynamics of CAFs, and highlight their heterogeneity and plasticity across different cancer types. Browser of integrated pan-cancer single-cell information is available at https://gist-fgl.github.io/sc-caf-atlas/.",

author = "Han Luo and Xuyang Xia and Huang, {Li Bin} and Hyunsu An and Minyuan Cao and Kim, {Gyeong Dae} and Chen, {Hai Ning} and Zhang, {Wei Han} and Yang Shu and Xiangyu Kong and Zhixiang Ren and Li, {Pei Heng} and Yang Liu and Huairong Tang and Ronghao Sun and Chao Li and Bing Bai and Weiguo Jia and Yi Liu and Wei Zhang and Li Yang and Yong Peng and Lunzhi Dai and Hongbo Hu and Yong Jiang and Yiguo Hu and Jingqiang Zhu and Hong Jiang and Zhihui Li and Carlos Caulin and Jihwan Park and Heng Xu",

note = "Funding Information: Appreciates the assistance of Mis. Xinyue Hu in illustration (Fig. ) design and drawing. This study was supported by the National Key R&D Program of China (No. 2021YFA1301203(H.X.), 2018YFC2000305(L.Z.D.)), National Natural Science Foundation of China (82103031(H.L.), 81973408(H.X.), 82272933 (H.L.), 82273445(Y.S.)), International Cooperation Project of Chengdu Municipal Science and Technology Bureau (2020-GH02-00017-HZ(H.L.)), 1.3.5 Project for Disciplines of Excellence, West China Hospital, Sichuan University (No. ZYYC20003(H.X.), ZYJC18035(H.L.), ZYJC18025(Z.H.L.), ZYJC18003(Y.L.), ZYJC18004(H.X.), and ZYYC20007(L.D.)), and the National Research Foundation of Korea funded by the Korean government (2019R1C1C1005403(J.P), 2019R1A4A1028802(J.P), 2021M3H9A2097520(J.P)), Clinical Research Incubation Project, West China Hospital, Sichuan University (22HXFH019(H.L)). Publisher Copyright: {\textcopyright} 2022, The Author(s).",

year = "2022",

month = dec,

doi = "10.1038/s41467-022-34395-2",

language = "English (US)",

volume = "13",

journal = "Nature Communications",

issn = "2041-1723",

publisher = "Nature Publishing Group",

number = "1",

}

TY - JOUR

T1 - Pan-cancer single-cell analysis reveals the heterogeneity and plasticity of cancer-associated fibroblasts in the tumor microenvironment

AU - Luo, Han

AU - Xia, Xuyang

AU - Huang, Li Bin

AU - An, Hyunsu

AU - Cao, Minyuan

AU - Kim, Gyeong Dae

AU - Chen, Hai Ning

AU - Zhang, Wei Han

AU - Shu, Yang

AU - Kong, Xiangyu

AU - Ren, Zhixiang

AU - Li, Pei Heng

AU - Liu, Yang

AU - Tang, Huairong

AU - Sun, Ronghao

AU - Li, Chao

AU - Bai, Bing

AU - Jia, Weiguo

AU - Liu, Yi

AU - Zhang, Wei

AU - Yang, Li

AU - Peng, Yong

AU - Dai, Lunzhi

AU - Hu, Hongbo

AU - Jiang, Yong

AU - Hu, Yiguo

AU - Zhu, Jingqiang

AU - Jiang, Hong

AU - Li, Zhihui

AU - Caulin, Carlos

AU - Park, Jihwan

AU - Xu, Heng

N1 - Funding Information: Appreciates the assistance of Mis. Xinyue Hu in illustration (Fig. ) design and drawing. This study was supported by the National Key R&D Program of China (No. 2021YFA1301203(H.X.), 2018YFC2000305(L.Z.D.)), National Natural Science Foundation of China (82103031(H.L.), 81973408(H.X.), 82272933 (H.L.), 82273445(Y.S.)), International Cooperation Project of Chengdu Municipal Science and Technology Bureau (2020-GH02-00017-HZ(H.L.)), 1.3.5 Project for Disciplines of Excellence, West China Hospital, Sichuan University (No. ZYYC20003(H.X.), ZYJC18035(H.L.), ZYJC18025(Z.H.L.), ZYJC18003(Y.L.), ZYJC18004(H.X.), and ZYYC20007(L.D.)), and the National Research Foundation of Korea funded by the Korean government (2019R1C1C1005403(J.P), 2019R1A4A1028802(J.P), 2021M3H9A2097520(J.P)), Clinical Research Incubation Project, West China Hospital, Sichuan University (22HXFH019(H.L)). Publisher Copyright: © 2022, The Author(s).

PY - 2022/12

Y1 - 2022/12

N2 - Cancer-associated fibroblasts (CAFs) are the predominant components of the tumor microenvironment (TME) and influence cancer hallmarks, but without systematic investigation on their ubiquitous characteristics across different cancer types. Here, we perform pan-cancer analysis on 226 samples across 10 solid cancer types to profile the TME at single-cell resolution, illustrating the commonalities/plasticity of heterogenous CAFs. Activation trajectory of the major CAF types is divided into three states, exhibiting distinct interactions with other cell components, and relating to prognosis of immunotherapy. Moreover, minor CAF components represent the alternative origin from other TME components (e.g., endothelia and macrophages). Particularly, the ubiquitous presentation of endothelial-to-mesenchymal transition CAF, which may interact with proximal SPP1+ tumor-associated macrophages, is implicated in endothelial-to-mesenchymal transition and survival stratifications. Our study comprehensively profiles the shared characteristics and dynamics of CAFs, and highlight their heterogeneity and plasticity across different cancer types. Browser of integrated pan-cancer single-cell information is available at https://gist-fgl.github.io/sc-caf-atlas/.

AB - Cancer-associated fibroblasts (CAFs) are the predominant components of the tumor microenvironment (TME) and influence cancer hallmarks, but without systematic investigation on their ubiquitous characteristics across different cancer types. Here, we perform pan-cancer analysis on 226 samples across 10 solid cancer types to profile the TME at single-cell resolution, illustrating the commonalities/plasticity of heterogenous CAFs. Activation trajectory of the major CAF types is divided into three states, exhibiting distinct interactions with other cell components, and relating to prognosis of immunotherapy. Moreover, minor CAF components represent the alternative origin from other TME components (e.g., endothelia and macrophages). Particularly, the ubiquitous presentation of endothelial-to-mesenchymal transition CAF, which may interact with proximal SPP1+ tumor-associated macrophages, is implicated in endothelial-to-mesenchymal transition and survival stratifications. Our study comprehensively profiles the shared characteristics and dynamics of CAFs, and highlight their heterogeneity and plasticity across different cancer types. Browser of integrated pan-cancer single-cell information is available at https://gist-fgl.github.io/sc-caf-atlas/.

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U2 - 10.1038/s41467-022-34395-2

DO - 10.1038/s41467-022-34395-2

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AN - SCOPUS:85141132770

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VL - 13

JO - Nature Communications

JF - Nature Communications

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M1 - 6619

ER -

Pan-cancer single-cell analysis reveals the heterogeneity and plasticity of cancer-associated fibroblasts in the tumor microenvironment

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