Integrated single-cell transcriptome analysis reveals heterogeneity of esophageal squamous cell carcinoma microenvironment

Huy Q. Dinh; Feng Pan; Geng Wang; Qing Feng Huang; Claire E. Olingy; Zhi Yong Wu; Shao Hong Wang; Xin Xu; Xiu E. Xu; Jian Zhong He; Qian Yang; Sandra Orsulic; Marcela Haro; Li Yan Li; Guo Wei Huang; Joshua J. Breunig; H. Phillip Koeffler; Catherine C. Hedrick; Li Yan Xu; De Chen Lin; En Min Li

doi:10.1038/s41467-021-27599-5

Integrated single-cell transcriptome analysis reveals heterogeneity of esophageal squamous cell carcinoma microenvironment

Huy Q. Dinh, Feng Pan, Geng Wang, Qing Feng Huang, Claire E. Olingy, Zhi Yong Wu, Shao Hong Wang, Xin Xu, Xiu E. Xu, Jian Zhong He, Qian Yang, Sandra Orsulic, Marcela Haro, Li Yan Li, Guo Wei Huang, Joshua J. Breunig, H. Phillip Koeffler, Catherine C. Hedrick, Li Yan Xu, De Chen LinEn Min Li

Research output: Contribution to journal › Article › peer-review

61 Scopus citations

Abstract

The tumor microenvironment is a highly complex ecosystem of diverse cell types, which shape cancer biology and impact the responsiveness to therapy. Here, we analyze the microenvironment of esophageal squamous cell carcinoma (ESCC) using single-cell transcriptome sequencing in 62,161 cells from blood, adjacent nonmalignant and matched tumor samples from 11 ESCC patients. We uncover heterogeneity in most cell types of the ESCC stroma, particularly in the fibroblast and immune cell compartments. We identify a tumor-specific subset of CST1⁺ myofibroblasts with prognostic values and potential biological significance. CST1⁺ myofibroblasts are also highly tumor-specific in other cancer types. Additionally, a subset of antigen-presenting fibroblasts is revealed and validated. Analyses of myeloid and T lymphoid lineages highlight the immunosuppressive nature of the ESCC microenvironment, and identify cancer-specific expression of immune checkpoint inhibitors. This work establishes a rich resource of stromal cell types of the ESCC microenvironment for further understanding of ESCC biology.

Original language	English (US)
Article number	7335
Journal	Nature communications
Volume	12
Issue number	1
DOIs	https://doi.org/10.1038/s41467-021-27599-5
State	Published - Dec 2021
Externally published	Yes

ASJC Scopus subject areas

General Chemistry
General Biochemistry, Genetics and Molecular Biology
General Physics and Astronomy

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1038/s41467-021-27599-5

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Dinh, H. Q., Pan, F., Wang, G., Huang, Q. F., Olingy, C. E., Wu, Z. Y., Wang, S. H., Xu, X., Xu, X. E., He, J. Z., Yang, Q., Orsulic, S., Haro, M., Li, L. Y., Huang, G. W., Breunig, J. J., Koeffler, H. P., Hedrick, C. C., Xu, L. Y., ... Li, E. M. (2021). Integrated single-cell transcriptome analysis reveals heterogeneity of esophageal squamous cell carcinoma microenvironment. Nature communications, 12(1), Article 7335. https://doi.org/10.1038/s41467-021-27599-5

Dinh, HQ, Pan, F, Wang, G, Huang, QF, Olingy, CE, Wu, ZY, Wang, SH, Xu, X, Xu, XE, He, JZ, Yang, Q, Orsulic, S, Haro, M, Li, LY, Huang, GW, Breunig, JJ, Koeffler, HP, Hedrick, CC, Xu, LY, Lin, DC & Li, EM 2021, 'Integrated single-cell transcriptome analysis reveals heterogeneity of esophageal squamous cell carcinoma microenvironment', Nature communications, vol. 12, no. 1, 7335. https://doi.org/10.1038/s41467-021-27599-5

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title = "Integrated single-cell transcriptome analysis reveals heterogeneity of esophageal squamous cell carcinoma microenvironment",

abstract = "The tumor microenvironment is a highly complex ecosystem of diverse cell types, which shape cancer biology and impact the responsiveness to therapy. Here, we analyze the microenvironment of esophageal squamous cell carcinoma (ESCC) using single-cell transcriptome sequencing in 62,161 cells from blood, adjacent nonmalignant and matched tumor samples from 11 ESCC patients. We uncover heterogeneity in most cell types of the ESCC stroma, particularly in the fibroblast and immune cell compartments. We identify a tumor-specific subset of CST1+ myofibroblasts with prognostic values and potential biological significance. CST1+ myofibroblasts are also highly tumor-specific in other cancer types. Additionally, a subset of antigen-presenting fibroblasts is revealed and validated. Analyses of myeloid and T lymphoid lineages highlight the immunosuppressive nature of the ESCC microenvironment, and identify cancer-specific expression of immune checkpoint inhibitors. This work establishes a rich resource of stromal cell types of the ESCC microenvironment for further understanding of ESCC biology.",

author = "Dinh, {Huy Q.} and Feng Pan and Geng Wang and Huang, {Qing Feng} and Olingy, {Claire E.} and Wu, {Zhi Yong} and Wang, {Shao Hong} and Xin Xu and Xu, {Xiu E.} and He, {Jian Zhong} and Qian Yang and Sandra Orsulic and Marcela Haro and Li, {Li Yan} and Huang, {Guo Wei} and Breunig, {Joshua J.} and Koeffler, {H. Phillip} and Hedrick, {Catherine C.} and Xu, {Li Yan} and Lin, {De Chen} and Li, {En Min}",

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year = "2021",

month = dec,

doi = "10.1038/s41467-021-27599-5",

language = "English (US)",

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T1 - Integrated single-cell transcriptome analysis reveals heterogeneity of esophageal squamous cell carcinoma microenvironment

AU - Dinh, Huy Q.

AU - Pan, Feng

AU - Wang, Geng

AU - Huang, Qing Feng

AU - Olingy, Claire E.

AU - Wu, Zhi Yong

AU - Wang, Shao Hong

AU - Xu, Xin

AU - Xu, Xiu E.

AU - He, Jian Zhong

AU - Yang, Qian

AU - Orsulic, Sandra

AU - Haro, Marcela

AU - Li, Li Yan

AU - Huang, Guo Wei

AU - Breunig, Joshua J.

AU - Koeffler, H. Phillip

AU - Hedrick, Catherine C.

AU - Xu, Li Yan

AU - Lin, De Chen

AU - Li, En Min

PY - 2021/12

Y1 - 2021/12

N2 - The tumor microenvironment is a highly complex ecosystem of diverse cell types, which shape cancer biology and impact the responsiveness to therapy. Here, we analyze the microenvironment of esophageal squamous cell carcinoma (ESCC) using single-cell transcriptome sequencing in 62,161 cells from blood, adjacent nonmalignant and matched tumor samples from 11 ESCC patients. We uncover heterogeneity in most cell types of the ESCC stroma, particularly in the fibroblast and immune cell compartments. We identify a tumor-specific subset of CST1+ myofibroblasts with prognostic values and potential biological significance. CST1+ myofibroblasts are also highly tumor-specific in other cancer types. Additionally, a subset of antigen-presenting fibroblasts is revealed and validated. Analyses of myeloid and T lymphoid lineages highlight the immunosuppressive nature of the ESCC microenvironment, and identify cancer-specific expression of immune checkpoint inhibitors. This work establishes a rich resource of stromal cell types of the ESCC microenvironment for further understanding of ESCC biology.

AB - The tumor microenvironment is a highly complex ecosystem of diverse cell types, which shape cancer biology and impact the responsiveness to therapy. Here, we analyze the microenvironment of esophageal squamous cell carcinoma (ESCC) using single-cell transcriptome sequencing in 62,161 cells from blood, adjacent nonmalignant and matched tumor samples from 11 ESCC patients. We uncover heterogeneity in most cell types of the ESCC stroma, particularly in the fibroblast and immune cell compartments. We identify a tumor-specific subset of CST1+ myofibroblasts with prognostic values and potential biological significance. CST1+ myofibroblasts are also highly tumor-specific in other cancer types. Additionally, a subset of antigen-presenting fibroblasts is revealed and validated. Analyses of myeloid and T lymphoid lineages highlight the immunosuppressive nature of the ESCC microenvironment, and identify cancer-specific expression of immune checkpoint inhibitors. This work establishes a rich resource of stromal cell types of the ESCC microenvironment for further understanding of ESCC biology.

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Integrated single-cell transcriptome analysis reveals heterogeneity of esophageal squamous cell carcinoma microenvironment

Abstract

ASJC Scopus subject areas

UN SDGs

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