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Characterization of immature ovarian teratomas through single-cell transcriptome

INTRODUCTION: Immature ovarian teratomas are a type of malignant germ cell tumor composed of complicated cell types and are characterized by pathological features of immature neuroectodermal tubules/rosettes. However, there is a lack of understanding of patient-derived immature ovarian teratomas (PD...

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Autores principales: Cao, Minyuan, Deng, Yun, Deng, Yiqi, Wu, Jing, Yang, Chongyi, Wang, Zijun, Hou, Qianqian, Fu, Huancheng, Ren, Zhixiang, Xia, Xuyang, Li, Yue, Wang, Wei, Xu, Heng, Liao, Xin, Shu, Yang
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10020330/
https://www.ncbi.nlm.nih.gov/pubmed/36936909
http://dx.doi.org/10.3389/fimmu.2023.1131814
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author Cao, Minyuan
Deng, Yun
Deng, Yiqi
Wu, Jing
Yang, Chongyi
Wang, Zijun
Hou, Qianqian
Fu, Huancheng
Ren, Zhixiang
Xia, Xuyang
Li, Yue
Wang, Wei
Xu, Heng
Liao, Xin
Shu, Yang
author_facet Cao, Minyuan
Deng, Yun
Deng, Yiqi
Wu, Jing
Yang, Chongyi
Wang, Zijun
Hou, Qianqian
Fu, Huancheng
Ren, Zhixiang
Xia, Xuyang
Li, Yue
Wang, Wei
Xu, Heng
Liao, Xin
Shu, Yang
author_sort Cao, Minyuan
collection PubMed
description INTRODUCTION: Immature ovarian teratomas are a type of malignant germ cell tumor composed of complicated cell types and are characterized by pathological features of immature neuroectodermal tubules/rosettes. However, there is a lack of understanding of patient-derived immature ovarian teratomas (PDT) at the single cell level. Moreover, whether stem cell lines derived from immature teratomas (CDT) can be used as models for research on PDT remains to be elucidated. METHODS: Single-cell RNA sequencing (scRNA-seq) and subsequent bioinformatic analysis was performed on three patient-derived immature ovarian teratomas (PDT) samples to reveal the heterogeneity, evolution trajectory, and cell communication within the tumor microenvironment of PDT. Validations were conducted in additional seven samples through multiplex immunofluorescence. RESULT: A total of qualified 22,153 cells were obtained and divided into 28 clusters, which can match to the scRNA-seq annotation of CDT as well as human fetal Cell Atlas, but with higher heterogeneity and more prolific cell-cell crosstalk. Radial glia cells (tagged by SOX2) and immature neuron (tagged by DCX) exhibited mutually exclusive expression and differentiated along distinct evolutionary trajectory from cycling neural progenitors. Proportions of these neuroectodermal cell subtypes may play important roles in PDT through contributing to the internal heterogeneity of PDTs. Moreover, the immune cells in PDTs were infiltrated rather than teratoma-derived, with more abundant macrophage in immature neuron than those in radial glia cells, and the infiltrated macrophage subtypes (i.e., M1 and M2) were significantly correlated to clinical grade. Overall, suppressed evolution process and transcriptome regulation in neuroectodermal cells, reduced cell-cell crosstalk, higher M1/M2 proportion ratio, and enhanced T cell effects in tumor microenvironment are enriched in patients with favorable prognosis. DISCUSSION: This study provides a comprehensive profile of PDT at the single cell level, shedding light on the heterogeneity and evolution of neuroectodermal cells within PDTs and the role of immune cells within the tumor microenvironment. Also, our findings highlight the potential usage of CDTs as a model for research on PDT.
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spelling pubmed-100203302023-03-18 Characterization of immature ovarian teratomas through single-cell transcriptome Cao, Minyuan Deng, Yun Deng, Yiqi Wu, Jing Yang, Chongyi Wang, Zijun Hou, Qianqian Fu, Huancheng Ren, Zhixiang Xia, Xuyang Li, Yue Wang, Wei Xu, Heng Liao, Xin Shu, Yang Front Immunol Immunology INTRODUCTION: Immature ovarian teratomas are a type of malignant germ cell tumor composed of complicated cell types and are characterized by pathological features of immature neuroectodermal tubules/rosettes. However, there is a lack of understanding of patient-derived immature ovarian teratomas (PDT) at the single cell level. Moreover, whether stem cell lines derived from immature teratomas (CDT) can be used as models for research on PDT remains to be elucidated. METHODS: Single-cell RNA sequencing (scRNA-seq) and subsequent bioinformatic analysis was performed on three patient-derived immature ovarian teratomas (PDT) samples to reveal the heterogeneity, evolution trajectory, and cell communication within the tumor microenvironment of PDT. Validations were conducted in additional seven samples through multiplex immunofluorescence. RESULT: A total of qualified 22,153 cells were obtained and divided into 28 clusters, which can match to the scRNA-seq annotation of CDT as well as human fetal Cell Atlas, but with higher heterogeneity and more prolific cell-cell crosstalk. Radial glia cells (tagged by SOX2) and immature neuron (tagged by DCX) exhibited mutually exclusive expression and differentiated along distinct evolutionary trajectory from cycling neural progenitors. Proportions of these neuroectodermal cell subtypes may play important roles in PDT through contributing to the internal heterogeneity of PDTs. Moreover, the immune cells in PDTs were infiltrated rather than teratoma-derived, with more abundant macrophage in immature neuron than those in radial glia cells, and the infiltrated macrophage subtypes (i.e., M1 and M2) were significantly correlated to clinical grade. Overall, suppressed evolution process and transcriptome regulation in neuroectodermal cells, reduced cell-cell crosstalk, higher M1/M2 proportion ratio, and enhanced T cell effects in tumor microenvironment are enriched in patients with favorable prognosis. DISCUSSION: This study provides a comprehensive profile of PDT at the single cell level, shedding light on the heterogeneity and evolution of neuroectodermal cells within PDTs and the role of immune cells within the tumor microenvironment. Also, our findings highlight the potential usage of CDTs as a model for research on PDT. Frontiers Media S.A. 2023-03-03 /pmc/articles/PMC10020330/ /pubmed/36936909 http://dx.doi.org/10.3389/fimmu.2023.1131814 Text en Copyright © 2023 Cao, Deng, Deng, Wu, Yang, Wang, Hou, Fu, Ren, Xia, Li, Wang, Xu, Liao and Shu https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Immunology
Cao, Minyuan
Deng, Yun
Deng, Yiqi
Wu, Jing
Yang, Chongyi
Wang, Zijun
Hou, Qianqian
Fu, Huancheng
Ren, Zhixiang
Xia, Xuyang
Li, Yue
Wang, Wei
Xu, Heng
Liao, Xin
Shu, Yang
Characterization of immature ovarian teratomas through single-cell transcriptome
title Characterization of immature ovarian teratomas through single-cell transcriptome
title_full Characterization of immature ovarian teratomas through single-cell transcriptome
title_fullStr Characterization of immature ovarian teratomas through single-cell transcriptome
title_full_unstemmed Characterization of immature ovarian teratomas through single-cell transcriptome
title_short Characterization of immature ovarian teratomas through single-cell transcriptome
title_sort characterization of immature ovarian teratomas through single-cell transcriptome
topic Immunology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10020330/
https://www.ncbi.nlm.nih.gov/pubmed/36936909
http://dx.doi.org/10.3389/fimmu.2023.1131814
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