Characterization of immature ovarian teratomas through single-cell transcriptome
IntroductionImmature 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)...
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Frontiers Media S.A.
2023-03-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2023.1131814/full |
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| author | Minyuan Cao Yun Deng Yiqi Deng Jing Wu Chongyi Yang Zijun Wang Qianqian Hou Huancheng Fu Zhixiang Ren Xuyang Xia Yue Li Wei Wang Heng Xu Heng Xu Xin Liao Yang Shu Yang Shu |
| author_facet | Minyuan Cao Yun Deng Yiqi Deng Jing Wu Chongyi Yang Zijun Wang Qianqian Hou Huancheng Fu Zhixiang Ren Xuyang Xia Yue Li Wei Wang Heng Xu Heng Xu Xin Liao Yang Shu Yang Shu |
| author_sort | Minyuan Cao |
| collection | DOAJ |
| description | IntroductionImmature 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.MethodsSingle-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.ResultA 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.DiscussionThis 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. |
| first_indexed | 2024-04-10T06:04:23Z |
| format | Article |
| id | doaj.art-e1d7b11bf6024503922da10277da8528 |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-04-10T06:04:23Z |
| publishDate | 2023-03-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-e1d7b11bf6024503922da10277da85282023-03-03T05:05:16ZengFrontiers Media S.A.Frontiers in Immunology1664-32242023-03-011410.3389/fimmu.2023.11318141131814Characterization of immature ovarian teratomas through single-cell transcriptomeMinyuan Cao0Yun Deng1Yiqi Deng2Jing Wu3Chongyi Yang4Zijun Wang5Qianqian Hou6Huancheng Fu7Zhixiang Ren8Xuyang Xia9Yue Li10Wei Wang11Heng Xu12Heng Xu13Xin Liao14Yang Shu15Yang Shu16State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, Chengdu, Sichuan, ChinaState Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, Chengdu, Sichuan, ChinaState Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, Chengdu, Sichuan, ChinaState Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, Chengdu, Sichuan, ChinaCollege of Life Sciences, Sichuan University, Chengdu, Sichuan, ChinaCollege of Life Sciences, Sichuan University, Chengdu, Sichuan, ChinaState Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, Chengdu, Sichuan, ChinaState Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, Chengdu, Sichuan, ChinaState Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, Chengdu, Sichuan, ChinaState Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, Chengdu, Sichuan, ChinaResearch Core Facility of West China Hospital, Sichuan University, Chengdu, Sichuan, ChinaDepartment of Pathology, West China Second Hospital, Sichuan University, Chengdu, Sichuan, ChinaState Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, Chengdu, Sichuan, ChinaDivision of Laboratory Medicine, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, Sichuan, ChinaDepartment of Pathology, West China Second Hospital, Sichuan University, Chengdu, Sichuan, ChinaState Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, Chengdu, Sichuan, ChinaGastric Cancer Center, West China Hospital, Sichuan University, Chengdu, Sichuan, ChinaIntroductionImmature 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.MethodsSingle-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.ResultA 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.DiscussionThis 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.https://www.frontiersin.org/articles/10.3389/fimmu.2023.1131814/fullimmature teratomasingle cell RNA sequencingpluripotent stem cellimmature neuronradial gliatumor immune microenvironment |
| spellingShingle | Minyuan Cao Yun Deng Yiqi Deng Jing Wu Chongyi Yang Zijun Wang Qianqian Hou Huancheng Fu Zhixiang Ren Xuyang Xia Yue Li Wei Wang Heng Xu Heng Xu Xin Liao Yang Shu Yang Shu Characterization of immature ovarian teratomas through single-cell transcriptome Frontiers in Immunology immature teratoma single cell RNA sequencing pluripotent stem cell immature neuron radial glia tumor immune microenvironment |
| 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 | immature teratoma single cell RNA sequencing pluripotent stem cell immature neuron radial glia tumor immune microenvironment |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2023.1131814/full |
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