Project description:Immature ovarian teratomas are malignant germ cell tumor composed of complicated cell types and are characterized by pathological features of immature neuroectodermal tubules/rosettes. To reveal the heterogeneity, evolution trajectory and cell communications among tumor microenvironment, we performed single-cell RNA sequencing (scRNA-seq) on three patient-derived immature ovarian teratomas (PDT) samples, and conducted systematically comparison with stem cell lines derived immature teratomas (CDT). 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. In conclusion, we provided the comprehensive profile of PDT at single cell level and highlighted the potential usage of CDTs as a model for research on PDT.
Project 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.
Project description:Ovarian immature teratoma (IM) is a type of germinal malignant tumor, affecting children, adolescents and young adults. Event-free survival is below 25% in high-grade IM. Pediatric IM is rare and seldom studied, raising controversial issues such as histopathological standard and lack of specific biomarkers. This study aimed to perform microRNA (miRNA) microarray and identify specific differentially expressed miRNAs in IMs than in other types of ovarian tumors. Our work enables practitioners to optimally exploit relevant characteristics for precise diagnostic and therapeutic strategies in IM.
Project description:Ovarian mature cystic teratomas (MCTs) originate from postmeiotic germ cells, and some are thought to result from the fusion of two ova. The aim of this study was to determine whether this mechanism is in fact involved in MCT development. MCTs can be classified by the zygosity of the centromere and distal chromosome regions. We evaluated the zygosity of all chromosomes from 38 MCT specimens using B allele frequency (BAF) plots of single nucleotide polymorphism-array data. Theoretically, MCTs originated from the fusion of two ova should have a mixed pattern of centromeric zygosity, i.e., a combination of heterozygous and homozygous regions. However, no MCTs in this series met this criterion as evidenced by BAF plots, suggesting that the fusion of two ova is not mechanistically involved in the development of ovarian teratomas. Thus, MCTs were classified into three types originating from meiosis I and meiosis II errors, and endoduplication of a mature ovum. The numbers of recombination events occurring with type I and II MCTs were somewhat higher than in regular oogenesis. In addition, BAF plots could facilitate the construction of recombination maps at the whole-genome level for type I and II MCTs. In conclusion, our findings provide evidence against the hypothesis that MCTs originate from the fusion of two ova and indicate that BAF plots could serve as useful analytical tools for analyzing MCT cytogenetics and human oocyte meiosis.
Project description:Canonical and non-canonical Wnt signaling play key roles during development and tumorigenesis. In this study we compared gene expression in teratomas grown from mouse embryonic stem cells that overexpress Evi/Wls and teratomas from normal embryonic stem cells cells.