Single-cell sequencing of Klinefelter testicular biopsies
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ABSTRACT:
PROVIDER: PRJNA534098 | ENA |
REPOSITORIES: ENA
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Project description:We have evaluated the transcriptome of different testicular cell types, including germ cells, at single cell level in a testicular biopsy of a man with Klinefelter syndrome (XXY karyotype)
2019-08-30 | GSE130151 | GEO
Project description:Klinefelter syndrome (KS), also known as 47,XXY, is characterized by a distinct set of physiological abnormalities, commonly including infertility. The molecular basis for Klinefelter-related infertility is still unclear, largely due to the cellular complexity of the testis and the intricate endocrine and paracrine signaling that regulates spermatogenesis. Here, we demonstrate an analysis framework for dissecting human testis pathology that uses comparative analysis of single-cell RNA-sequencing data from the biopsies of 13 human donors. By comparing donors from a range of ages and forms of infertility, we generate gene expression signatures that characterize normal testicular function and distinguish clinically distinct forms of male infertility. Unexpectedly, we identified a subpopulation of Sertoli cells within multiple cases of KS that lack transcription from the XIST locus, with the consequence of increased X-linked gene expression compared to all other KS cell populations. By systematic assessment of known signaling pathways, we identify 72 pathways potentially active in testis, dozens of which appear upregulated in KS. Altogether our data support a model of pathogenic changes in interstitial cells cascading from loss of X-inactivation in pubertal Sertoli cells, and nominate testicular GNRH1 as a dosage-sensitive factor secreted by Sertoli cells that may contribute to the process. Our findings demonstrate the value of comparative patient analysis in mapping genetic mechanisms of disease, and identify an epigenetic phenomenon in KS Sertoli cells that may prove important for understanding causes of infertility and sex chromosome evolution.
2021-09-26 | GSE169062 | GEO
Project description:Objective: Klinefelter Syndrome (KS) is the most common sexual chromosome abnormality (47,XXY) and represents the first genetic cause of male infertility. The mechanisms leading to KS testis degeneration are still unclear and no therapy is so far available for affected patients. The present study is aimed to unravel information about molecules playing a key role in the disruption of the spermatogenesis. Design: Gene expression profiles analysis of KS azoospermic testis versus normal testis, could provide useful information about the molecular basis of the alteration of the spermatogenesis. Materials and Methods: Transcriptome analysis was performed carrying out gene expression profile by a whole genome microarray approach on testis biopsies obtained from 6 azoospermic non-mosaic KS men and from 3 controls, for a total of 12 experiments. T-test and False Discovery Rate were used to evaluate differentially expressed genes. Identified transcripts were analysed by Ingenuity Pathways Analysis software to disclose genes biological functions. Results: Data analysis revealed the differentially up- and down-expression, in KS testis versus the control ones, of 656 and 247 genes related to Endocrine system development and function, Lipid metabolism, Reproductive disease, Free radical scavenging, and Cell death. Conclusions: Take together these data show the presence of several genes involved in testis microenvironment deregulation leading to the spermatogenesis failure. This information, associated with an early diagnosis could help to unravel possible therapeutic targets for testis failure prevention and limitation. Gene expression profile of 6 azoospermic KS testicular biopsies versus 3 pooled control testicular biposies form patients with normal spermatogenesis. A total of 12 experiments was carried out including biological and technical replicates.
2014-06-15 | E-GEOD-54023 | biostudies-arrayexpress
Project description:The aim of the study was to identify in vivo spermatogonial gene expression within the context of their biological niche. Identification of spermatogonial genes was done by t-testing on the replicates of Score 3 (Spermatogonia) and Score 2 (SCO) testicular biopsies.
2009-11-13 | GSE18997 | GEO
Project description:The aim of the study was to identify in vivo spermatogonial gene expression within the context of their biological niche. Identification of spermatogonial genes was done by t-testing on the replicates of Score 3 (Spermatogonia) and Score 2 (SCO) testicular biopsies. 3 biological replicates with spermatogonial presence in the tubuli seminiferi, 5 biological replicates with Sertoli-cell-only syndrome.
2009-11-12 | E-GEOD-18997 | biostudies-arrayexpress
Project description:Testicular cancer is the most common solid malignancy in young men. Given the many histological classifications of testicular tumours, seminoma is one of the most treatable cancers. The survival rate in early-stage disease was more than 90%. Thus, seminoma at the cellular and molecular levels, especially at the single-cell level, is worth studying. We performed a single-cell RNA sequencing (scRNA-seq) study on a patient who was diagnosed with testicular seminoma with lymph node metastasis. This study presented tumour tissue, PBMC, pelvic and renal hilus lymph node in a total of 18,206 high-quality single-cell transcriptome information. The characteristics of metastatic cell lineage were revealed by the comparison between different tumour cell subtypes at the scRNA level. A single-cell map of testicular seminoma with lymph node metastasis was constructed by scRNA-seq. We discovered the gene expression characteristics of the tumour cells in testicular seminoma, especially metastatic tumour cells. KRT8 and KRT18 were commonly expressed in the three tumour cell subtypes. However, TCF7L1, SCG3 and SV2C were the specifically expressed genes of tumour cell subtypes in primary tumour sites. Some molecular markers specifically expressed by the metastatic cell lineage, such as POU5F1, were identified. We revealed the molecular characteristics of testicular seminoma at the single-cell level, especially the metastatic tumour cells. This study could provide new insights into the diagnosis and treatment of testicular seminoma.
2022-03-25 | GSE197778 | GEO
Project description:Transcriptomic differences between fibrotic and non-fibrotic testicular tissue reveal possible key players in Klinefelter syndrome-related testicular fibrosis
| PRJNA825978 | ENA
Project description:Postnatal human male gonad development and function are known to involve many genes and pathways but our understanding of genome-wide developmental stage-specific and cell type-specific gene expression is far from complete. Integration of testicular and somatic data could elucidate regulatory mechanisms specifically controlling spermatogenesis and may yield insight into certain reproductive pathologies. Please note: AdMinus means that there is no Ad spermatogonia in the corresponding testicular biopsies of cryptorchid children. AdPlus means that Ad spermatogonia are present in the corresponding testicular biopsies of cryptorchid children. JS refers to Johnsen score.
2012-10-28 | E-TABM-1214 | biostudies-arrayexpress
Project description:Single-cell sequencing reveals the relationship between phenotypes and genotypes of Klinefelter syndrome
| PRJNA562283 | ENA
Project description:One of the most common congenital disorders of male infertility is Klinefelter syndrome. Because of its extreme heterogeneity in clinical and genetic presentation, the relationship between transcriptome and the clinical phenotype and the associated co-morbidities seen in KS has not been fully clarified yet. We reported here a 47 XXY karyotype Chinese male (KS) with infertility and analyzed the differences in gene expression patterns of peripheral blood mononuclear cells (PBMCs) from a Chinese male and a female control with normal karyotype by single-cell sequencing. We analyzed a total of 24,439 cells and divided them into 5 immune cell types (including B cell, T cell, macrophage cell, dendritic cell, and natural killer cell) according to the marker genes. Using unsupervised dimensionality reduction and clustering algorithms, we identified molecularly distinct subpopulations of cells between KS and both controls. Gene ontology enrichment analyses yielded terms associated with well-known comorbidities seen in KS as well as an affected immune system, type I diabetes mellitus. Based on our data, we point towards several candidate genes, which may be implicated in the phenotype of KS. Overall, our analysis showed a comprehensive map of the cell types of the PBMCs of KS patient at the single-cell level, which will contribute to preventing comorbidity and improving the life quality of KS patients.
2019-08-27 | GSE136353 | GEO