In Vitro Propagation of XXY Human Klinefelter Spermatogonia Stem Cells; a step towards new fertility opportunities
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE208761 | GEO | 2022/10/18
REPOSITORIES: GEO
Similar Datasets
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) is characterized by a masculine phenotype, supernumerary sex chromosomes (usually XXY), and spermatogonial stem cell (SSC) loss in their early life. Affecting 1 out of every 650 males born, KS is the most common genetic cause of male infertility, and new fertility preservation strategies are critically important for these patients. In this study, testes from 41, XXY prepubertal (3-day-old) mice were frozen-thawed. Isolated testicular cells were cultured and characterized by qPCR, digital PCR, and flow cytometry analyses. We demonstrated that SSCs survived and were able to be propagated with testicular somatic cells in culture for up to 120 days. DNA fluorescent in situ hybridization (FISH) showed the presence of XXY spermatogonia at the beginning of the culture and a variety of propagated XY, XX, and XXY spermatogonia at the end of the culture. These data provide the first evidence that an extra sex chromosome was lost during innate SSC culture, a crucial finding in treating KS patients for preserving and propagating SSCs for future sperm production, either in vitro or in vivo. This in vitro propagation system can be translated to clinical fertility preservation for KS patients.
| S-EPMC8745151 | biostudies-literature
Project description:Klinefelter syndrome (KS) is the most prevalent aneuploidy in males and is characterized by an extra copy of the X chromosome,while the non-mosaic form of KS with 47,XXY karyotype is the most frequent (80-90%), less common non-disjunction events during the early mitotic division of the zygote result in mosaic forms of KS (47,XXY/46,XY). Here, using a paradigmatic cohort of KS-inducible pluripotent stem cells (iPSCs) carrying 47,XXY karyotypes we present the first iPSC-based disease-modeling study performed on KS patients from Saudi Arabia. We profiled the transcriptome of these Saudi KS-iPSCs, virtually characterized by subduedcgenetic backgrounds. Moreover, we performed a comparative transcriptomic analysis to assess the aberrant gene expression profile due to X dosage imbalance in four Saudi and five European and North American 47,XXY patients-derived iPSCs from our previously published study on KS and high-grade sex chromosome aneuploidies (SCAs). We identified a transcriptomic signature including ten PAR1 genes and thirteen non-PAR escape genes consistently upregulated in KS compared to 46,XY controls in both groups, as well as 193 consistenty disregulated autosomal genes. Our results indicate that the global transcriptional impact of X chromosome overdosage in KS is largely attributable to X-linked genes escaping X inactivation, regardless of the geographical area of origin, ethnicity, and genetic background.
2023-08-02 | GSE220268 | GEO
Project description:Analysis of gene expression in the striatum in a mouse model of Klinefelter Syndrome (the Sex Chromosome Trisomy model). The hypothesis tested was that feminization of partner preference was also reflected on a molecular level 4 different genotypes were analyzed (XX female, XY male, XXY male, XX male). There were 8-12 biological replicates per genotype for a total of 38 samples.
2013-07-12 | E-GEOD-48784 | biostudies-arrayexpress
Project description:Please see publication. These experiments were performed to ascertain the contribution of Y-linked rDNA copy number variation in the modulation of gene expression. Males (XY) and female (XXY) genotypes were probed.
2011-08-01 | GSE27695 | GEO
Project description:We developed a cellular model to study sex differences in humans. Using somatic cells from a mosaic Kleinefelter patient, we generated isogenic human induced pluripotent stem cell lines with different sex chromosome complements – 47,XXY / 46,XX / 46,XY and 45,X0. 46, XX and 46, XY hiPSCs were differentiated to neural progenitor cells and compared.
2022-11-24 | GSE145118 | 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:Klinefelter syndrome (KS) is the most common male chromosomal abnormality (47,XXY). Males with KS suffers from numerous comorbidities. Gene expression data integrated with other data types can increase the knowledge and clinically handling of KS males. Gene expression microarray from eight human Klinefelter syndrome patients (47,XXY) and eight human controls. The age of the Klinefelter syndrome patients varied, which was corrected for in the pre-processing as described in the paper and also in the 'normalization data transformation protocol' of this submission.
2017-03-23 | E-MTAB-4922 | biostudies-arrayexpress
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:Please see publication. These experiments were performed to ascertain the contribution of Y-linked rDNA copy number variation in the modulation of gene expression. Males (XY) and female (XXY) genotypes were probed. Dye swaps and direct comparisons within each sex
2011-07-31 | E-GEOD-27695 | biostudies-arrayexpress