Dedifferentiation of human adult Sertoli cells in cross talk with seminoma cells in vitro
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PROVIDER: PRJNA716997 | ENA |
REPOSITORIES: ENA
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Project description:Germ cell neoplasia in situ (GCNIS) is the noninvasive precursor of testicular germ cell tumors type II (TGCT), the most common cancer in young men. GCNIS originates from embryonic germ cells blocked in their maturation. The causes are unknown. GCNIS is associated with impaired Sertoli cells that express fetal marker keratin 18 (KRT18) and pluripotency factor SOX2. According to the spread theory of the origin of GCNIS, these impaired Sertoli cells are prepubertal cells arrested in their maturation due to genetic anomalies and/ or environmental anti-androgens. Thus, they are unable to support the development of germ cells, leading to their maturational block with further progression into GCNIS. The alternative theory states that the impaired Sertoli cells are adult cells dedifferentiating secondarily due to the influence of GCNIS. To address this issue, we established a co-culture model of adult human Sertoli cells (FS1) and a seminoma cell line similar to GCNIS (TCam-2). After 2 weeks of co-culture, FS1 cells showed progressive expression of KRT18 and SOX2. Interestingly, TCam-2 cells in co-culture showed SOX2 expression and upregulation of further pluripotency- and reprogramming-associated genes (LEFTY1/2, GAL, DPPA5, NODAL, ZIC3, DND1, DPPA3, GDF3, BCAT1, JARID2, and DNMT3B), suggesting a seminoma to embryonal carcinoma transition. Thus, our FS1/ TCam-2 co-culture model is a valuable tool to investigate interactions between Sertoli cells and tumor cells. Our studies of human testicular biopsies with GCNIS further suggest that the impaired Sertoli cells associated to GCNIS represent adult cells undergoing progressive dedifferentiation.
2022-03-01 | GSE169557 | GEO
Project description:Germ cell neoplasia in situ (GCNIS) is the noninvasive precursor of testicular germ cell tumors type II, the most common cancer in young men, which originates from embryonic germ cells blocked in their maturation. GCNIS is associated with impaired Sertoli cells (SCs) that express fetal keratin 18 (KRT18) and the pluripotency factor SRY-Box transcription factor 2 (SOX2). According to the current theory concerning the origin of GCNIS, these SCs are prepubertal cells arrested in their maturation due to (epi)genetic anomalies and/or environmental antiandrogens. Thus, they are unable to support the development of germ cells, which leads to their maturational block and further progresses into GCNIS. Alternatively, these SCs are hypothesized to be adult cells dedifferentiating secondarily under the influence of GCNIS. To examine whether tumor cells can dedifferentiate SCs, we established a coculture model of adult human SCs (FS1) and a seminoma cell line similar to GCNIS (TCam-2). After 2 wk of coculture, FS1 cells showed progressive expression of KRT18 and SOX2, mimicking the in vivo changes. TCam-2 cells showed SOX2 expression and upregulation of further pluripotency- and reprogramming-associated genes, suggesting a seminoma to embryonal carcinoma transition. Thus, our FS1/TCam-2 coculture model is a valuable tool for investigating interactions between SCs and seminoma cells. Our immunohistochemical and ultrastructural studies of human testicular biopsies with varying degrees of GCNIS compared to biopsies from fetuses, patients with androgen insensitivity syndrome, and patients showing normal spermatogenesis further suggest that GCNIS-associated SCs represent adult cells undergoing progressive dedifferentiation.
| S-EPMC8233172 | biostudies-literature
Project description:Elevated palmitic acid, a most abundant saturated fatty acid, is a risk factor for obesity complications. Here, we report that palmitic acid impairs spermatogenesis by inducing abnormal palmitoylation in Sertoli cells. Firstly, we proposed a correlation between palmitic acid and spermatogenesis by reporting a significant elevation of serum palmitic acid levels in patients with dyszoospermia. In palmitic acid -treated mice, the blood-testis barrier was found to be disrupted, and decreased tight junction protein expression was observed in palmitic acid-treated Sertoli cells. Palmitic acid entered the endoplasmic reticulum and induced endoplasmic reticulum stress, resulting in damage to Sertoli cell barriers.
2022-08-12 | PXD028778 | Pride
Project description:The sequential adipogenic differentiation and dedifferentiation processes resulted in novel stem cells that proliferated faster and retained multilineage potency; however, the mechanism underlying this cross-talk remained to be determined. In this context, we identified a number of differentially expressed genes during these processes. Gene expression profiling was performed to obtain a deeper molecular insight into AL cells and their subsequent dedifferentiation to primitive cell types with multilineage potency. GeneChips were generated for PDMSCs, AL cells and DePDMSCs from 3 donors. We selected numerous genes which were differentially expressed in the processes.
2015-10-14 | GSE73964 | GEO
Project description:Cancer associated fibroblasts (CAFs), mainly responsible for the desmoplastic reaction hallmark of intrahepatic Cholangiocarcinoma (iCCA), likely take a role in tumour aggressiveness and resistance to therapy, although the molecular mechanisms involved are unknown. Aim of the study is to investigate how targeting hCAF/iCCA cross-talk with a Notch1 inhibitor namely Crenigacestat would affect cancer progressionWe used different in vitro models in 2D and we established new 3D hetero-spheroids with iCCA cells and human (h)CAFs. Results were confirmed in a xenograft model, explanted tumoral tissues underwent transcriptomic and bioinformatic analysis. hCAFs/iCCA cross-talk sustains increased migration of both KKU-M213 and KKU-M156 cells, while Crenigacestat significantly inhibits only the cross-talk stimulated migration. Hetero-spheroids grow larger than homo-spheroids,formed by only iCCA cells. Crenigacestat significantly reduced invasion and growth of hetero- but not of homo-spheroids. In xenograft models, hCAFs/KKU-M213 tumours grew significantly larger than KKU-M213 tumours, but were significantly reduced in volume by Crenigacestat treatment, which also significantly reduced the fibrotic reaction. Interpretative phenomenological analysis of the transcriptome unveiled that genes of hCAFs/KKU-M213 but not of KKU-M213 tumours increased tumour lesions, and that Crenigacestat treatment inhibited the modulated canonical pathway. Cell cycle checkpoints were the most modulated pathway. In hetero-spheroids, the number of cells increased into G2/M cell cycle phase, while Crenigacestat significantly decreased the number into G2/M phase in hetero but not in homo-spheroids. The cross-talk hCAFs/iCCA is a new target for reducing cancer progression with drugs such as Crenigacestat.
2024-11-22 | GSE273905 | GEO
Project description:Gene expression patterns of testicular seminoma were analysed applying oligonucleotide microarrays in 40 specimens of different tumour stages (pT1, pT2, pT3) and in 3 normal testes. Keywords: ordered
2007-07-31 | GSE8607 | GEO
Project description:Purpose: The aim of the present study was to examine the biological differences between seminomas with occult and clinically apparent metastases at the time of diagnosis of the primary tumor to gain insight into the biology of these tumors and facilitate the identification of novel predictors of seminoma metastasis. Materials and Methods: Total RNA including small RNAs was isolated from testicular tumors of patients with pure seminoma presenting with lymphogenic metastasis (n=5, clinical stage IIb/c) and occult metastasis (n=5, clinical stage I). The regulation of biological processes was examined (1) throughout the mRNA transcriptome (whole genome microarrays, 8x60K Array, Agilent and 4 samples per group) and (2) the miRNA transcriptome employing small RNA next generation sequencing (SOLID, Life Technologies). Protein coding genes (mRNAs) and small RNAs showing a significant (> 2-fold) difference between the groups were identified. Finally (3), we examined 95 candidate miRNAs in 36 apparent metastasized and another 5 occult metastasized seminoma using logistic regression analysis. Results: Among 19,596 genes, on average 12,894 mRNAs appeared expressed (65.8%, SD +/- 2.4; range, 62.0–69.3%) and 16.99×106/13.94×106 small RNA reads were identified for apparent/occult metastasized seminoma. These reads on average convert into 9,901/9,675 small RNAs including 422/404 mature microRNAs. None of these mRNAs/small RNAs met our selection criteria for candidate genes. From 95 candidate miRNAs 44 appeared expressed, with 3 of them showing weak but significant (p=0.047-0.049) differences among both groups. Conclusions: Occult and apparent metastasized seminomas are biologically almost indistinguishable and probably represent no separate tumor entities. These findings may simplify future research on seminoma metastasis.
2014-02-21 | GSE55198 | GEO
Project description:To compare the the genomic profile of MEFs, immature Sertoli, mature Sertoli cells, and MEFs (NWD) after infection of Nr5a1, Wt1 and Dmrt1 after 1 month of dox exposure. MEFs (NWD) were infected with Nr5a1, Wt1 and Dmrt1 and were exposed to dox for 1 month. MEFs, immature Sertoli and mature Sertoli cells were cultured for 3 days and collected
2012-12-20 | E-GEOD-39649 | biostudies-arrayexpress
Project description:Sertoli cells provide nutrients and support for germ cell differentiation and maintain a stable microenvironment for spermatogenesis. Comprehensive identification of Sertoli cellular proteins is important in understanding spermatogenesis. In this study, we performed an integrative analysis of the proteome and phosphoproteome to explore the role of Sertoli cells in spermatogenesis. A total of 2912 and 753 proteins were identified from the proteome and phosphoproteome in Sertoli cells; 438 proteins were common to the proteome and phosphoproteome. In the proteome, ACTG1, ACTB, ACTA2, MYH9 were the most abundant proteins. Gene Ontology (GO) analysis indicated that most of the proteins are involved in the processes of localization, biosynthesis, gene expression, and transport. In addition, part of proteins related to Sertoli cell functions were also enriched. In the phosphoproteome, most of the proteins are involved in gene expression and the RNA metabolic process; the pathways mainly involve the spliceosome, mitogen-activated protein kinase（MAPK） signaling pathway, focal adhesion, and tight junctions. The pleckstrin homology-like domain is the most highly enriched protein domain in phosphoproteins. Cyclin-dependent kinases (CDKs) and protein kinases C (PKCs) were found to be highly active kinases in kinase-substrate network analysis. Ten proteins most closely related to network stability were found in the analysis of network interactions of proteins identified jointly by the phosphoproteome and proteome. Through immunohistochemistry and immunofluorescence verification of vimentin, it was found that there were localization differences between phosphorylated and non-phosphorylated vimentin in testicular tissue. This study is the first in-depth proteomic and phosphoproteomic analysis of the buffalo testicular Sertoli cells. The results provide insight into the role of Sertoli cells in spermatogenesis and provide clues for further study of male reproduction.
2021-05-07 | PXD024984 | Pride
Project description:To compare the the genomic profile of MEFs, immature Sertoli, mature Sertoli cells, and MEFs (NWD) after infection of Nr5a1, Wt1 and Dmrt1 after 1 month of dox exposure.
2012-12-20 | GSE39649 | GEO