Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Genome-wide maps of PA1-bound sites in mice Sertoli cells

ABSTRACT: Blood-testis barrier (BTB) is essential to the microenvironment of spermatogenesis, and Sertoli cells provide the cellular basis for BTB construction. Numerous nuclear transcription factors have been identified to be vital for the proper functions of Sertoli cells. PA1 has been reported to play important roles during diverse biological processes, while its potential function in male reproduction is still unknown. Here, we show that PA1 was highly expressed in human and mouse testis and predominantly localized in the nuclei of Sertoli cells. Sertoli cell-specific Pa1 knockout resulted in azoospermia-like phenotype in mice. The knockout of this gene lead to multiple defects in spermatogenesis, such as the disorganization of cytoskeleton at basal and apical ectoplasmic specialization and the disruption of the BTB. Further transcriptomic analysis together with Cut-Tag results of PA1 in Sertoli cells revealed that PA1 could affect the expression of a subset of genes which are essential for the normal functions of Sertoli cells including those genes associated with actin organization and cellular junction such as Connexin43 (Cx43). We further demonstrated that the expression of Cx43 depended on the interaction between JUN, one of the AP-1 complex transcription factors, and PA1. Overall, our findings firstly revealed that PA1 is essential to the maintaining of BTB integrity in Sertoli cells, it regulates BTB construction-related gene expression via interacting a transcription factor, thus providing a potential diagnostic or even therapeutic target for some azoospermia patients.

ORGANISM(S): Mus musculus

PROVIDER: GSE188307 | GEO | 2022/04/13

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Similar Datasets

The transcriptome of Pa1-/- and Pa1F/F Sertoli cells purified from 20d-old mice testes

Project description:The blood-testis barrier (BTB) is essential to the microenvironment of spermatogenesis, and Sertoli cells provide the cellular basis for BTB construction. Numerous nuclear transcription factors have been identified to be vital for the proper functioning of Sertoli cells. PA1 has been reported to play important roles during diverse biological processes, yet its potential function in male reproduction is still unknown. Here, we show that PA1 was highly expressed in human and mouse testis and predominantly localized in the nuclei of Sertoli cells. Sertoli cell-specific Pa1 knockout resulted in an azoospermia-like phenotype in mice. The knockout of this gene led to multiple defects in spermatogenesis, such as the disorganization of the cytoskeleton during basal and apical ectoplasmic specialization and the disruption of the BTB. Further transcriptomic analysis, together with Cut-Tag results of PA1 in Sertoli cells, revealed that PA1 could affect the expression of a subset of genes that are essential for the normal function of Sertoli cells, including those genes associated with actin organization and cellular junctions such as Connexin43 (Cx43). We further demonstrated that the expression of Cx43 depended on the interaction between JUN, one of the AP-1 complex transcription factors, and PA1. Overall, our findings reveal that PA1 is essential for the maintenance of BTB integrity in Sertoli cells and regulates BTB construction-related gene expression via transcription factors. Thus, this newly discovered mechanism in Sertoli cells provides a potential diagnostic or even therapeutic target for some individuals with azoospermia.

2022-04-13 | GSE188308 | GEO

Induction of Sertoli-like cells from human fibroblasts by NR5A1 and GATA4

Project description:Sertoli cells are essential nurse cells in the testis that regulate the process of spermatogenesis and establish the immune-privileged environment of the blood-testis-barrier (BTB). The induction of human Sertoli cells from fibroblasts could provide cellular sources for fertility and transplantation treatments. Here, we report the in vitro reprogramming of human fibroblasts to Sertoli cells and characterize these human induced Sertoli-like cells (hiSCs). Initially, five transcriptional factors (NR5A1, GATA4, WT1, SOX9 and DMRT1) and a gene reporter carrying the AMH promoter were utilized to obtain the hiSCs. We further reduce the number of reprogramming factors to two, i.e., NR5A1 and GATA4, and show that these hiSCs have transcriptome profiles that are similar to those of primary human Sertoli cells. Consistent with the known cellular properties of Sertoli cells, hiSCs attract endothelial cells and exhibit high number of lipid droplets in the cytoplasm. More importantly, hiSCs can sustain the viability of spermatogonia cells harvested from mouse seminiferous tubules. In addition, hiSCs suppress the production of IL-2 and proliferation of human T lymphocytes. When hiSCs were cotransplanted with human embryonic kidney cells, these xenotransplanted human cells survived longer in mice with normal immune systems. hiSCs also allow us to determine a gene associated with Sertoli-only syndrome (SCO), CX43, is indeed important in regulating the maturation of Sertoli cells.

2019-11-26 | GSE133757 | GEO

Targeting APLN/APJ restores blood-testis barrier and improves spermatogenesis in murine and human diabetic models

Project description:Type 2 diabetes mellitus is one of the most prevalent metabolic diseases affecting multiple organs, including reproductive disorders in male diabetic patients. However, the molecular mechanisms that contribute to spermatogenesis dysfunction in diabetic patients have not yet been fully elucidated. Here, we performed Smart-seq2 to examine the transcriptome of diabetic patients' testis cells at single cell resolution including all major cell types of the testis. Intriguingly, whereas spermatogenesis appears largely preserved, the gene expression profiles of Sertoli cells and the blood-testis barrier (BTB) structure were dramatically impaired. Among the deregulated pathways, the Apelin (APLN) peptide /Apelin-receptor (APJ) axis was hyper-activated in diabetic patients. Mechanistically, APLN is produced locally by Sertoli cells upon high glucose treatment, which subsequently suppressed the production of carnitine and repressed the expression of cell adhesion genes in Sertoli cells. Together, these effects culminated in BTB structural dysfunction. Finally, using the small molecule APLN receptor antagonist, ML221, we show that blocking APLN/APJ significantly ameliorated the BTB damage and, importantly, improved functional spermatogenesis in diabetic db/db mice. We also translated and validated these findings in cultured human testis. Our findings identify the APLN/APJ axis as a promising therapeutic target to improve reproduction capacity in male diabetic patients.

2022-10-27 | GSE179080 | GEO

Newt (Cynops pyrrhogaster) testis proteomics during FSH/PRL stimulations

Project description:Newt testis is an appropriate model to isolate germ cells at a specific stage and study the effect of various factors on specific stage of spermatogenesis. Spermatogenesis is an essential process for sexual reproduction in development. It is triggered by the sequential mitotic divisions of spermatogonia, followed by their differentiation into spermatocytes. After two meiotic divisions, spermatocytes develop into spermatids, which possess half the normal complement of genetic material, and then into spermatozoa, mature male gametes in many sexually reproducing organisms. This complex process is controlled by cooperation with several hormones and testicular somatic cells, such as Follicle-stimulating hormone (FSH) and Prolactin (PRL). They are secreted by the pituitary gland and act on testicular somatic cells, mainly Sertoli cells, through the specific receptor. Sertoli cells have essential roles in the regulation of spermatogenesis. They not only represent the only cellular component of the blood–testis barrier but also produce and secrete local factors to germ cells. In this study, Primary Sertoli cells were established from Newt testis, and analyzed their proteome changes during the stimulation of FSH/PRL by 2D-DIGE (IC-Dyes).

2019-12-01 | PXD008342 | JPOST Repository

Transcriptome comparison of active, inactivating and regressed testes of Talpa occidentalis

Project description:We study the changes occurring in the testes of Talpa occidentalis during the breeding cycle. The transcriptomic analysis of active, inactivating and regressed testis show that several molecular pathways that operate in Sertoli cells, involved in the control of spermatogenesis and BTB dynamics, are deregulated in the inactive gonad, and that the immuno privilege of the testes is lost during the non-breeding season.

2021-12-31 | E-MTAB-10836 | biostudies-arrayexpress

Transcriptome comparison of active and regressed testes of Microtus duodecimcostatus

Project description:We also study the changes occurring in the testes of Mediterranean pine mice living in the wastelands during the breeding cycle. The transcriptomic analysis of active and regressed testis show that several molecular pathways that operate in Sertoli cells, involved in the control of spermatogenesis and BTB dynamics, are deregulated in the inactive gonad, and that the immuno privilege of the testes is lost during the non-breeding season.

2021-08-02 | E-MTAB-10291 | biostudies-arrayexpress

RNF20 is required for male fertility through H2B ubiquitination in Sertoli cells

Project description:Spermatogenesis is an essential process to generate male gametes in vertebrates, and it has become an important social health problem caused by spermatogenesis disorder. However, the molecular mechanism underlying spermatogenesis, particularly epigenetic modification in Sertoli cells of testis, remain elusive. In this study we generated Rnf20 conditional knockout mice by recombinant mothed, and only to find that Rnf20 knockout in Sertoli cells led to male infertility.

2023-04-12 | GSE225232 | GEO

Expression data from Shp2f/f and SCSKO mice testis

Project description:The ability of male reproduction is seriously dependent on Sertoli cells. However, the mechanisms governing the functional integrity of Sertoli cells remained largely unexplored. Tyrosine phosphatase protein Shp2 is expressed in germ, Leydig and Sertoli cells of mice testes. But the physiological role of Shp2 in the spermatogenesis was not fully understood. Thus, we conditionally deleted Shp2 gene in Sertoli cells using two transgenic models, and demonstrated that Shp2 deficiency caused infertility, excessive differentiation of SSCs and abnormal BTB in mice. To further discover the underlying mechanism of Shp2 regulation, we collected the mRNA of testes from wild type or knockout mice at 16.5 fetal day, Postnatal 3 days, 1 weeks, 2 weeks, and then screened the gene expression. Testis tissues from Shp2f/f and SCSKO mice were for RNA extraction and hybridization on Affymetrix microarrays.

2015-05-14 | E-GEOD-68829 | biostudies-arrayexpress

Epigenetic Transgenerational Inheritance of Testis Pathology and Sertoli Cell Epimutations: Generational Origins of Male Infertility

Project description:Environmental toxicant induced epigenetic transgenerational inheritance has been shown to affect testis pathology and sperm count. Sertoli cells have an essential role in spermatogenesis by providing physical and nutritional support for developing germ cells. The current study was designed to further investigate the transgenerational epigenetic changes in the rat Sertoli cell epigenome that are associated with the onset of testis disease.

2018-11-08 | GSE118306 | GEO

Comparative proteomics analysis of FFPE testicular tissue from men with obstructive and non-obstructive azoospermia

Project description:The project aimed to compare testicular proteomes from patients with obstructive and non-obstructive azoospermia in order to identify molecular signatures involved in spermatogenesis as well to identify candidate biomarkers for discriminating between different types of azoospermia. The samples used in this study were formalin fixed paraffin embedded (FFPE) testicular tissues obtained by biopsy from men with clinical diagnosis of azoospermia. Samples were grouped according to the histopathological report in 3 groups: 1) Spermatogenesis (obstructive azoospermia), 2) Hypospermatogenesis and 3) Sertoli cell only syndrome (SCO). Patients were aged 31–46 years with no differences among groups regarding age (Median age (Hypospermatogenesis) =35; Median age (SCO) =34 and Median age (Spermatogenesis) =39). Each group had 9 samples or 27 samples in total were used for the comparative proteomics analysis by label-free data-independent LC-MS/MS.

2022-07-31 | PXD032722 | Pride

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data