Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

‘Sertoli cell-only’ phenotype and single-cell RNA-seq define PRAMEF12 as a germline-specific factor for male stem cell maintenance and differentiation [RNA-Seq]

ABSTRACT: Spermatogonial stem cells (SSCs) have the dual capacity to self-renew and differentiate into progenitor spermatogonia that develop into mature spermatozoa. Here, we document that preferentially expressed antigen of melanoma family member 12 (PRAMEF12) is a key regulator of germline stem cell maintenance and differentiation. In male mice, genetic ablation of Pramef12 arrests spermatogenesis and results in sterility which can be rescued by transgenic expression of Pramef12. Pramef12 deficiency globally decreases expression of spermatogenic-related genes and single-cell transcriptional analysis of male germline cells identifies four spermatogonial states. In the absence of Pramef12 expression, there are fewer spermatogonial stem cells which exhibit lower expression of SSC maintenance-related genes and are defective in their ability to differentiate. The disruption of the first wave of spermatogenesis in junenile mice results in agametic seminiferous tubules. These observations mimic a ‘Sertoli cell-only’ phenotype in humans and may have translational implications for reproductive medicine.

ORGANISM(S): Mus musculus

PROVIDER: GSE117706 | GEO | 2019/10/22

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Similar Datasets

‘Sertoli cell-only’ phenotype and single-cell RNA-seq define PRAMEF12 as a germline-specific factor for male stem cell maintenance and differentiation [scRNA-seq]

Project description:Spermatogonial stem cells (SSCs) have the dual capacity to self-renew and differentiate into progenitor spermatogonia that develop into mature spermatozoa. Here, we document that preferentially expressed antigen of melanoma family member 12 (PRAMEF12) is a key regulator of germline stem cell maintenance and differentiation. In male mice, genetic ablation of Pramef12 arrests spermatogenesis and results in sterility which can be rescued by transgenic expression of Pramef12. Pramef12 deficiency globally decreases expression of spermatogenic-related genes and single-cell transcriptional analysis of male germline cells identifies four spermatogonial states. In the absence of Pramef12 expression, there are fewer spermatogonial stem cells which exhibit lower expression of SSC maintenance-related genes and are defective in their ability to differentiate. The disruption of the first wave of spermatogenesis in junenile mice results in agametic seminiferous tubules. These observations mimic a ‘Sertoli cell-only’ phenotype in humans and may have translational implications for reproductive medicine.

2019-10-22 | GSE117707 | GEO

Sertoli Cell-Only Syndrome Human Transcriptome Profiling Study

Project description:<p>Sertoli cell-only syndrome is severe form of human male infertility in which most seminiferous tubules appear to lack all spermatogenic cells, including spermatogonial stem cells (SSCs). However, a few small tubule segments of some patients have active spermatogenesis and, thus, functional stem cell niches and SSCs. Normally SSCs replicate, migrate and refill adjacent empty niches, but this does not appear to occur in SCO syndrome. We hypothesized that this failure occurs because most niches are dysfunctional. As Sertoli cells are essential to formation of these niches, we used RNAseq to compare the transcriptomes of human testes with qualitatively normal (complete) spermatogenesis (n=4) with the transcriptomes of human testes with SCO syndrome (n=7). We then focused our analysis on the expression of transcripts that bioinformatic analyses identified as Sertoli cell signature transcripts. Results show that Sertoli cells in SCO testes express abnormally low levels of GDNF, FGF8 and BMP4, all of which are important regulators of mouse SSCs and/or progenitor spermatogonia. Sertoli cells in SCO testes express significantly reduced levels of transcripts for proteins that polarize the Sertoli cell plasma membrane and regulate the trafficking of cell adhesion and gap junction proteins in and out of that plasma membrane.</p>

| phs001777 | dbGaP

Multiomics Approach to Profiling Development of the Spermatogonial Stem Cell Niche Focused on Sertoli cell Maturation

Project description:Spermatogonial stem cells are the foundation of spermatogenesis and as such can serve as a tool for the treatment of infertility in prepubertal cancer survivors. Spermatogonial stem cells are unique as they develop from primordial germ cells (PGCs), which colonize the developing tubules as immature SSC precursors. It has been controversial, when SSCs are maturing to an adult-like stem cell and recent research has found that prepubertal SSCs are actually metabolically distinct from adult SSCs until puberty. Sertoli cells picture a major part of the SSC niche and undergo drastic changes with puberty and polarize to compartmentalize the seminiferous epithelium with formation of tight junctions to a tight basal part where SSCs reside and an apical part with more differentiated stages of spermatogenesis. In the study were mapping the progression of Sertoli cells maturation events to the metabolic changes SSCs undergo during prepubertal development.

2023-02-24 | PXD037764 | Pride

Identification of Glucocorticoid-Induced Leucine Zipper (Gilz) gene targets in undifferentiated spermatogonia

Project description:Sustained spermatogenesis in adult males and recovery of fertility following germ cell depletion are dependent on undifferentiated spermatogonia with self-renewal potential. We have previously demonstrated a critical cell-autonomous role for Gilz in spermatogonial stem cell maintainance and spermatogenesis. To identify genes regulated by Gilz in the male germline, we have isolated undifferentiated spermatogonial cells from tamoxifen treated Gilzflox/flox (Control) and Gilzflox/flox UBC-CreER (TAM-KO) mice that will allow identification of genes mis-expressed upon loss of GILZ.

2018-08-24 | GSE107893 | GEO

Bulk RNA-Seq of whole testis sampled from juvenile mice

Project description:Spermatogenesis is a recurring differentiation process that results in the production of male gametes within the testes. During this process, spermatogonial stem cells differentiate to form spermatocytes, which undergo two rounds of meiotic division to form haploid spermatids. Throughout spermiogenesis, round spermatids elongate to form mature sperm. To profile maturing cell types, we generated bulk RNA-seq data from whole testis undergoing the first round of spermatogenesis between post-natal day P6 and P35. We also compared these libraries to adult samples.

2018-10-09 | E-MTAB-6934 | biostudies-arrayexpress

LRH1 can help reprogram sexual cell fate and is required for Sertoli cell development and spermatogonial stem cell maintenance in the mouse testis

Project description:The mammalian nuclear hormone receptors LRH1 and SF1 are close paralogs that can bind the same DNA site and play crucial roles in gonadal development and function. Lrh1 has been shown to be essential for follicle development in the ovary and also has been proposed to regulate steroidogenesis in the testis, but genetic analysis of its role in the male gonad has not been reported. Here we use conditional genetics to examine Lrh1 requirements in gonadal cell fate reprogramming and in normal development of the three major cell lineages of the mouse testis. Lrh1 expression is highly elevated by loss of the sex regulator Dmrt1, which triggers male-to-female transdifferentiation of Sertoli cells. We found that loss of Lrh1 suppresses this transdifferentiation, confirming that Lrh1 can act as a key driver in reprogramming sexual cell fate. In otherwise wild-type testes we found that Lrh1 is dispensable in Leydig cells but is required in Sertoli cells for their proliferation, for seminiferous tubule morphogenesis, for maintenance of the blood-testis barrier, for feedback regulation of androgen production, and for support of spermatogenesis. Expression profiling identified misexpressed genes likely underlying most aspects of the Sertoli cell phenotype. In the germ line Lrh1 is required for maintenance of spermatogonial stem cells (SSCs) and mutants progressively lose spermatogenesis. Reduced expression of the RNA binding factor Nxf2 likely contributes to the SSC maintenance defect. Unexpectedly, however, the Lrh1 mutant germ line can recover abundant spermatogenesis and fertility. This finding suggests the presence of a reserve stem cell population with different genetic requirements from the stem cells that normally support steady state spermatogenesis. Together our results demonstrate that Lrh1, like Sf1, is an essential regulator of testis development and function but has a distinct repertoire of functions.

2022-02-10 | GSE180204 | GEO

Single-cell RNA sequencing of mouse germ cells

Project description:Spermatogenesis is a recurring differentiation process that results in the production of male gametes within the testes. During this process, spermatogonial stem cells differentiate to form spermatocytes, which undergo two rounds of meiotic division to form haploid spermatids. Throughout spermiogenesis, round spermatids elongate to form mature sperm. To profile maturing germ cells during the first wave of spermatogenesis, we generated droplet-based single cell RNAseq from juvenile animals at post-natal day P5-P35 as well as adult animals. Cells were isolated from whole testes. Furthermore, to assay the robustness of the meiotic cell division process, we profiled germ cells of the trans-chromosomal mouse model (Tc1) that carries a copy of the human chromosome 21.

2019-01-25 | E-MTAB-6946 | biostudies-arrayexpress

Whole transcription data for mouse spermatogonial cells

Project description:Spermatogenesis is a multi-step yet tightly regulated developmental process to produce male gemetes for reproduction. In mouse spermatogenesis, a sub-group of type A spermatogonia (Spga) known as spermatogonial stem cells (SSCs) maintain their population by self-renewal, and differentiate through mitosis and meiosis to form tetraploid (4n) pacchytene spermatocytes (Spcy) and haploid (n) round spermatids (Sptd), which further differentiate into functional sperms. In this study, we selected three representative stages of mouse spermatogenesis, namely Spga, Spcy and Sptd, to study their transcriptomic charteristics using whole genome tiling microarray.

2014-02-27 | GSE55381 | GEO

Whole transcription data for mouse spermatogonial cells

2014-02-27 | E-GEOD-55381 | biostudies-arrayexpress

Molecular and cellular design of ovotestis development

Project description:Ovotestis often occurs in intersex individuals under certain pathological and physiological conditions. However, how ovotestis is formed remains unknown. Here, we report the first comprehensive single-cell developmental atlas of the model fish ovotestis. We provide an overview of ovotestis cell identities and a roadmap of germline, niche, and stem cell development in ovotestis by cell lineage reconstruction and a uniform manifold approximation and projection. We identify common progenitors of germline stem cells with two states, which reveal their bipotential nature to differentiate into both spermatogonial stem cells and female germline stem cells. Moreover, we found that ovotestis infertility was caused by developmental defects in oogenesis owing to dynamic autophagic degradation in female germline cells, and in spermatogenesis due to deficiency of histone-to-protamine replacement in spermatid differentiation. Notably, signaling pathways in gonadal niche cells and their interaction with germline cells synergistically determined cell fates of both male and female germlines in ovotestis. Overall, we reveal a cellular fate map of germline and niche cell development that shapes cell differentiation directions of ovotestis, and provide novel insights into ovotestis development.

2021-04-21 | GSE153961 | GEO

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