Metabolic Transitions Define the Spermatogonial Stem Cell Maturation
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ABSTRACT:
PROVIDER: PRJNA807358 | ENA |
REPOSITORIES: ENA
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Project description:Metabolic Transitions Define the Spermatogonial Stem Cell Maturation [mouse]
| PRJNA807336 | ENA
Project description:Metabolic Transitions Define the Spermatogonial Stem Cell Maturation [human]
| PRJNA807362 | ENA
Project description:Spermatogonial stem cells (SSCs) are the basis of spermatogenesis and therefore of male fertility. Transplantation of SSCs, isolated before treatment for cancer, and cultured in vitro, could be a potential treatment for infertility. Such clinical usage requires an understanding of the metabolic requirements during SSC development. Adult SSCs mainly use glycolysis for their maintenance in the mouse and human. However, SSCs embryonic precursors, primordial germ cells (PGCs), require a high mitochondrial metabolism in the mouse. Similarly, pig neonatal SSC precursors have been described to rely on oxidative phosphorylation (OXPHOS) for the first 2 months of development, when a transition to an adult SSC metabolic phenotype is initiated. When and if such a metabolic transition occurs in humans is ambiguous. We show here for the first time using single-cell RNA sequencing, that human PGCs and prepubertal human spermatogonia have an enrichment of oxidative phosphorylation associated genes, which is downregulated by 13 years of age. Furthermore, we show, that similar metabolic differences are detectable after birth also in mouse. The metabolic transition in humans with puberty was preceded by a drastic change of SSC shape. Using a pig model, we reveal that these metabolic changes could be regulated by IGF-1 dependent signaling via mTOR and proteasomic inhibition. Understanding the metabolic requirements of SSCs during development is crucial to establish a culture system and enable clinical use of SSCs.
2022-07-20 | GSE196817 | GEO
Project description:Spermatogonial stem cells (SSCs) are the basis of spermatogenesis and therefore of male fertility. Transplantation of SSCs, isolated before treatment for cancer, and cultured in vitro, could be a potential treatment for infertility. Such clinical usage requires an understanding of the metabolic requirements during SSC development. Adult SSCs mainly use glycolysis for their maintenance in the mouse and human. However, SSCs embryonic precursors, primordial germ cells (PGCs), require a high mitochondrial metabolism in the mouse. Similarly, pig neonatal SSC precursors have been described to rely on oxidative phosphorylation (OXPHOS) for the first 2 months of development, when a transition to an adult SSC metabolic phenotype is initiated. When and if such a metabolic transition occurs in humans is ambiguous. We show here for the first time using single-cell RNA sequencing, that human PGCs and prepubertal human spermatogonia have an enrichment of oxidative phosphorylation associated genes, which is downregulated by 13 years of age. Furthermore, we show, that similar metabolic differences are detectable after birth also in mouse. The metabolic transition in humans with puberty was preceded by a drastic change of SSC shape. Using a pig model, we reveal that these metabolic changes could be regulated by IGF-1 dependent signaling via mTOR and proteasomic inhibition. Understanding the metabolic requirements of SSCs during development is crucial to establish a culture system and enable clinical use of SSCs.
2022-07-20 | GSE196801 | GEO
Project description: Not available
| S-EPMC9614685 | biostudies-literature
Project description:This SuperSeries is composed of the SubSeries listed below.
2022-07-20 | GSE196819 | GEO
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
Project description:Coordinated metabolic transitions and gene expression by NAD+ during adipogenesis.
| PRJNA739727 | ENA
Project description:Spheroid formation during epithelial ovarian cancer progression correlates with peritoneal organ colonization, disease recurrence, and poor prognosis. Although cancer progression has been demonstrated to be associated with and driven by metabolic changes within transformed cells, possible associations between metabolic dynamics and metastatic morphological transitions remain unexplored. To address this problem, performed quantitative proteomics was performed to identify protein signatures associated with three distinct morphologies (2D monolayers and two geometrically individual three-dimensional spheroidal states) of the high-grade serous ovarian cancer line OVCAR-3. Integrating the protein states into genome-scale metabolic models allowed the construction of context-specific metabolic models for each morphological stage of the OVCAR-3 cell line and systematically evaluate their metabolic functionalities.
2023-09-07 | PXD045194 | Pride
Project description:In vitro and in vivo aging of mouse spermatogonial stem cells alters stem cell function based on quantitative spermatogonial stem cell transplantation analyses. We used microarrays to identify differential gene expression in vitro and in vivo aged spermatogonial stem cells to identify potential causes of observed phenotypic differences in aged spermatogonial stem cell function. Spermatogonial stem cells were isolated from young and serial-transplanted aged mouse donors and cultured for short and long periods. Spermatogonial stem cells were isolated from cultures and subjected to microarray analysis to identify differential gene expression.
2011-02-04 | E-GEOD-27043 | biostudies-arrayexpress