کلیدواژهها
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Germline Stem Cells, Regulatory Pathways, Protein-Protein Interaction (PPI) Network, Gene Expression Analysis, Regenerative Medicine
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چکیده
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Male germline stem cells (mGSCs) and female germline stem cells (fGSCs) are crucial for transmitting genetic information to future generations. mGSCs, or spermatogonial stem cells, located in the testes, produce spermatozoa via spermatogenesis. Their key regulatory pathway involves GDNF, activating RET and GFRα1 receptors to promote self-renewal and proliferation. In contrast, fGSCs, or oogonial stem cells, located in the ovaries, participate in oogenesis, regulated by the KIT ligand, its receptor c-KIT, and the PI3K/Akt pathway. Germline stem cells hold significant potential in regenerative medicine and fertility treatments. mGSCs can be used in gene therapy to correct genetic defects before transmission, while fGSCs can generate oocytes for women with diminished ovarian reserves or premature ovarian failure. mGSCs maintain sperm production throughout life, whereas fGSCs' oocyte production declines with age. Understanding these cells' gene transcription profiles and signaling pathways reveals functional differences, paving the way for clinical applications in genetic disease and infertility treatments.
We utilized microarray data (GEO accession number: GSE51313) to identify differentially expressed genes in fGSCs and mGSCs. Using the STRING database, we predicted the protein-protein interaction (PPI) network of adjacent proteins of these genes. Cytoscape and the Gephi app filtered the network's relevant nodes based on parameters. Enrichment analysis highlighted significant pathways and genes. Fluidigm real-time PCR and immunostaining validated our bioinformatics analysis.
We found notable upregulation of Jun, Fos, Sox9, Cdh5, Klf4, and Cxcl12 in fGSCs compared to mGSCs, while Kit, Pou5f1, and Jak2 were significantly downregulated in fGSCs. PPI analysis revealed five clusters with specialized functions. Enrichment analysis underscored critical pathways, including Signal Transduction, Extracellular matrix organization, RET signaling, and Regulation of Insulin-like Gr
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