{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,14]],"date-time":"2026-02-14T06:46:31Z","timestamp":1771051591255,"version":"3.50.1"},"reference-count":52,"publisher":"MDPI AG","issue":"21","license":[{"start":{"date-parts":[[2024,10,30]],"date-time":"2024-10-30T00:00:00Z","timestamp":1730246400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"University of Heidelberg","award":["S-376"],"award-info":[{"award-number":["S-376"]}]},{"name":"University of Heidelberg","award":["Ir.asmt.rec.1403.006"],"award-info":[{"award-number":["Ir.asmt.rec.1403.006"]}]},{"name":"Amol University of Special Modern Technology","award":["S-376"],"award-info":[{"award-number":["S-376"]}]},{"name":"Amol University of Special Modern Technology","award":["Ir.asmt.rec.1403.006"],"award-info":[{"award-number":["Ir.asmt.rec.1403.006"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>The in vitro generation of spermatogonial stem cells (SSCs) from embryonic stem cells (ESCs) offers a viable approach for addressing male infertility. A multitude of molecules participate in this intricate process, which requires additional elucidation. Despite the decline in SSCs in aged testes, SSCs are deemed immortal since they can multiply for three years with repeated transplantation. Nonetheless, the examination of aging is challenging due to the limited quantity and absence of precise indicators. Using a microarray, we assessed genome-wide transcripts (about 55,000 transcripts) of fibroblasts and SSCs. The WGCNA approach was then used to look for SSC-specific transcription factors (TFs) and hub SSC-specific genes based on ATAC-seq, DNase-seq, RNA-seq, and microarray data from the GEO databases as well as gene expression data (RNA-seq and microarray data). The microarray analysis of three human cases with different SSCs revealed that 6 genes were upregulated, and the expression of 23 genes was downregulated compared to the normal case in relation to aging genes. To reach these results, online assessments of Enrich Shiny GO, STRING, and Cytoscape were used to forecast the molecular and functional connections of proteins before identifying the master routes. The biological process and molecular function keywords of cell\u2013matrix adhesion, telomerase activity, and telomere cap complex were shown to be significantly altered in upregulated differentially expressed genes (DEGs) by the functional enrichment analysis. According to our preliminary research, cell-specific TFs and TF-mediated GRNs are involved in the creation of SSCs. In order to maximize the induction efficiency of ESC differentiation into SSCs in vitro, hub SSC-specific genes and important SSC-specific TFs were identified, and sophisticated network regulation was proposed. According to our research, these genes and the hub proteins that they interact with may be able to shine a light on the pathophysiologies of infertility and aberrant germ cells.<\/jats:p>","DOI":"10.3390\/ijms252111653","type":"journal-article","created":{"date-parts":[[2024,10,30]],"date-time":"2024-10-30T12:25:39Z","timestamp":1730291139000},"page":"11653","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Integrating Microarray Data and Single-Cell RNA-Seq Reveals Key Gene Involved in Spermatogonia Stem Cell Aging"],"prefix":"10.3390","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6456-1200","authenticated-orcid":false,"given":"Danial","family":"Hashemi Karoii","sequence":"first","affiliation":[{"name":"Department of Cell and Molecular Biology, School of Biology, College of Science, University of Tehran, Tehran 14174-66191, Iran"},{"name":"Faculty of Biotechnology, Amol University of Special Modern Technologies, Amol 46156-64616, Iran"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8246-595X","authenticated-orcid":false,"given":"Hossein","family":"Azizi","sequence":"additional","affiliation":[{"name":"Faculty of Biotechnology, Amol University of Special Modern Technologies, Amol 46156-64616, Iran"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4813-1213","authenticated-orcid":false,"given":"Thomas","family":"Skutella","sequence":"additional","affiliation":[{"name":"Institute for Anatomy and Cell Biology, Medical Faculty, University of Heidelberg, Im Neuenheimer Feld 307, 69120 Heidelberg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2024,10,30]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Huang, B., Wang, Z., Kong, Y., Jin, M., and Ma, L. 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