Spermatogonial Gene Networks Selectively Couple to Glutathione and Pentose Phosphate Metabolism but Not Cysteine Biosynthesis
| العنوان: | Spermatogonial Gene Networks Selectively Couple to Glutathione and Pentose Phosphate Metabolism but Not Cysteine Biosynthesis |
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| المؤلفون: | Andrew T. Moehlman, David Prokai, Jaideep Chaudhary, Ashutosh Pudasaini, Alexandrea E. Waits, Patrick W. Keller, Mohammed Kanchwala, F. Kent Hamra, Karen M. Chapman, Jesus F. Acevedo, Bruce R. Carr, Xing Chao |
| المصدر: | iScience iScience, Vol 24, Iss 1, Pp 101880-(2021) |
| بيانات النشر: | Elsevier, 2020. |
| سنة النشر: | 2020 |
| مصطلحات موضوعية: | 0301 basic medicine, GPX1, endocrine system, Somatic cell, 02 engineering and technology, Transsulfuration pathway, Pentose phosphate pathway, Biology, GPX4, Article, 03 medical and health sciences, chemistry.chemical_compound, lcsh:Science, reproductive and urinary physiology, Multidisciplinary, GCLM, urogenital system, Systems Biology, Glutathione, Biological Sciences, 021001 nanoscience & nanotechnology, Cell biology, 030104 developmental biology, GCLC, chemistry, lcsh:Q, 0210 nano-technology, Developmental Biology |
| الوصف: | Summary In adult males, spermatogonia maintain lifelong spermatozoa production for oocyte fertilization. To understand spermatogonial metabolism we compared gene profiles in rat spermatogonia to publicly available mouse, monkey, and human spermatogonial gene profiles. Interestingly, rat spermatogonia expressed metabolic control factors Foxa1, Foxa2, and Foxa3. Germline Foxa2 was enriched in Gfra1Hi and Gfra1Low undifferentiated A-single spermatogonia. Foxa2-bound loci in spermatogonial chromatin were overrepresented by conserved stemness genes (Dusp6, Gfra1, Etv5, Rest, Nanos2, Foxp1) that intersect bioinformatically with conserved glutathione/pentose phosphate metabolism genes (Tkt, Gss, Gclc, Gclm, Gpx1, Gpx4, Fth), marking elevated spermatogonial GSH:GSSG. Cystine-uptake and intracellular conversion to cysteine typically couple glutathione biosynthesis to pentose phosphate metabolism. Rat spermatogonia, curiously, displayed poor germline stem cell viability in cystine-containing media, and, like primate spermatogonia, exhibited reduced transsulfuration pathway markers. Exogenous cysteine, cysteine-like mercaptans, somatic testis cells, and ferroptosis inhibitors counteracted the cysteine-starvation-induced spermatogonial death and stimulated spermatogonial growth factor activity in vitro. Graphical Abstract Highlights • Foxa2-bound loci are enriched with spermatogonial stemness genes in the rat germline • Spermatogonial stemness genes couple to glutathione/pentose phosphate pathways • Mammalian spermatogonia are deficient in transsulfuration pathway gene products • Cysteine-like factors counteract spermatogonial ferroptosis in soma-depleted cultures Biological Sciences; Developmental Biology; Systems Biology |
| اللغة: | English |
| تدمد: | 2589-0042 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::d5088fed42a11182e6e0b7c0c59ef568 http://europepmc.org/articles/PMC7797946 |
| Rights: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....d5088fed42a11182e6e0b7c0c59ef568 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 25890042 |
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