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| Status |
Public on Dec 17, 2020 |
| Title |
Conserved Spermatogonial Gene Networks Couple to Glutathione and Pentose Phosphate Metabolism but not Cysteine Biosynthesis |
| Organism |
Rattus norvegicus |
| Experiment type |
Expression profiling by high throughput sequencing
Genome binding/occupancy profiling by high throughput sequencing
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| Summary |
Here, gene profiles in rat spermatogonial stem cell lines are compared 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 over-represented 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.
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| Overall design |
Gene expression in rat undifferentiated spermatogonia (USg) vs differentiating spermatogonia (DSg) and spermatocytes (Spc). Foxa2 Chipseq in Rat Undifferentiated Spermatogonia
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| Contributor(s) |
Proki D, Hamra FK |
| Citation(s) |
33458605 |
| Submission date |
Dec 16, 2020 |
| Last update date |
Jan 19, 2021 |
| Contact name |
F. Kent Hamra |
| E-mail(s) |
Kent.Hamra@UTSouthwestern.edu
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| Phone |
214-648-2309
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| Organization name |
UT Southwestern Medical Center
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| Department |
Obstetrics and Gynecology
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| Lab |
Hamra
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| Street address |
5323 Harry Hines Blvd.
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| City |
Dallas |
| State/province |
Texas |
| ZIP/Postal code |
75390 |
| Country |
USA |
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| Platforms (1) |
| GPL18694 |
Illumina HiSeq 2500 (Rattus norvegicus) |
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| Samples (8)
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| Relations |
| BioProject |
PRJNA685730 |
| SRA |
SRP298103 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE163302_RAW.tar |
525.7 Mb |
(http)(custom) |
TAR (of BIGWIG) |
| GSE163302_genes.raw.counts.txt.gz |
178.0 Kb |
(ftp)(http) |
TXT |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data provided as supplementary file |
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