Spermatogonial Gene Networks Selectively Couple to Glutathione and Pentose Phosphate Metabolism but Not Cysteine Biosynthesis.
Spermatogonial Gene Networks Selectively Couple to Glutathione and Pentose Phosphate Metabolism but Not Cysteine Biosynthesis.
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DOI：
10.1016/j.isci.2020.101880
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发表时间：
2021-01-22
期刊：
影响因子：
5.8
通讯作者：
Hamra FK
中科院分区：
文献类型：
--
作者：
Prokai D;Pudasaini A;Kanchwala M;Moehlman AT;Waits AE;Chapman KM;Chaudhary J;Acevedo J;Keller P;Chao X;Carr BR;Hamra FK
在成年男性中，精原细胞维持终生精子生成以供卵母细胞受精。为了了解精原细胞代谢，我们将大鼠精原细胞的基因图谱与公开的小鼠、猴子和人类精原细胞基因图谱进行了比较。有趣的是，大鼠精原细胞表达代谢控制因子 Foxa1、Foxa2 和 Foxa3。种系 Foxa2 在 Gfra1Hi 和 Gfra1Low 未分化 A-单精原细胞中富集。精原染色质中的 Foxa2 结合位点被保守的干性基因（Dusp6、Gfra1、Etv5、Rest、Nanos2、Foxp1）过度代表，这些基因在生物信息学上与保守的谷胱甘肽/磷酸戊糖代谢基因（Tkt、Gss、Gclc、Gclm、Gpx1、Gpx4、Fth）交叉，标记精原细胞 GSH:GSSG 升高。胱氨酸的摄取和细胞内转化为半胱氨酸通常将谷胱甘肽生物合成与磷酸戊糖代谢结合起来。奇怪的是，大鼠精原细胞在含胱氨酸的培养基中表现出较差的生殖干细胞活力，并且与灵长类精原细胞一样，表现出转硫途径标记物减少。外源性半胱氨酸、半胱氨酸样硫醇、体细胞睾丸细胞和铁死亡抑制剂可以抵消半胱氨酸饥饿诱导的精原细胞死亡，并刺激体外精原细胞生长因子活性。 Foxa2 结合位点在大鼠种系中富含精原细胞干性基因 精原细胞干性基因与谷胱甘肽/戊糖磷酸途径偶联 哺乳动物精原细胞缺乏转硫途径基因产物 半胱氨酸样因子可抵消体细胞耗尽培养物中的精原细胞铁死亡 生物科学；发育生物学；系统生物学
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. 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
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DOI：
10.1073/pnas.0508780102
发表时间：
2005-11-29
影响因子：
11.1
作者：
Hamra, FK;Chapman, KM;Garbers, DL
通讯作者：
Garbers, DL
影响因子：
44.1
作者：
Guo J;Grow EJ;Mlcochova H;Maher GJ;Lindskog C;Nie X;Guo Y;Takei Y;Yun J;Cai L;Kim R;Carrell DT;Goriely A;Hotaling JM;Cairns BR
通讯作者：
Cairns BR
影响因子：
25
作者：
Aoyama, K;Suh, SW;Swanson, RA
通讯作者：
Swanson, RA
影响因子：
5.9
作者：
Garbuzov A;Pech MF;Hasegawa K;Sukhwani M;Zhang RJ;Orwig KE;Artandi SE
通讯作者：
Artandi SE
影响因子：
3.6
作者：
Abid, Shadaan N.;Richardson, Timothy E.;Hamra, F. Kent
通讯作者：
Hamra, F. Kent