Effects of Pgam1-mediated glycolysis pathway in Sertoli cells on Spermatogonial stem cells based on transcriptomics and energy metabolomics.
Effects of Pgam1-mediated glycolysis pathway in Sertoli cells on Spermatogonial stem cells based on transcriptomics and energy metabolomics.
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基于转录组学和能量代谢组学的PGam1介导的支持细胞糖酵解途径对精原干细胞的影响
DOI：
10.3389/fvets.2022.992877
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发表时间：
2022
影响因子：
3.2
通讯作者：
中科院分区：
文献类型：
--
作者：
精子发生是一个复杂的过程，涉及多种细胞间的相互作用和对基因表达的精确调控。精子发生是由基本的精原干细胞(SSCs)和哺乳动物的睾丸维持的。支持细胞(Sertoli cell，SCs)是SSC生态位的主要组成部分。支持细胞为生殖细胞的发育提供结构支持和能量底物。磷酸甘油酸变位酶1(PGam1)是糖酵解代谢中的关键酶，我们前期的工作表明PGam1在干细胞中有表达。在目前的研究中，假设干细胞中PGam1抑制的糖酵解在调节SSCs命运的决定中起着功能作用。建立小鼠干细胞与原代精原细胞共培养体系，研究PGam1基因敲除或过表达对SSCs增殖和分化的影响。转录组结果显示，PGam1在SCs中的过表达和敲除分别导致458个基因上调(117个下调，341个上调)和409个基因的下调(110个下调，299个上调)。对这些基因的进一步分析表明，GDNF、FGF2和其他在SSCs生态位维持中起关键作用的基因受到PGam1的调控。代谢组学结果表明，在PGam1基因的过表达和敲除中，分别鉴定出11种和16种差异代谢物。对这些代谢产物的进一步筛选表明，Sertoli细胞来源的谷氨酸、谷氨酰胺、苏氨酸、亮氨酸、丙氨酸、赖氨酸、丝氨酸、琥珀酸、富马酸、磷酸烯醇式丙酮酸、ATP、ADP和AMP在调节SSCs的增殖和分化方面具有潜在的作用。综上所述，本研究建立了SCs-SSCs共培养体系，并确定了影响SSCs增殖和分化的基因和小代谢分子。这项研究为哺乳动物精子发生过程中干细胞和干细胞之间相互作用的调节机制提供了更多的见解。
Spermatogenesis is a complex process involving a variety of intercellular interactions and precise regulation of gene expression. Spermatogenesis is sustained by a foundational Spermatogonial stem cells (SSCs) and in mammalian testis. Sertoli cells (SCs) are the major component of SSC niche. Sertoli cells provide structural support and supply energy substrate for developing germ cells. Phosphoglycerate mutase 1 (Pgam1) is a key enzyme in the glycolytic metabolism and our previous work showed that Pgam1 is expressed in SCs. In the present study, hypothesized that Pgam1-depedent glycolysis in SCs plays a functional role in regulating SSCs fate decisions. A co-culture system of murine SCs and primary spermatogonia was constructed to investigate the effects of Pgam1 knockdown or overexpression on SSCs proliferation and differentiation. Transcriptome results indicated that overexpression and knockdown of Pgam1 in SCs resulted in up-regulation of 458 genes (117 down-regulated, 341 up-regulated) and down-regulation of 409 genes (110 down-regulated, 299 up-regulated), respectively. Further analysis of these DEGs revealed that GDNF, FGF2 and other genes that serve key roles in SSCs niche maintenance were regulated by Pgam1. The metabolome results showed that a total of 11 and 16 differential metabolites were identified in the Pgam1 gene overexpression and knockdown respectively. Further screening of these metabolites indicated that Sertoli cell derived glutamate, glutamine, threonine, leucine, alanine, lysine, serine, succinate, fumarate, phosphoenolpyruvate, ATP, ADP, and AMP have potential roles in regulating SSCs proliferation and differentiation. In summary, this study established a SCs-SSCs co-culture system and identified a list of genes and small metabolic molecules that affect the proliferation and differentiation of SSCs. This study provides additional insights into the regulatory mechanisms underlying interactions between SCs and SSCs during mammalian spermatogenesis.
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影响因子：
4.6
作者：
Mateus I;Feijó M;Espínola LM;Vaz CV;Correia S;Socorro S
通讯作者：
Socorro S
影响因子：
2.1
作者：
Gadea, Joaquin;Gumbao, David;Carlos Gardon, Juan
通讯作者：
Carlos Gardon, Juan
影响因子：
2.4
作者：
Hasanein, P.;Fazeli, F.;Roghani, M.
通讯作者：
Roghani, M.
影响因子：
--
作者：
Oliveira, P. F.;Alves, M. G.;Socorro, S.
通讯作者：
Socorro, S.
影响因子：
48
作者：
Mortazavi, Ali;Williams, Brian A.;Wold, Barbara
通讯作者：
Wold, Barbara