AsianScientist (Jan. 9, 2017) – Researchers have found that the Myc gene regulates the self-renewal of mouse spermatogonial stem cells (SSC) by controlling glycolysis, the release of energy via the breakdown of glucose. Their findings, published in Genes & Development, could shed light on why male fertility diminishes with age and possibly lead to new treatments for infertility.
“The so-called Myc genes play an important role in stem cells’ ability to self-renew,” explained Kyoto University’s Professor Takashi Shinohara. He adds that SSCs are unique, because they are “the only stem cells that transmit genetic information to offspring.”
Shinohara and his team injected two types of SSCs into mouse testes: normal cells and Myc gene-deficient cells. Two months later, they found that mice that received Myc-deficient SSCs had a lower capacity for self renewal, with possibly important implications for sperm production.
“We found changes in the expression of genes that would slow the cell cycle,” said Shinohara.
In other words, Myc-deficient SSCs could self-renew, but at a slower than normal rate. Further study showed that this diminished rate was accompanied by impaired glycolysis, suggesting that the cells were not generating sufficient energy.
“A difference in glycolysis could explain natural differences in SSC self-renewal between mice,” said Assistant Professor Mito Kanatsu-Shinohara, first-author of the paper. “DBA/2 and B6 are two mouse types in which SSCs are know to self-renew at different rates.”
Further experiments confirmed that glycolysis was more active in the cells of DBA/2 mice. Moreover, isolating cells from B6 mice and treating them with chemicals that enhanced glycolysis increased the SSC proliferation rate to levels comparable with DBA/2.
“These findings could have important implications for infertility research in the future,” said Shinohara. “Stimulating the metabolism of SSCs could improve their proliferation. However, more careful study of the molecular pathways is necessary.”
The article can be found at: Kanatsu-Shinohara et al. (2016) Myc/Mycn-mediated Glycolysis Enhances Mouse Spermatogonial Stem Cell Self-renewal.
Source: Kyoto University.
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