2. Academic Validation
  3. A bioenergetic shift is required for spermatogonial differentiation

A bioenergetic shift is required for spermatogonial differentiation

  • Cell Discov. 2020 Aug 18;6:56. doi: 10.1038/s41421-020-0183-x.
Wei Chen 1,  Zhaoran Zhang 2,  Chingwen Chang 2,  Zhichang Yang 3,  Pengxiang Wang 1,  Haihui Fu 4,  Xiao Wei 1,  Eric Chen 2,  Suxu Tan 2,  Wen Huang 2,  Liangliang Sun 3,  Ting Ni 4,  Yi Yang 5,  Yuan Wang 2
Affiliations

Affiliations

  • 1 Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, Shanghai, 200241 China.
  • 2 Department of Animal Sciences, College of Agriculture and Natural Resources, Michigan State University, East Lansing, MI 48824 USA.
  • 3 Department of Chemistry, College of Natural Science, Michigan State University, East Lansing, MI 48824 USA.
  • 4 State Key Laboratory of Genetic Engineering & MOE Key Laboratory of Contemporary Anthropology, Collaborative Innovation Center of Genetics and Development, School of Life Sciences, Fudan University, Shanghai, 200438 China.
  • 5 Synthetic Biology and Biotechnology Laboratory, State Key Laboratory of Bioreactor Engineering, School of Pharmacy, East China University of Science and Technology, Shanghai, 200237 China.
PMID: 32864161 DOI: 10.1038/s41421-020-0183-x
Abstract

A bioenergetic balance between glycolysis and mitochondrial respiration is particularly important for stem cell fate specification. It however remains to be determined whether undifferentiated spermatogonia switch their preference for bioenergy production during differentiation. In this study, we found that ATP generation in spermatogonia was gradually increased upon retinoic acid (RA)-induced differentiation. To accommodate this elevated energy demand, RA signaling concomitantly switched ATP production in spermatogonia from glycolysis to mitochondrial respiration, accompanied by increased levels of Reactive Oxygen Species. Disrupting mitochondrial respiration significantly blocked spermatogonial differentiation. Inhibition of glucose conversion to glucose-6-phosphate or pentose phosphate pathway also repressed the formation of c-Kit+ differentiating germ cells, suggesting that metabolites produced from glycolysis are required for spermatogonial differentiation. We further demonstrated that the expression levels of several metabolic regulators and Enzymes were significantly altered upon RA-induced differentiation, with both RNA-seq and quantitative proteomic analyses. Taken together, our data unveil a critically regulated bioenergetic balance between glycolysis and mitochondrial respiration that is required for spermatogonial proliferation and differentiation.

Keywords

Cell biology; Stem cells.

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