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Paper of the Month

October’s paper has been proposed by Beata Lecka-Czernik

 

Glutamine Metabolism Regulates Proliferation and Lineage Allocation in Skeletal Stem Cells.

Yilin Yu, Hunter Newman, Leyao Shen, Deepika Sharma, Guoli Hu, Anthony J. Mirando, Hongyuan Zhang, Everett Knudsen, Guo-Fang Zhang, Matthew J. Hilton, Courtney M. Karner

 2019 Apr 2;29(4):966-978.e4. doi: 10.1016/j.cmet.2019.01.016. Epub 2019 Feb 14

 

Skeletal stem cells (SSCs) are postulated to provide a continuous supply of osteoblasts throughout life. However, under certain conditions, the SSC population can become incorrectly specified or is not maintained, resulting in reduced osteoblast formation, decreased bone mass, and in severe cases, osteoporosis. Glutamine metabolism has emerged as a critical regulator of many cellular processes in diverse pathologies. The enzyme glutaminase (GLS) deaminates glutamine to form glutamate-the rate-limiting first step in glutamine metabolism. Using genetic and metabolic approaches, we demonstrate GLS and glutamine metabolism are required in SSCs to regulate osteoblast and adipocyte specification and bone formation. Mechanistically, transaminase-dependent α-ketoglutarate production is critical for the proliferation, specification, and differentiation of SSCs. Collectively, these data suggest stimulating GLS activity may provide a therapeutic approach to expand SSCs in aged individuals and enhance osteoblast differentiation and activity to increase bone mass.