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

First Author  Yu Y Year  2019
Journal  Cell Metab Volume  29
Issue  4 Pages  966-978.e4
PubMed ID  30773468 Mgi Jnum  J:275108
Mgi Id  MGI:6303556 Doi  10.1016/j.cmet.2019.01.016
Citation  Yu Y, et al. (2019) Glutamine Metabolism Regulates Proliferation and Lineage Allocation in Skeletal Stem Cells. Cell Metab 29(4):966-978.e4
abstractText  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 alpha-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.
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