1. Stem Cell Lineage Specification: You Become What You Eat
Clifford D.L. Folmes, Andre Terzic 
Cell Metabolism 
Volume 20, Issue 3, Pages (September 2014)
DOI: /j.cmet
Copyright © 2014 Elsevier Inc. Terms and Conditions

2. Figure 1
Glutamine and Glucose Metabolism Regulates Hematopoietic Stem Cell Lineage Specification
(A) Regulation of glutamine and glucose metabolism defines the ability of hematopoietic stem cells (HSCs) to differentiate into erythroid versus myeloid lineages in vitro and in vivo. Glutamine uptake and glutaminolysis in support of de novo nucleotide biosynthesis and tricarboxylic acid cycle α-ketoglutarate generation are critical for HSC erythroid lineage commitment. Alternative metabolic pathways that support nucleotide synthesis, including 2-deoxyglucose (2-DG) shunting of glucose metabolism away from glycolysis toward the pentose phosphate pathway, promote erythropoiesis.
(B) In contrast, impairing nucleotide biosynthesis during erythropoietin-induced differentiation by impeding upstream glutamine synthesis (methionine sulfoximine, MSO), glutamine uptake, glutaminolysis (6-diao-5-oxo-L-norleucine, DON), transaminase reactions (aminooxyacetic acid, AOA), or blocking glucose entry into the pentose phosphate pathway (6-aminonicotinamide, 6-AN) skews lineage commitment away from erythroid and toward myeloid fate. Supplementation with nucleosides rescues erythropoiesis, establishing the importance of de novo nucleotide biosynthesis for erythroid lineage commitment. GDH, glutamine dehydrogenase; GPAT, glutamine phosphoribosylpyrophosphate amidotransferase; GS, glutamine synthetase; G-6-P, glucose-6-phosphate; G6PD, glucose-6-phosphate dehydrogenase; PRA, phosphoribosylamine; PRPP, 5-phosphoribosyl-1-pyrophosphate.
Cell Metabolism  , DOI: ( /j.cmet )
Copyright © 2014 Elsevier Inc. Terms and Conditions