Embryonic Stem Cell Proliferation Stimulated By Altered Anabolic Metabolism From Glucose Transporter 2-Transported Glucosamine.
The hexose transporter, GLUT2 (SLC2A2), which is expressed by mouse embryos, is important for survival before embryonic day 10.5, but its function in embryos is unknown. GLUT2 can transport the amino sugar glucosamine (GlcN), which could increase substrate for the hexosamine biosynthetic pathway (HBSP) that produces UDP-N-acetylglucosamine for O-linked N-acetylglucosamine modification (O-GlcNAcylation) of proteins. To understand this, we employed a novel murine embryonic stem cell (ESC) line that, like mouse embryos, expresses functional GLUT2 transporters. GlcN stimulated ESC proliferation in a GLUT2-dependent fashion but did not regulate pluripotency. Stimulation of proliferation was not due to increased O-GlcNAcylation. Instead, GlcN decreased dependence of the HBSP on fructose-6-PO4 and glutamine. Consequently, glycolytic- and glutamine-derived intermediates that are needed for anabolic metabolism were increased. Thus, maternally obtained GlcN may increase substrates for biomass accumulation by embryos, as exogenous GlcN does for GLUT2-expressing ESC, and may explain the need for GLUT2 expression by embryos.
Section on Islet Cell and Regenerative Biology Joslin Diabetes Center, Boston, MA 02215, USA.|Department of Medicine, Harvard Medical School, Boston, MA 02115, USA.
Jin Hyuk
JH
Jung
Section on Islet Cell and Regenerative Biology Joslin Diabetes Center, Boston, MA 02215, USA.|Department of Medicine, Harvard Medical School, Boston, MA 02115, USA.
Kumiko
K
Iwabuchi
Section on Islet Cell and Regenerative Biology Joslin Diabetes Center, Boston, MA 02215, USA.|Section on Vascular Cell Biology Harvard Medical School, Boston, MA 02115, USA.
Zhihong
Z
Yang
Section on Islet Cell and Regenerative Biology Joslin Diabetes Center, Boston, MA 02215, USA.|Department of Medicine, Harvard Medical School, Boston, MA 02115, USA.
Mary R
MR
Loeken
D000818:Animals; D001692:Biological Transport; D002460:Cell Line; D049109:Cell Proliferation; D005260:Female; D005944:Glucosamine / Q000502:physiology*; D051273:Glucose Transporter Type 2 / Q000378:metabolism*; D006031:Glycosylation; D008297:Male; D053858:Metabolic Networks and Pathways; D051379:Mice; D000066450:Mouse Embryonic Stem Cells / Q000502:physiology*; D011499:Protein Processing, Post-Translational; D014157:Transcription Factors / Q000378:metabolism
D051273:Glucose Transporter Type 2; C495682:Slc2a2 protein, mouse; D014157:Transcription Factors; D005944:Glucosamine