Aberrant proliferation and differentiation of glycogen storage disease type Ib mesenchymal stem cells.

Abstract

Glycogen storage disease type Ib (GSD-Ib) is caused by mutations of the glucose-6-phosphate transporter (G6PT) and characterized by disrupted glucose homeostasis, neutropenia, and neutrophil dysfunction. To investigate the role of G6PT in human adipose-derived mesenchymal stem cells (hMSCs), the G6PT gene was mutated by CRISPR/Cas9 technology and single cell-derived G6PT-/- hMSCs were established. G6PT-/- hMSCs have significantly increased cell proliferation but impaired adipogenesis and osteogenesis. These phenotypes are associated with two mechanisms: i) metabolic reprogramming in G6PT-/- hMSCs causing a metabolic shift toward glycolysis rather than oxidative phosphorylation and ii) increased cyclooxygenase-2-derived prostaglandin E2 secretion in G6PT-/- hMSCs. This study demonstrates that G6PT is essential for proliferation and differentiation of MSCs, providing important insights into the GSD-Ib phenotypes.

• Authors: Sang Wan Sim, Tae Sub Park, Sung-Jo Kim, Byung-Chul Park, David A Weinstein, Young Mok Lee, Hyun Sik Jun
• Journal: FEBS letters (FEBS Lett) Vol. 592 Issue 2 Pg. 162-171 (01 2018) ISSN: 1873-3468 [Electronic] England
• PMID: 29238966 (Publication Type: Letter, Research Support, Non-U.S. Gov't)
• Copyright: © 2017 Federation of European Biochemical Societies.

Chemical References

• Antiporters
• Monosaccharide Transport Proteins
• SLC37A4 protein, human
• Cyclooxygenase 2
• PTGS2 protein, human
• Dinoprostone

Topics

• Adipogenesis
• Adipose Tissue (cytology, metabolism)
• Antiporters (genetics)
• CRISPR-Cas Systems
• Cell Differentiation
• Cell Proliferation
• Cells, Cultured
• Cyclooxygenase 2 (metabolism)
• Dinoprostone (metabolism)
• Glycogen Storage Disease Type I (genetics)
• Glycolysis
• Humans
• Mesenchymal Stem Cells (cytology, metabolism)
• Monosaccharide Transport Proteins (genetics)
• Osteogenesis
• Phenotype
• Single-Cell Analysis