Presentation number: MG 49

N-GLYCOSYLATION OF INDUCED PLURIPOTENT STEM CELLS (IPSCS) AND NEURAL STEM CELLS (NSCS) DERIVED FROM PERSON WITH DOWN SYNDROME (DS) CAUSED BY TRISOMY 21 (T21)

Dražen Juraj Petrović1,2, Ana Cindrić1, Ivan Alić3,4, Aoife Murray4, Dinko Mitrečić2, Jasminka Krištić1, Tomislav Klarić1, Gordan Lauc1, Dean Nižetić4

1Genos d.o.o., Laboratory for Glycobiology, Zagreb, Croatia, 2Croatian Institute for Brain Research, School of Medicine, University of Zagreb, Histology and Embriology, Zagreb, Croatia, 3Faculty of Veterinary Medicine of University of Zagreb, Anatomy, Histology and Embriology, Zagreb, Croatia, 4The Blizard Institute, Barts and The London School of Medicine, Queen Mary University of London, Genomics and Child Health, London, United Kingdom

The goal was to explore the difference in N-glycosylation between euploid disomic (D21) and trisomic (T21) isogenic human induced pluripotent stem cells (iPSCs) and neural stem cells (NSCs) derived from person with mosaic Down syndrome (DS) trisomy of 21st chromosome. Cell pellets of isogenic disomic and trisomic iPSCs are derived from a person with mosaic DS. Cells were lysed and (glyco)proteins were extracted. N-glycans were released from cell lysates and then fluorescently labeled. After a clean-up by hydrophilic interaction liquid chromatography (HILIC), labeled glycans were obtained and subsequently separated by HILIC-UHPLC (ultra-high performance liquid chromatography). Data was processed into chromatograms which were separated into 45 glycan peaks. Comparison of iPSCs and NSCs using student’s t-test revealed a clear difference in N-glycosylation. There was an increase in the relative abundance of five glycan peaks and a decrease in the abundance of nine glycan peaks in iPSCs when compared to NSCs. Comparison of disomic and trisomic iPSCs revealed no significant difference in the relative abundance of N-glycans. The same was true for disomic and trisomic NSCs. A significant difference was observed in N-glycosylation between isogenic iPSC and NSCs, which falls in line with recently published research that showed NSCs tend to have more N-Glycosylation of NrCAM and different Plexins compared to iPSCs. The lack of differences in N-glycosylation between disomic and trisomic cells might be explained by the small effect of increased gene expression of chromosome 21 during the pluripotent/stem cell stage, but also due to low levels of N-glycosylation in iPSCs (and NSCs).

Key words: N-glycosylation, Down syndrome, isogenic, stem cells

  • OPEN ACCESS

  • PEER REVIEWED

Published: June 21st, 2022;

Copyright: © 2022 ISABS & IAR Publishing. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.