Related Experiment Video
Updated: Jun 9, 2025
Multiplexed Analysis of Retinal Gene Expression and Chromatin Accessibility Using scRNA-Seq and scATAC-Seq
Published on: March 12, 2021
Multi-omics after O-GlcNAc alteration identified cellular processes promoting aneuploidy after loss of O-GlcNAc
Samuel S Boyd1, Dakota R Robarts2, Khue Nguyen3
1Department of Biostatistics and Data Science, University of Kansas Medical Center, Kansas City, KS, USA.
Objective:
Pharmacologic or genetic manipulation of O-GlcNAcylation, an intracellular, single sugar post-translational modification, are difficult to interpret due to the pleotropic nature of O-GlcNAc and the vast signaling pathways it regulates.
Method:
To address the pleotropic nature of O-GlcNAc, we employed either OGT (O-GlcNAc transferase), OGA (O-GlcNAcase) liver knockouts, or pharmacological inhibition of OGA coupled with multi-Omics analysis and bioinformatics.
Results:
We identified numerous genes, proteins, phospho-proteins, or metabolites that were either inversely or equivalently changed between conditions. Moreover, we identified pathways in OGT knockout samples associated with increased aneuploidy. To test and validate these pathways, we induced liver growth in OGT knockouts by partial hepatectomy. OGT knockout livers showed a robust aneuploidy phenotype with disruptions in mitosis, nutrient sensing, protein metabolism/amino acid metabolism, stress response, and HIPPO signaling demonstrating how OGT is essential in controlling aneuploidy pathways.
Conclusion:
These data show how a multi-Omics platform can disentangle the pleotropic nature of O-GlcNAc to discern how OGT fine-tunes multiple cellular pathways involved in aneuploidy.
Insights
Manipulating O-GlcNAcylation is complex. Multi-omics analysis revealed O-GlcNAc transferase (OGT) controls aneuploidy pathways, impacting mitosis and nutrient sensing.
Area of Science:
- Cellular Biology
- Biochemistry
- Genetics
Background:
- O-GlcNAcylation is a crucial post-translational modification regulating numerous cellular pathways.
- The pleotropic nature of O-GlcNAc complicates the interpretation of pharmacologic or genetic manipulation studies.
- Understanding OGT's role is vital for deciphering cellular signaling networks.
Purpose of the Study:
- To investigate the complex roles of O-GlcNAc transferase (OGT) and O-GlcNAcase (OGA) in cellular regulation.
- To disentangle the pleotropic effects of O-GlcNAc using a multi-omics approach.
- To identify specific cellular pathways regulated by OGT, particularly those involved in aneuploidy.
Main Methods:
- Utilized liver knockouts for OGT and OGA in mice.
- Employed pharmacological inhibition of OGA.
- Integrated multi-omics (genomics, proteomics, metabolomics) with bioinformatics analysis.
- Induced liver growth via partial hepatectomy in OGT knockout models for validation.
Main Results:
- Identified numerous genes, proteins, phospho-proteins, and metabolites with altered expression in OGT/OGA manipulation models.
- Discovered pathways associated with increased aneuploidy in OGT knockout samples.
- OGT knockout livers exhibited significant aneuploidy, with disruptions in mitosis, nutrient sensing, protein/amino acid metabolism, stress response, and HIPPO signaling.
Conclusions:
- A multi-omics platform effectively disentangles the pleotropic nature of O-GlcNAc.
- OGT plays an essential role in fine-tuning cellular pathways critical for controlling aneuploidy.
- These findings provide insights into OGT's fundamental role in maintaining genomic stability.
