Integrative omics connects N-glycoproteome-wide alterations with pathways and regulatory events in induced pluripotent stem cells.
Molecular-level differences ranging from genomes to proteomes, but not N-glycoproteomes, between human induced pluripotent stem cells (hiPSCs) and embryonic stem cells (hESCs) have been assessed to gain insights into cell reprogramming and induced pluripotency. Our multiplexed quantitative N-glycoproteomics study identified altered N-glycoproteins that significantly regulate cell adhesion processes in hiPSCs compared to hESCs. The integrative proteomics and functional network analyses of the altered N-glycoproteins revealed their significant interactions with known PluriNet (pluripotency-associated network) proteins. We found that these interactions potentially regulate various signaling pathways including focal adhesion, PI3K-Akt signaling, regulation of actin cytoskeleton, and spliceosome. Furthermore, the integrative transcriptomics analysis revealed that imperfectly reprogrammed subunits of the oligosaccharyltransferase (OST) and dolichol-phosphate-mannose synthase (DPM) complexes were potential candidate regulatory events for the altered N-glycoprotein levels. Together, the results of our study suggest that imperfect reprogramming of the protein complexes linked with the N-glycosylation process may result in N-glycoprotein alterations that affect induced pluripotency through their functional protein interactions.
Genomics Research Center, Academia Sinica, Taipei 11529, Taiwan.
Putty-Reddy
PR
Sudhir
Genomics Research Center, Academia Sinica, Taipei 11529, Taiwan.
Madireddy Pavana
MP
Kumari
Institute of Cellular and Organismic Biology, Academia Sinica, Taipei 11529, Taiwan.
Wei-Ting
WT
Hsu
Genomics Research Center, Academia Sinica, Taipei 11529, Taiwan.
Chein-Hung
CH
Chen
Genomics Research Center, Academia Sinica, Taipei 11529, Taiwan.|Institute of Cellular and Organismic Biology, Academia Sinica, Taipei 11529, Taiwan.
Hung-Chih
HC
Kuo
Genomics Research Center, Academia Sinica, Taipei 11529, Taiwan.
Chung-Hsuan
CH
Chen
D002460:Cell Line; D065150:Cellular Reprogramming; D006023:Glycoproteins / Q000378:metabolism*; D000066449:Human Embryonic Stem Cells / Q000378:metabolism; D006801:Humans; D057026:Induced Pluripotent Stem Cells / Q000378:metabolism*; D020543:Proteome / Q000378:metabolism*; D040901:Proteomics / Q000379:methods*; D015398:Signal Transduction; D013194:Staining and Labeling; D059467:Transcriptome / Q000235:genetics
D006023:Glycoproteins; D020543:Proteome