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|Title:||Excess of O-linked N-acetylglucosamine modifies human pluripotent stem cell differentiation|
|Citation:||Maury, J.J.P., Chan, K.K.K., Zheng, L., Bardor, M., Choo, A.B.H. (2013-09). Excess of O-linked N-acetylglucosamine modifies human pluripotent stem cell differentiation. Stem Cell Research 11 (2) : 926-937. ScholarBank@NUS Repository. https://doi.org/10.1016/j.scr.2013.06.004|
|Abstract:||O-linked-N-acetylglucosamine (O-GlcNAc), a post translational modification, has emerged as an important cue in controlling key cell mechanisms. Here, we investigate O-GlcNAc's role in the maintenance and differentiation of human pluripotent stem cells (hPSC). We reveal that protein expression of O-GlcNAc transferase and hydrolase both decreases during hPSC differentiation. Upregulating O-GlcNAc with O-GlcNAc hydrolase inhibitors has no significant effect on either the maintenance of pluripotency in hPSC culture, or the loss of pluripotency in differentiating hPSC. However, in spontaneously differentiating hPSC, excess O-GlcNAc alters the expression of specific lineage markers: decrease of ectoderm markers (PAX6 by 53-88%, MSX1 by 26-49%) and increase of adipose-related mesoderm markers (PPARγ by 28-100%, C/EBPα by 46-135%). All other lineage markers tested (cardiac, visceral-endoderm, trophectoderm) remain minimally affected by upregulated O-GlcNAc. Interestingly, we also show that excess O-GlcNAc triggers a feedback mechanism that increases O-GlcNAc hydrolase expression by 29-91%. To the best of our knowledge, this is the first report demonstrating that excess O-GlcNAc does not affect hPSC pluripotency in undifferentiated maintenance cultures; instead, it restricts the hPSC differentiation towards specific cell lineages. These data will be useful for developing targeted differentiation protocols and aid in understanding the effects of O-GlcNAc on hPSC differentiation. © 2013 Elsevier B.V.|
|Source Title:||Stem Cell Research|
|Appears in Collections:||Staff Publications|
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