Importance of evaluating protein glycosylation in pluripotent stem cell-derived cardiomyocytes for research and clinical applications

Maia I. Kelly, Mustafa Albahrani, Chase Castro, Ellen Poon, Bin Yan, Jack Littrell, Matthew Waas, Kenneth R. Boheler, Rebekah L. Gundry

Research output: Contribution to journalReview articlepeer-review

8 Scopus citations


Proper protein glycosylation is critical to normal cardiomyocyte physiology. Aberrant glycosylation can alter protein localization, structure, drug interactions, and cellular function. The in vitro differentiation of human pluripotent stem cells into cardiomyocytes (hPSC-CM) has become increasingly important to the study of protein function and to the fields of cardiac disease modeling, drug testing, drug discovery, and regenerative medicine. Here, we offer our perspective on the importance of protein glycosylation in hPSC-CM. Protein glycosylation is dynamic in hPSC-CM, but the timing and extent of glycosylation are still poorly defined. We provide new data highlighting how observed changes in hPSC-CM glycosylation may be caused by underlying differences in the protein or transcript abundance of enzymes involved in building and trimming the glycan structures or glycoprotein gene products. We also provide evidence that alternative splicing results in altered sites of glycosylation within the protein sequence. Our findings suggest the need to precisely define protein glycosylation events that may have a critical impact on the function and maturation state of hPSC-CM. Finally, we provide an overview of analytical strategies available for studying protein glycosylation and identify opportunities for the development of new bioinformatic approaches to integrate diverse protein glycosylation data types. We predict that these tools will promote the accurate assessment of protein glycosylation in future studies of hPSC-CM that will ultimately be of significant experimental and clinical benefit.

Original languageEnglish (US)
Pages (from-to)1041-1059
Number of pages19
JournalPflugers Archiv European Journal of Physiology
Issue number7
StatePublished - Jul 2021


  • Mass spectrometry
  • Protein glycosylation
  • Stem cell-derived cardiomyocytes

ASJC Scopus subject areas

  • Physiology
  • Clinical Biochemistry
  • Physiology (medical)


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