The cell surface marker CD36 selectively identifies matured, mitochondria-rich hPSC-cardiomyocytes

Poon, Ellen; Luo, Xiao; Webb, Sarah; Yan, Bin; Zhao, Rui; Wu, Stanley Chun Ming; Yang, Yong; Zhang, Peng; Bai, Hua-Jun; Shao, Jiaofang; Chan, C. T.; Chan, Godfrey Chi Fung; Tsang, Suk Ying; Gundry, Rebekah L.; Huang, Yang; Boheler, Kenneth R.

doi:10.1038/s41422-020-0292-y

Cited by 38 publications

(38 citation statements)

References 13 publications

(15 reference statements)

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“…CD36 is a class B scavenging receptor degraded by MMP-9. CD36 is also a marker of mature cardiomyocytes [ 108 ]. Intact CD36 stimulates neutrophil apoptosis and macrophage phagocytosis [ 91 ].…”

Section: Mmp-9 Signaling In the Proliferation Phasementioning

confidence: 99%

Infarct in the Heart: What’s MMP-9 Got to Do with It?

et al. 2021

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Over the past three decades, numerous studies have shown a strong connection between matrix metalloproteinase 9 (MMP-9) levels and myocardial infarction (MI) mortality and left ventricle remodeling and dysfunction. Despite this fact, clinical trials using MMP-9 inhibitors have been disappointing. This review focuses on the roles of MMP-9 in MI wound healing. Infiltrating leukocytes, cardiomyocytes, fibroblasts, and endothelial cells secrete MMP-9 during all phases of cardiac repair. MMP-9 both exacerbates the inflammatory response and aids in inflammation resolution by stimulating the pro-inflammatory to reparative cell transition. In addition, MMP-9 has a dual effect on neovascularization and prevents an overly stiff scar. Here, we review the complex role of MMP-9 in cardiac wound healing, and highlight the importance of targeting MMP-9 only for its detrimental actions. Therefore, delineating signaling pathways downstream of MMP-9 is critical.

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Section: Mmp-9 Signaling In the Proliferation Phasementioning

confidence: 99%

Infarct in the Heart: What’s MMP-9 Got to Do with It?

et al. 2021

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“…Among published data, we report that CD36 represents a marker of matured, mitochondria-rich hPSC-CM that is largely absent from undifferentiated hPSC and early hPSC-CM [84]. The extracellular domain of CD36 is predicted to contain 10 N-glycosylation sites (UniProt), including some that are critical for trafficking to the surface membrane [38] and biological function [57].…”

Section: Human Pluripotent Stem Cell-derived Cardiomyocytes and Protein Glycosylationmentioning

confidence: 99%

“…Application of the CSC technology to hPSC-CM collected from 18 experiments on 9 timepoints between days 10 and 93 of differentiation resulted in the identification of 627 cell surface N-glycoproteins identified in at least two experiments (methods described in [84]). RNA-seq analyses were performed on hPSC-CM collected from four timepoints of differentiation, days 15, 30, 45, and 60.…”

Section: Exploring Dynamic Protein Glycosylation Throughout Hpsc-cm Differentiationmentioning

confidence: 99%

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

Kelly

Albahrani

Castro

et al. 2021

Pflugers Arch - Eur J Physiol

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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.

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“…Human pluripotent stem cell‐derived cardiomyocytes retain a fetal phenotype in structure and function, including small cell size, disorganized sarcomere structures, underdeveloped calcium handling, as well as weak excitability, contractility, and adrenergic sensitivity 40‐42 . In addition, the hPSC‐CMs are heterogeneous and display a certain level of experimental variability in maturation 43 . The maturity level of hPSC‐CMs would affect engraftment, proliferation, and therapeutic efficacy in the host hearts 44,45 .…”

Section: Hpsc‐derived Cardiomyocytes For Infarct Repairmentioning

confidence: 99%

“…Moreover, immunophenotyping is one validated approach to overcome cell heterogeneity and experimental variability. We newly identified CD36 as a cell surface marker of maturation in hPSC‐CMs, which can be used to reduce the heterogeneity and experimental variability of hPSC‐CMs to facilitate their application 43 . To facilitate the widespread adoption, maturation‐enhancing approaches that are more scalable, cost‐effective, and capable of independent replication across laboratories need to be developed, such as using small molecules to regulate key steps of mitochondrial biogenesis and metabolism at the critical time window 44 …”

Section: Hpsc‐derived Cardiomyocytes For Infarct Repairmentioning

confidence: 99%

Perspective on human pluripotent stem cell-derived cardiomyocytes in heart disease modeling and repair

Wang

et al. 2020

Stem Cells Translational Medicine

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Heart diseases (HDs) are the leading cause of morbidity and mortality worldwide. Despite remarkable clinical progress made, current therapies cannot restore the lost myocardium, and the correlation of genotype to phenotype of many HDs is poorly modeled. In the past two decades, with the rapid developments of human pluripotent stem cell (hPSC) biology and technology that allow the efficient preparation of cardiomyocytes from individual patients, tremendous efforts have been made for using hPSC-derived cardiomyocytes in preclinical and clinical cardiac therapy as well as in dissection of HD mechanisms to develop new methods for disease prediction and treatment. However, their applications have been hampered by several obstacles. Here, we discuss recent advances, remaining challenges, and the potential solutions to advance this field.

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The cell surface marker CD36 selectively identifies matured, mitochondria-rich hPSC-cardiomyocytes

Cited by 38 publications

References 13 publications

Infarct in the Heart: What’s MMP-9 Got to Do with It?

Infarct in the Heart: What’s MMP-9 Got to Do with It?

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

Perspective on human pluripotent stem cell-derived cardiomyocytes in heart disease modeling and repair

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