Pompe Disease Results in a Golgi-based Glycosylation Deficit in Human Induced Pluripotent Stem Cell-derived Cardiomyocytes

Raval, Kunil K.; Tao, Ran; White, Brent E.; Lange, Willem J. de; Koonce, Chad H.; Yu, Junying; Kishnani, Priya S.; Thomson, James A.; Mosher, Deane F.; Ralphe, J. Carter; Kamp, Timothy J.

doi:10.1074/jbc.m114.628628

Cited by 78 publications

(70 citation statements)

References 87 publications

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“…In Pompe disease, a lysosomal storage disease characterized by massive accumulation of glycogen, suppression of autophagosome formation by genetic deficiency of ATG7 results in amelioration of the phenotype and facilitates enzyme replacement therapy [55]. However, more recently it was reported that fibroblasts from Pompe patients reprogrammed to a cardiomyocyte lineage exhibit normal contractile properties and preserved autophagic flux [56]. …”

Section: Autophagy In Cardiac Lysosomal Storage Diseasementioning

confidence: 99%

Therapeutic targeting of autophagy in cardiovascular disease

Schiattarella

Hill²

2016

Journal of Molecular and Cellular Cardiology

146

122

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Autophagy is an evolutionarily ancient process of intracellular catabolism necessary to preserve cellular homeostasis in response to a wide variety of stresses. In the case of post-mitotic cells, where cell replacement is not an option, finely tuned quality control of cytoplasmic constituents and organelles is especially critical. And due to the ubiquitous and critical role of autophagic flux in the maintenance of cell health, it comes as little surprise that perturbation of the autophagic process is observed in multiple disease processes. A large body of preclinical evidence suggests that autophagy is a double-edged sword in cardiovascular disease, acting in either beneficial or maladaptive ways, depending on the context. In light of this, the autophagic machinery in cardiomyocytes and other cardiovascular cell types has been proposed as a potential therapeutic target. Here, we summarize current knowledge regarding the dual functions of autophagy in cardiovascular disease. We go on to analyze recent evidence suggesting that titration of autophagic flux holds potential as a novel treatment strategy.

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Section: Autophagy In Cardiac Lysosomal Storage Diseasementioning

confidence: 99%

Therapeutic targeting of autophagy in cardiovascular disease

Schiattarella

Hill²

2016

Journal of Molecular and Cellular Cardiology

146

122

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“…Another emerging area of iPSC disease modeling involves lysosomal storage disorders (LSDs) including Hurler syndrome [94], Pompe disease [95-97], Gaucher disease [98-103], Fabry disease [104], and Niemann-Pick Type C [105]. Each of these storage disorders result from mutations in proteins that facilitate the degradation of particular glycan products.…”

Section: Introductionmentioning

confidence: 99%

Glycosylation and stem cells: Regulatory roles and application of iPSCs in the study of glycosylation‐related disorders

Berger¹,

Dookwah²,

Steet³

et al. 2016

BioEssays

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Glycosylation refers to the co- and post-translational modification of protein and lipids by monosaccharides or oligosaccharide chains. The surface of mammalian cells is decorated by a heterogeneous and highly complex array of protein and lipid linked glycan structures that vary significantly between different cell types, raising questions about their roles in development and disease pathogenesis. This review will begin by focusing on recent findings that define roles for cell surface protein and lipid glycosylation in pluripotent stem cells and their functional impact during normal development. Then, we will describe how patient derived induced pluripotent stem cells are being used to model human diseases such as congenital disorders of glycosylation. Collectively, these studies indicate that cell surface glycans perform critical roles in human development and disease.

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“…Pompe and control hiPSCCMs demonstrated no significant differences in contractile strength, kinetics, or clearance rates of autophagosomes. However, similar to the patients' myocardium, Pompe hiPSCCMs had diminished GAA activity, lysosomal glycogen accumulation, and lysosome enlargement (227). MALDI-TOF-MS analysis of N-linked glycans revealed that Pompe cardiomyopathy could be caused by a glycan-processing abnormality, as often seen in congenital glycosylation disorders with an HCM phenotype, therefore providing mechanistic insight into the disease pathological mechanisms.…”

Section: Metabolic Disordersmentioning

confidence: 97%

Human Induced Pluripotent Stem Cells as a Platform for Personalized and Precision Cardiovascular Medicine

Matsa

Ahrens

2016

Physiological Reviews

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Human induced pluripotent stem cells (hiPSCs) have revolutionized the field of human disease modeling, with an enormous potential to serve as paradigm shifting platforms for preclinical trials, personalized clinical diagnosis, and drug treatment. In this review, we describe how hiPSCs could transition cardiac healthcare away from simple disease diagnosis to prediction and prevention, bridging the gap between basic and clinical research to bring the best science to every patient.

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Pompe Disease Results in a Golgi-based Glycosylation Deficit in Human Induced Pluripotent Stem Cell-derived Cardiomyocytes

Cited by 78 publications

References 87 publications

Therapeutic targeting of autophagy in cardiovascular disease

Therapeutic targeting of autophagy in cardiovascular disease

Glycosylation and stem cells: Regulatory roles and application of iPSCs in the study of glycosylation‐related disorders

Human Induced Pluripotent Stem Cells as a Platform for Personalized and Precision Cardiovascular Medicine

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