ArticleThe Journal of biological chemistry2012
Undersulfation of heparan sulfate restricts differentiation potential of mouse embryonic stem cells.
Article in The Journal of biological chemistry, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
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Who cites it
32 citing papers in PubMed, 64 citations in OpenAlex.
- Glycosaminoglycans in tissue regeneration: Insights into glycobiology and their biomedical application.Bioactive materials · 2026Review
- Glycan Modifications as Regulators of Stem Cell Fate.Biology · 2024Review
- HS, an Ancient Molecular Recognition and Information Storage Glycosaminoglycan, Equips HS-Proteoglycans with Diverse Matrix and Cell-Interactive Properties Operative in Tissue Development and Tissue Function in Health and Disease.International journal of molecular sciences · 2023Review
- Chemistry and Function of Glycosaminoglycans in the Nervous System.Advances in neurobiology · 2023Review
- Physiology and Pathophysiology of Heparan Sulfate in Animal Models: Its Biosynthesis and Degradation.International journal of molecular sciences · 2022Review
- Sulfation Pathways During Neurodevelopment.Frontiers in molecular biosciences · 2022Review
- Proteoglycans and Glycosaminoglycans in Stem Cell Homeostasis and Bone Tissue Regeneration.Frontiers in cell and developmental biology · 2021Review
- Cerebellar Morphology and Behavioral Profiles in Mice Lacking Heparan SulfateJournal of developmental biology · 2020Article
- Heparanase promotes myeloma stemness and in vivo tumorigenesis.Matrix biology : journal of the International Society for Matrix Biology · 2020Article
- Syndecan-1 Facilitates the Human Mesenchymal Stem Cell Osteo-Adipogenic Balance.International journal of molecular sciences · 2020Article
- Heparan Sulfate Proteoglycans: Key Mediators of Stem Cell Function.Frontiers in cell and developmental biology · 2020Review
- Proteoglycans in Obesity-Associated Metabolic Dysfunction and Meta-Inflammation.Frontiers in immunology · 2020Review
- The neutralization of heparan sulfate by heparin-binding copolymer as a potential therapeutic target.RSC advances · 2019Article
- Silencing glycosaminoglycan functions in mouse embryonic stem cells with small molecule antagonists.Methods in enzymology · 2019Article
- Downstream Products are Potent Inhibitors of the Heparan Sulfate 2-O-Sulfotransferase.Scientific reports · 2018Article
- Heparan Sulfate Proteoglycans as Drivers of Neural Progenitors Derived From Human Mesenchymal Stem Cells.Frontiers in molecular neuroscience · 2018Article
- Glycans define the stemness of naïve and primed pluripotent stem cells.Glycoconjugate journal · 2017Review
- Sulfated glycosaminoglycans: their distinct roles in stem cell biology.Glycoconjugate journal · 2017Review
- Heparan sulfate proteoglycans as key regulators of the mesenchymal niche of hematopoietic stem cells.Glycoconjugate journal · 2017Review
- Dynamic changes in heparan sulfate during muscle differentiation and ageing regulate myoblast cell fate and FGF2 signalling.Matrix biology : journal of the International Society for Matrix Biology · 2017Article
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Heparan sulfate proteoglycans, present on cell surfaces and in the extracellular matrix, interact with growth factors and morphogens to influence growth and differentiation of cells. The sulfation pattern of the heparan sulfate chains formed during biosynthesis in the Golgi compartment will determine the interaction potential of the proteoglycan. The glucosaminyl N-deacetylase/N-sulfotransferase (NDST) enzymes have a key role during biosynthesis, greatly influencing total sulfation of the heparan sulfate chains. The differentiation potential of mouse embryonic stem cells lacking both NDST1 and NDST2 was studied using in vitro differentiation protocols, expression of differentiation markers, and assessment of the ability of the cells to respond to growth factors. The results show that NDST1 and NDST2 are dispensable for mesodermal differentiation into osteoblasts but necessary for induction of adipocytes and neural cells. Gene expression analysis suggested a differentiation block at the primitive ectoderm stage. Also, GATA4, a primitive endoderm marker, was expressed by these cells. The addition of FGF4 or FGF2 together with heparin rescued the differentiation potential to neural progenitors and further to mature neurons and glia. Our results suggest that the embryonic stem cells lacking both NDST1 and NDST2, expressing a very low sulfated heparan sulfate, can take the initial step toward differentiation into all three germ layers. Except for their potential for mesodermal differentiation into osteoblasts, the cells are then arrested in a primitive ectoderm and/or endoderm stage.
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