ArticleThe Journal of biological chemistry2012
Heparan sulfate facilitates FGF and BMP signaling to drive mesoderm differentiation 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 51 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
51 citing papers in PubMed, 86 citations in OpenAlex.
- Heparan sulfate as a central modulator of growth factor dynamics in tissue regeneration.APL bioengineering · 2025Article
- Mapping the FGF2 Interactome Identifies a Functional Proteoglycan Coreceptor.ACS chemical biology · 2025Article
- Heparan sulfate regulates the fate decisions of human pluripotent stem cells.Stem cell reports · 2025Article
- Glycosylation in Stem Cell Biology.Handbook of experimental pharmacology · 2025Review
- Heparan Sulfate Chain-Conjugated Laminin-E8 Fragments Advance Paraxial Mesodermal Differentiation Followed by High Myogenic Induction from hiPSCs.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- Vascular Heparan Sulfate and Amyloid-β in Alzheimer's Disease Patients.International journal of molecular sciences · 2024Article
- Glycan Modifications as Regulators of Stem Cell Fate.Biology · 2024Review
- A Spatiotemporal Compartmentalization of Glucose Metabolism Guides Mammalian Gastrulation Progression.bioRxiv : the preprint server for biology · 2023Article
- Human iPSC-derived brain organoids: A 3D mini-brain model for studying HIV infection.Experimental neurology · 2023Article
- Heparan sulfate proteoglycan in Alzheimer's disease: aberrant expression and functions in molecular pathways related to amyloid-β metabolism.American journal of physiology. Cell physiology · 2023Review
- Heparan sulfate proteoglycans in cancer: Pathogenesis and therapeutic potential.Advances in cancer research · 2023Article
- Regulation of stem cell fate by HSPGs: implication in hair follicle cycling.NPJ Regenerative medicine · 2022Review
- Neural progenitor cell-derived extracellular matrix as a new platform for neural differentiation of human induced pluripotent stem cells.Biomaterials and biosystems · 2022Article
- Molecular dynamics-based descriptors of 3-O-Sulfated Heparan sulfate as contributors of protein binding specificity.Computational biology and chemistry · 2022Article
- Dermatan-4-Frontiers in cell and developmental biology · 2021Article
- Heparan Sulfate Facilitates Spike Protein-Mediated SARS-CoV-2 Host Cell Invasion and Contributes to Increased Infection of SARS-CoV-2 G614 Mutant and in Lung Cancer.Frontiers in molecular biosciences · 2021Article
- Proteoglycans and Glycosaminoglycans in Stem Cell Homeostasis and Bone Tissue Regeneration.Frontiers in cell and developmental biology · 2021Review
- An analysis of osteoporosis in patients with hereditary multiple exostoses.Osteoporosis international : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA · 2020Article
- Heparanase promotes myeloma stemness and in vivo tumorigenesis.Matrix biology : journal of the International Society for Matrix Biology · 2020Article
- Heparan sulfate inhibits transforming growth factor β signaling and functions in cis and in trans to regulate prostate stem/progenitor cell activities.Glycobiology · 2020Article
Corrections and comments
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
Abstract
Heparan sulfate (HS) has been implicated in regulating cell fate decisions during differentiation of embryonic stem cells (ESCs) into advanced cell types. However, the necessity and the underlying molecular mechanisms of HS in early cell lineage differentiation are still largely unknown. In this study, we examined the potential of EXT1(-/-) mouse ESCs (mESCs), that are deficient in HS, to differentiate into primary germ layer cells. We observed that EXT1(-/-) mESCs lost their differentiation competence and failed to differentiate into Pax6(+)-neural precursor cells and mesodermal cells. More detailed analyses highlighted the importance of HS for the induction of Brachyury(+) pan-mesoderm as well as normal gene expression associated with the dorso-ventral patterning of mesoderm. Examination of developmental cell signaling revealed that EXT1 ablation diminished FGF and BMP but not Wnt signaling. Furthermore, restoration of FGF and BMP signaling each partially rescued mesoderm differentiation defects. We further show that BMP4 is more prone to degradation in EXT1(-/-) mESCs culture medium compared with that of wild type cells. Therefore, our data reveal that HS stabilizes BMP ligand and thereby maintains the BMP signaling output required for normal mesoderm differentiation. In summary, our study demonstrates that HS is required for ESC pluripotency, in particular lineage specification into mesoderm through facilitation of FGF and BMP signaling.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.