Small Molecule Antagonist of Cell Surface Glycosaminoglycans Restricts Mouse Embryonic Stem Cells in a Pluripotent State

Huang, Mia L.; Michalak, Austen L; Fisher, Christopher J.; Christy, Mitchell P.; Smith, Raymond A.; Godula, Kamil

doi:10.1002/stem.2714

Cited by 15 publications

(21 citation statements)

References 57 publications

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“…The classical targets for these molecules are growth factor receptors or their associated downstream kinases that regulate intracellular signaling pathways during differentiation. For example, a small-molecule antagonist of cell-surface glycosaminoglycans promotes a pluripotent state in mouse ESCs, providing a powerful new alternative to previously existing techniques for controlling stem cell fate [149].…”

Section: Inducting and Enhancing Pluripotency In Ipscs Using Chemicalsmentioning

confidence: 99%

Advances in Pluripotent Stem Cells: History, Mechanisms, Technologies, and Applications

Liu

David

Trawczynski

et al. 2019

Stem Cell Rev and Rep

352

209

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Over the past 20 years, and particularly in the last decade, significant developmental milestones have driven basic, translational, and clinical advances in the field of stem cell and regenerative medicine. In this article, we provide a systemic overview of the major recent discoveries in this exciting and rapidly developing field. We begin by discussing experimental advances in the generation and differentiation of pluripotent stem cells (PSCs), next moving to the maintenance of stem cells in different culture types, and finishing with a discussion of three-dimensional (3D) cell technology and future stem cell applications. Specifically, we highlight the following crucial domains: 1) sources of pluripotent cells; 2) next-generation in vivo direct reprogramming technology; 3) cell types derived from PSCs and the influence of genetic memory; 4) induction of pluripotency with genomic modifications; 5) construction of vectors with reprogramming factor combinations; 6) enhancing pluripotency with small molecules and genetic signaling pathways; 7) induction of cell reprogramming by RNA signaling; 8) induction and enhancement of pluripotency with chemicals; 9) maintenance of pluripotency and genomic stability in induced pluripotent stem cells (iPSCs); 10) feeder-free and xenon-free culture environments; 11) biomaterial applications in stem cell biology; 12) three-dimensional (3D) cell technology; 13) 3D bioprinting; 14) downstream stem cell applications; and 15) current ethical issues in stem cell and regenerative medicine. This review, encompassing the fundamental concepts of regenerative medicine, is intended to provide a comprehensive portrait of important progress in stem cell research and development. Innovative technologies and real-world applications are emphasized for readers interested in the exciting, promising, and challenging field of stem cells and those seeking guidance in planning future research direction.

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Section: Inducting and Enhancing Pluripotency In Ipscs Using Chemicalsmentioning

confidence: 99%

Advances in Pluripotent Stem Cells: History, Mechanisms, Technologies, and Applications

Liu

David

Trawczynski

et al. 2019

Stem Cell Rev and Rep

352

209

View full text Add to dashboard Cite

show abstract

“…both Chinese hamster ovary and mouse embryonic stem cells (20,38). ERK and Akt activation are associated with increased proliferation and with enhanced tumorigenicity, stemness, and invasiveness of GBM (29).…”

Section: Discussionmentioning

confidence: 99%

Surfen‐mediated blockade of extratumoral chondroitin sulfate glycosaminoglycans inhibits glioblastoma invasion

Logun

Wynens

Simchick³

et al. 2019

The FASEB Journal

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Invasive spread of glioblastoma (GBM) is linked to changes in chondroitin sulfate (CS) proteoglycan (CSPG)‐associated sulfated glycosaminoglycans (GAGs) that are selectively up‐regulated in the tumor microenvironment (TME). We hypothesized that inhibiting CS‐GAG signaling in the TME would stem GBM invasion. Rat F98 GBM cells demonstrated enhanced preferential cell invasion into oversulfated 3‐dimensional composite of CSA and CS‐E [4‐ and 4,6‐sulfated CS‐GAG (COMP)] matrices compared with monosulfated (4‐sulfated) and unsulfated hyaluronic acid matrices in microfluidics‐based choice assays, which is likely influenced by differential GAG receptor binding specificities. Both F98 and human patient‐derived glioma stem cells (GSCs) demonstrated a high degree of colocalization of the GSC marker CD133 and CSPGs. The small molecule sulfated GAG antagonist bis‐2‐methyl‐4‐amino‐quinolyl‐6‐carbamide (surfen) reduced invasion and focal adhesions in F98 cells encapsulated in COMP matrices and blocked CD133 and antichondroitin sulfate antibody (CS‐56) detection of respective antigens in F98 cells and human GSCs. Surfen‐treated F98 cells down‐regulated CSPG‐binding receptor transcripts and protein, as well as total and activated ERK and protein kinase B. Lastly, rats induced with frontal lobe tumors and treated with a single intratumoral dose of surfen demonstrated reduced tumor burden and spread compared with untreated controls. These results present a first demonstration of surfen as an inhibitor of sulfated GAG signaling to stem GBM invasion.—Logun, M. T., Wynens, K. E., Simchick, G., Zhao, W., Mao, L., Zhao, Q., Mukherjee, S., Brat, D. J., Karumbaiah, L. Surfen‐mediated blockade of extratumoral chondroitin sulfate glycosaminoglycans inhibits glioblastoma invasion. FASEB J. 33, 11973‐11992 (2019). http://www.fasebj.org

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“…Surfen, a non-specific heparan sulfate antagonist interferes with numerous biological processes, showing potential as a therapeutic agent. The properties of surfen ranges from anti-inflammatory (Warford et al, 2018) and immuomodulatory (Warford et al, 2014) to suppression of stem cell differentiation (Huang et al, 2018), inhibition of HIV type 1 infection (Roan et al, 2010) and rescue of tauopathy in a zebrafish model (Alavi Naini et al, 2018). However, non-specificity limits the beneficial effects of surfen.…”

Section: Heparan Sulfate Proteoglycansmentioning

confidence: 99%

Heparan Sulfate as a Therapeutic Target in Tauopathies: Insights From Zebrafish

Soussi-Yanicostas

2018

Front. Cell Dev. Biol.

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Microtubule-associated protein tau (MAPT) hyperphosphorylation and aggregation, are two hallmarks of a family of neurodegenerative disorders collectively referred to as tauopathies. In many tauopathies, including Alzheimer’s disease (AD), progressive supranuclear palsy (PSP) and Pick’s disease, tau aggregates are found associated with highly sulfated polysaccharides known as heparan sulfates (HSs). In AD, amyloid beta (Aβ) peptide aggregates associated with HS are also characteristic of disease. Heparin, an HS analog, promotes misfolding, hyperphosphorylation and aggregation of tau protein in vitro. HS also provides cell surface receptors for attachment and uptake of tau seeds, enabling their propagation. These findings point to HS-tau interactions as potential therapeutic targets in tauopathies. The zebrafish genome contains genes paralogous to MAPT, genes orthologous to HS biosynthetic and chain modifier enzymes, and other genes implicated in AD. The nervous system in the zebrafish bears anatomical and chemical similarities to that in humans. These homologies, together with numerous technical advantages, make zebrafish a valuable model for investigating basic mechanisms in tauopathies and identifying therapeutic targets. Here, we comprehensively review current knowledge on the role of HSs in tau pathology and HS-targeting therapeutic approaches. We also discuss novel insights from zebrafish suggesting a role for HS 3-O-sulfated motifs in tau pathology and establishing HS antagonists as potential preventive agents or therapies for tauopathies.

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Small Molecule Antagonist of Cell Surface Glycosaminoglycans Restricts Mouse Embryonic Stem Cells in a Pluripotent State

Cited by 15 publications

References 57 publications

Advances in Pluripotent Stem Cells: History, Mechanisms, Technologies, and Applications

Advances in Pluripotent Stem Cells: History, Mechanisms, Technologies, and Applications

Surfen‐mediated blockade of extratumoral chondroitin sulfate glycosaminoglycans inhibits glioblastoma invasion

Heparan Sulfate as a Therapeutic Target in Tauopathies: Insights From Zebrafish

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