Glycolipid dynamics in generation and differentiation of induced pluripotent stem cells

Ojima, Takuma; Shibata, Eri; Saito, Shuntaro; Toyoda, Masashi; Nakajima, Hideki; Yamazaki-Inoue, Mayu; Miyagawa, Yoshitaka; Kiyokawa, Nobutaka; Fujimoto, Jun; Sato, Toshinori; Umezawa, Akihiro

doi:10.1038/srep14988

Cited by 22 publications

(18 citation statements)

References 29 publications

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“…Oct3/4, Sox2, Klf4, and c-Myc) is sufficient to induce Gb3S expression and globo-series GSL production, implicating a role for stemness factors in the control of Gb3S expression (Ojima et al, 2015). the globo-series GSL drop) in neural differentiation is not known.…”

Section: Discussionmentioning

confidence: 98%

Glycosphingolipid metabolic reprogramming drives neural differentiation

et al. 2017

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Neural development is accomplished by differentiation events leading to metabolic reprogramming. Glycosphingolipid metabolism is reprogrammed during neural development with a switch from globo- to ganglio-series glycosphingolipid production. Failure to execute this glycosphingolipid switch leads to neurodevelopmental disorders in humans, indicating that glycosphingolipids are key players in this process. Nevertheless, both the molecular mechanisms that control the glycosphingolipid switch and its function in neurodevelopment are poorly understood. Here, we describe a self-contained circuit that controls glycosphingolipid reprogramming and neural differentiation. We find that globo-series glycosphingolipids repress the epigenetic regulator of neuronal gene expression AUTS2. AUTS2 in turn binds and activates the promoter of the first and rate-limiting ganglioside-producing enzyme GM3 synthase, thus fostering the synthesis of gangliosides. By this mechanism, the globo-AUTS2 axis controls glycosphingolipid reprogramming and neural gene expression during neural differentiation, which involves this circuit in neurodevelopment and its defects in neuropathology.

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Section: Discussionmentioning

confidence: 98%

Glycosphingolipid metabolic reprogramming drives neural differentiation

et al. 2017

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“…The high abundance of α1-2 fucosylated glycans is one of the most striking factors that distinguishes hPSCs from differentiated cell types [30, 31, 34, 36, 38, 43, 44]. Increased expression of FUT1 and FUT2 genes, which encode enzymes that catalyze the linkage between fucose and its acceptor protein through an α1-2 linkage, accounts for elevated fucosylation although other regulatory steps are likely to contribute as well [25, 30, 32, 34, 43, 44].…”

Section: Introductionmentioning

confidence: 99%

“…Increased expression of FUT1 and FUT2 genes, which encode enzymes that catalyze the linkage between fucose and its acceptor protein through an α1-2 linkage, accounts for elevated fucosylation although other regulatory steps are likely to contribute as well [25, 30, 32, 34, 43, 44]. These findings contrast with previous studies in murine PSCs where α1-2 fucosylation is not prevalent, highlighting potential differences in glycosylation patterns between the two species [13, 33].…”

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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“…This epitope is present on two unidentified glycolipid antigens and phosphacan, a chondroitan sulphate proteoglycan present on neural progenitors embryonically and postnatally, modulating neuronal adhesion and axon growth (Margolis et al 1996;Mai et al 1998;Allendoerfer et al 1999). Glycolipids predominate early in embryonic development, acting as regulators of cell adhesion, signal transduction and homophilic binding partners, and as agonists for receptors (van Echten-Deckert & Herget, 2006;Furukawa et al 2006;Ojima et al 2015).…”

Section: Introductionmentioning

confidence: 99%

The distribution of the proteoglycan FORSE‐1 in the developing mouse central nervous system

et al. 2018

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Glycosylation is a major post‐translational modification in which a carbohydrate known as a glycan is enzymatically attached to target proteins which regulate protein folding and stability. Glycans are strongly expressed in the developing nervous system where they play multiple roles during development. The importance of these glycan epitopes in neural development is highlighted by a group of conditions known as congenital disorders of glycosylation which lead to psychomotor difficulties, mental retardation, lissencephaly, microencephaly and epilepsy. One of these glycan epitopes, known as Lewis X, is recognised by the FORSE‐1 antibody and is regionally expressed in the developing nervous system. In this study, we report the regional and temporal expression patterns of FORSE‐1 immunolabelling during the periods of neurogenesis, gliogenesis and axonogenesis in developing mouse nervous system. We demonstrate the localisation of FORSE‐1 on subsets of neuroepithelial cells and radial glial cells, and in compartments corresponding to axon tract formation. These spatial, temporal and regional expression patterns are suggestive of roles in the determination of different cell lineages and in the patterning of white matter during development, and help provide insights into the neuroanatomical regions affected by congenital disorders of glycosylation.

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Glycolipid dynamics in generation and differentiation of induced pluripotent stem cells

Cited by 22 publications

References 29 publications

Glycosphingolipid metabolic reprogramming drives neural differentiation

Glycosphingolipid metabolic reprogramming drives neural differentiation

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

The distribution of the proteoglycan FORSE‐1 in the developing mouse central nervous system

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