Roles of gangliosides in the differentiation of mouse pluripotent stem cells to neural stem cells and neural cells

Ryu, Jae‐Sung; Ko, Kinarm; Ko, Kisung; Kim, Ji-su; Kim, Sun‐Uk; Chang, Kyu‐Tae; Choo, Young‐Kug

doi:10.3892/mmr.2017.6719

Cited by 16 publications

(7 citation statements)

References 75 publications

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“…Gangliosides are very important in the development (3), differentiation (4,5) and proliferation (6) of cells. Ganglioside D3 (GD3) and ganglioside D2 (GD2) are strongly expressed in neuroectoderm-derived cancers and thought to be important in the malignant transformation of tumor cells (7).…”

Section: Introductionmentioning

confidence: 99%

Epigenetic hypomethylation and upregulation of GD3s in triple negative breast cancer

et al. 2019

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Background: Breast cancer remains a major health problem in the world. Triple-negative breast cancer (TNBC) is an aggressive subtype with very poor prognosis. Up to now, the mechanism behind TNBC's activity is still unclear and no candidate drug target has been identified. Thus, it is of critical importance to elucidate the pathways in TNBC and identify the relevant biomarkers. Recent studies showed that ganglioside D3 synthase (GD3s) played a very important role in development of cancers. However, the physiological functions and associated pathways of GD3s in TNBC are still unclear.Methods: In silico analysis of the expression of GD3s in TNBC was conducted using The Cancer Genome Atlas (TCGA) and Oncomine databases. The proliferation of breast cancer cells was measured by MTT assay, colony formation by the soft agar method, and migration and invasion using Boyden chamber inserts.The methylation level of the gene encoding GD3s, ST8SIA1, in specimens was assessed by qMS-PCR and in silico using the UCSC gene browser. Protein expression was examined via immunohistochemistry (IHC), qRT-PCR and Western immunoblotting.Results: In silico analysis showed a higher GD3s expression in ER − than ER + breast cancers and GD3s was also highly expressed in TNBC compared to other types of breast cancers. The elevated GD3s expression in TNBC cells and tissues was associated with hypomethylation of the ST8SIA1 gene. Overexpression of GD3s in human breast cancer cells increased their proliferation, migration, invasion and colony formation ability. GD3s expression in breast cancers was closely associated with relapse-free survival (RFS) and overall survival (OS).Conclusions: In summary, these results suggest that GD3s may be a potential biomarker and drug target in treatment of TNBC.

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Section: Introductionmentioning

confidence: 99%

Epigenetic hypomethylation and upregulation of GD3s in triple negative breast cancer

et al. 2019

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“…GD3 was the most abundant ganglioside in the COs (Figure S11), and the levels of GD3 and GM3 remained steady at all time points, indicating high NSC reserve even at a late stage of CO proliferation, an analogy with mature brain tissue . GD3 interacts with the epidermal growth factor receptor (EGFR) and induces neural precursor cell differentiation and neurite formation . We observed a progressive increase in complex neuronal gangliosides from D48 until D110, followed by a decline in D135 and D160 (Figures c and S11).…”

Section: Resultsmentioning

confidence: 94%

Single Cerebral Organoid Mass Spectrometry of Cell-Specific Protein and Glycosphingolipid Traits

et al. 2023

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Cerebral organoids are a prolific research topic and an emerging model system for neurological diseases in human neurobiology. However, the batch-to-batch reproducibility of current cultivation protocols is challenging and thus requires a high-throughput methodology to comprehensively characterize cerebral organoid cytoarchitecture and neural development. We report a mass spectrometry-based protocol to quantify neural tissue cell markers, cell surface lipids, and housekeeping proteins in a single organoid. Profiled traits probe the development of neural stem cells, radial glial cells, neurons, and astrocytes. We assessed the cell population heterogeneity in individually profiled organoids in the early and late neurogenesis stages. Here, we present a unifying view of cell-type specificity of profiled protein and lipid traits in neural tissue. Our workflow characterizes the cytoarchitecture, differentiation stage, and batch cultivation variation on an individual cerebral organoid level.

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“…Raft component sphingolipids or cholesterol has been reported to play a role in neural function and cell proliferation and differentiation, including neural differentiation from embryonic bodies or neural progenitor cells [6][39]. Much less is known about the potential relationship of rafts with early differentiation events.…”

Section: Resultsmentioning

confidence: 99%

Lipid rafts increase to facilitate ectoderm lineage specification of differentiating embryonic stem cells

Cao

Huo

et al. 2019

Preprint

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Lipid rafts are packed nanoscopic domains on plasma membrane and essential signalling platforms for transducing extracellular stimuli into cellular responses. Although depletion of raft component glycoshpingolipids causes abnormality particularly in ectoderm layer formation, it remains unclear whether rafts play a role in lineage determination, a critical but less-known stage in lineage commitment.Here, inducing mouse embryonic stem cell (mESC) differentiation with retinoic acid (RA), we observed lipid rafts increased since early stage, especially in ectoderm-like cells. Stochastic optical reconstruction microscopy characterized at super-resolution the distinct raft features in mESCs and the derived differentiated cells. Furthermore, RA-induced commitment of ectoderm-like cells was significantly diminished not only by genetic ablation of rafts but by applying inhibitor for glycosphingolipids or cholesterol at early differentiation stages. Meanwhile, raft inhibition delayed RA-induced pluripotency exit, an early step required for differentiation. Therefore, lipid rafts increase and facilitate ectoderm lineage specification as well as pluripotency exit during mESC differentiation.

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Roles of gangliosides in the differentiation of mouse pluripotent stem cells to neural stem cells and neural cells

Cited by 16 publications

References 75 publications

Epigenetic hypomethylation and upregulation of GD3s in triple negative breast cancer

Epigenetic hypomethylation and upregulation of GD3s in triple negative breast cancer

Single Cerebral Organoid Mass Spectrometry of Cell-Specific Protein and Glycosphingolipid Traits

Lipid rafts increase to facilitate ectoderm lineage specification of differentiating embryonic stem cells

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