Evaluation of BCAS1-positive immature oligodendrocytes after cerebral ischemic stroke and SVD

Jiang, Guanhua; Ayaki, Takashi; Maki, Takakuni; Yasuda, Ken; Yoshii, Daisuke; Kaji, Shunsuke; Takahashi, Ryōsuke

doi:10.1016/j.neulet.2023.137405

Cited by 4 publications

(1 citation statement)

References 52 publications

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“…Previous studies have demonstrated that BCAS1 [46] and MAG (myelin associated glycoprotein) [47] are linked with the development mechanisms of schizophrenia. Levels of BCAS1 [48], MAG (myelin associated glycoprotein) [49], ZNF208 [50] and PEG3 [51] are increased in patients with stroke. MAG (myelin associated glycoprotein) [52] participate in pathogenic processes of Parkinson’s disease.…”

Section: Discussionmentioning

confidence: 99%

Identification of key genes and signaling pathway in the pathogenesis of Huntington's disease via bioinformatics and next generation sequencing data analysis

Vastrad,

Vastrad

2024

Preprint

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Huntington's disease (HD) is the primary cause of progressive motor deficits, psychiatric symptoms, and cognitive impairment. The exact molecular mechanisms of HD pathogenesis are largely unknown. This investigation aims to identify the hub genes, miRNA and TFs in HD and explore their potential molecular regulatory network. Next generation sequencing (NGS) dataset (GSE105041) was extracted from the Gene Expression Omnibus (GEO) database. An integrated bioinformatics pipeline including identification of differentially expressed genes (DEGs), Gene ontology and REACTOME pathway enrichment analysis, protein-protein interaction (PPI) network and module analysis, miRNA-hub gene regulatory network analysis and TF-hub gene regulatory network analysis, and receiver operating characteristic curve (ROC) analysis were applied to identify hub genes, miRNA and TFs, and key drivers of HD pathogenesis. We identified 958 DEGs in the discovery phase, consisting of 479 up regulated genes and 479 down regulated genes. GO and REACTOME enrichment analyses of the 479 up regulated genes and 479 down regulated genes showed that they were mainly involved in multicellular organismal process, developmental process, signaling by GPCR and MHC class II antigen presentation. Further analysis of the PPI network using Cytoscape and PEWCC plugins identified 10 hub genes, including LRRK2, MTUS2, HOXA1, IL7R, ERBB3, EGFR, TEX101, WDR76, NEDD4L and COMT. Possible target miRNAs and TFs, including hsa-mir-1292-5p, hsa-mir-4521, ESRRB and SREBF1, were predicted by constructing a miRNA-hub gene regulatory network analysis and TF-hub gene regulatory network. This investigation used bioinformatics methods to explore the molecular pathogenesis of HD, and identified potential molecular markers. These molecular markers might provide novel ideas and methods for the early diagnosis, treatment, and monitoring of HD.

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Section: Discussionmentioning

confidence: 99%

Identification of key genes and signaling pathway in the pathogenesis of Huntington's disease via bioinformatics and next generation sequencing data analysis

Vastrad,

Vastrad

2024

Preprint

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Characterisation of GPR17‐expressing oligodendrocyte precursors in human ischaemic lesions and correlation with reactive glial responses

Raffaele,

Clausen,

Mannella

et al. 2024

The Journal of Pathology

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White matter damage and subsequent demyelination significantly contribute to long‐term functional impairment after ischaemic stroke. Identifying novel pharmacological targets to restore myelin integrity by promoting the maturation of oligodendrocyte precursor cells (OPCs) into new myelinating oligodendrocytes may open new perspectives for ischaemic stroke treatment. In this respect, previous studies highlighted the role of the G protein‐coupled membrane receptor 17 (GPR17) as a key regulator of OPC differentiation in experimental models of brain injury, including ischaemic stroke. To determine the translational value of GPR17 as a possible target in the context of human disease, we exploited immunohistochemistry to characterise the distribution of GPR17‐expressing cells in brain tissue samples from ischaemic stroke cases and correlated it with the reactive state of neighbouring glial cells. The results showed that GPR17 specifically decorates a subpopulation of differentiation‐committed OPCs, labelled by the peculiar marker breast carcinoma‐amplified sequence 1 (BCAS1), that accumulates in the peri‐infarct region in the later stages after the ischaemic event. Interestingly, the response of GPR17‐expressing cells appears to be paralleled by the switch of reactive microglia/macrophages from a phagocytic to a dystrophic phenotype and by astrocytic scar formation. A negative correlation was found between GPR17‐expressing OPCs and reactive microglia/macrophages and astrocytes surrounding chronic ischaemic lesions in female subjects, while the same relationship was less pronounced in males. These results were reinforced by bioinformatic analysis of a publicly available transcriptomic dataset, which implicated a possible role of inflammation and defective neuron‐to‐OPC communication in remyelination failure after ischaemic damage. Hence, these data strengthen the relevance of GPR17‐based remyelinating therapies for the treatment of ischaemic stroke. © 2024 The Author(s). The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.

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The dynamics of oligodendrocyte populations following permanent ischemia promotes long-term spontaneous remyelination of damaged area

Martín-Lopez,

Mallavibarrena,

Villa-Gonzalez

et al. 2024

Biochimica et Biophysica Acta (BBA) - Molecular Basis of Diseas

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Evaluation of BCAS1-positive immature oligodendrocytes after cerebral ischemic stroke and SVD

Cited by 4 publications

References 52 publications

Identification of key genes and signaling pathway in the pathogenesis of Huntington's disease via bioinformatics and next generation sequencing data analysis

Identification of key genes and signaling pathway in the pathogenesis of Huntington's disease via bioinformatics and next generation sequencing data analysis

Characterisation of GPR17‐expressing oligodendrocyte precursors in human ischaemic lesions and correlation with reactive glial responses

The dynamics of oligodendrocyte populations following permanent ischemia promotes long-term spontaneous remyelination of damaged area

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