BCOR Internal Tandem Duplication Expression in Neural Stem Cells Promotes Growth, Invasion, and Expression of PRC2 Targets

Central nervous system tumor with BCL6-corepressor internal tandem duplication (CNS-BCOR ITD) is a malignant entity characterized by recurrent alterations in exon 15 encoding the essential binding domain for the polycomb repressive complex (PRC). In contrast to deletion or truncating mutations seen in other tumors, BCOR expression is upregulated in CNS-BCOR ITD, and a distinct oncogenic mechanism has been suggested. However, the effects of this change on the biology of neuroepithelial cells is poorly understood. In this study, we introduced either wildtype BCOR or BCOR-ITD into human and murine neural stem cells and analyzed them with quantitative RT-PCR and RNA-sequencing, as well as growth, clonogenicity, and invasion assays. In human cells, BCOR-ITD promoted derepression of PRC2-target genes compared to wildtype BCOR. A similar effect was found in clinical specimens from previous studies. However, no growth advantage was seen in the human neural stem cells expressing BCOR-ITD, and long-term models could not be established. In the murine cells, both wildtype BCOR and BCOR-ITD overexpression affected cellular differentiation and histone methylation, but only BCOR-ITD increased cellular growth, invasion, and migration. BCOR-ITD overexpression drives transcriptional changes, possibly due to altered PRC function, and contributes to the oncogenic transformation of neural precursors.

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TIMP-1 modulates chemotaxis of human neural stem cells through CD63 and integrin signalling

Biochemical Journal ◽

10.1042/bj20131119 ◽

2014 ◽

Vol 459 (3) ◽

pp. 565-576 ◽

Cited By ~ 26

Author(s):

Soo Youn Lee ◽

Jung Mi Kim ◽

Soo Young Cho ◽

Hyun Suk Kim ◽

Hee Sun Shin ◽

...

Keyword(s):

Stem Cells ◽

Plasma Membrane ◽

Cell Adhesion ◽

Neural Stem Cells ◽

Brain Tumour ◽

Β1 Integrin ◽

Human Neural Stem Cells ◽

Cell Adhesion And Migration ◽

And Migration

Human neural stem cells possess an inherent brain tumour tropism. We identified brain tumour-derived TIMP-1 as a novel chemoattractant for human neural stem cells. TIMP-1 binding to CD63 at the plasma membrane activated β1 integrin-mediated signalling, inducing cell adhesion and migration.

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Neutrophils Induce Astroglial Differentiation and Migration of Human Neural Stem Cells via C1q and C3a Synthesis

The Journal of Immunology ◽

10.4049/jimmunol.1600064 ◽

2017 ◽

Vol 199 (3) ◽

pp. 1069-1085 ◽

Cited By ~ 10

Author(s):

Mitra J. Hooshmand ◽

Hal X. Nguyen ◽

Katja M. Piltti ◽

Francisca Benavente ◽

Samuel Hong ◽

...

Keyword(s):

Stem Cells ◽

Neural Stem Cells ◽

Human Neural Stem Cells ◽

And Migration

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Aberrant Expression of Circulating MicroRNA Leads to the Dysregulation of Alpha-Synuclein and Other Pathogenic Genes in Parkinson’s Disease

Frontiers in Cell and Developmental Biology ◽

10.3389/fcell.2021.695007 ◽

2021 ◽

Vol 9 ◽

Author(s):

Meng Cai ◽

Songshan Chai ◽

Tao Xiong ◽

Jun Wei ◽

Weibing Mao ◽

...

Keyword(s):

Parkinson’S Disease ◽

Stem Cells ◽

Parkinson's Disease ◽

Protein Kinase ◽

Neural Stem Cells ◽

Regulatory Network ◽

Target Genes ◽

Alpha Synuclein ◽

Related Gene ◽

Human Neural Stem Cells

A group of circulating microRNAs (miRNAs) have been implicated in the pathogenesis of Parkinson’s disease. However, a comprehensive study of the interactions between pathogenic miRNAs and their downstream Parkinson’s disease (PD)-related target genes has not been performed. Here, we identified the miRNA expression profiles in the plasma and circulating exosomes of Parkinson’s disease patients using next-generation RNA sequencing. Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) analyses showed that the miRNA target genes were enriched in axon guidance, neurotrophin signaling, cellular senescence, and the Transforming growth factor-β (TGF-β), mitogen-activated protein kinase (MAPK), phosphatidylinositol 3-kinase (PI3K)-protein kinase B (AKT) and mechanistic target of rapamycin (mTOR) signaling pathways. Furthermore, a group of aberrantly expressed miRNAs were selected and further validated in individual patient plasma, human neural stem cells (NSCs) and a rat model of PD. More importantly, the full scope of the regulatory network between these miRNAs and their PD-related gene targets in human neural stem cells was examined, and the findings revealed a similar but still varied downstream regulatory cascade involving many known PD-associated genes. Additionally, miR-23b-3p was identified as a novel direct regulator of alpha-synuclein, which is possibly the key component in PD. Our current study, for the first time, provides a glimpse into the regulatory network of pathogenic miRNAs and their PD-related gene targets in PD. Moreover, these PD-associated miRNAs may serve as biomarkers and novel therapeutic targets for PD.

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Indonesian Ginger (Bangle) Extract Promotes Neurogenesis of Human Neural Stem Cells through WNT Pathway Activation

International Journal of Molecular Sciences ◽

10.3390/ijms21134772 ◽

2020 ◽

Vol 21 (13) ◽

pp. 4772

Author(s):

Kazumi Hirano ◽

Miwa Kubo ◽

Yoshiyasu Fukuyama ◽

Masakazu Namihira

Keyword(s):

Stem Cells ◽

Neural Stem Cells ◽

Cortical Neurons ◽

Wnt Pathway ◽

Target Genes ◽

Human Neural Stem Cells ◽

Pathway Activation ◽

Underlying Mechanisms ◽

Canonical Wnt

Indonesian ginger (Zingiber purpureum Rosc.), also known as Bangle, exhibits neurotrophic effects on cultured murine cortical neurons and in the adult mouse brain, but the underlying mechanisms remain unknown. Here, using human fetal neural stem cells (hfNSCs) as a model system for in vitro human neurogenesis, we show that Bangle extracts activate canonical WNT/β-catenin signaling. Bangle extract-treatment of hfNSCs not only promoted neuronal differentiation, but also accelerated neurite outgrowth from immature neurons. Furthermore, Bangle extracts induced expression of neurogenic genes and WNT signaling-target genes, and facilitated the accumulation of β-catenin in nuclei of hfNSC. Interestingly, altered histone modifications were also observed in Bangle-treated hfNSCs. Together, these findings demonstrate that Bangle contributes to hfNSC neurogenesis by WNT pathway and epigenetic regulation.

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mRNA-Driven Generation of Transgene-Free Neural Stem Cells from Human Urine-Derived Cells

Cells ◽

10.3390/cells8091043 ◽

2019 ◽

Vol 8 (9) ◽

pp. 1043 ◽

Cited By ~ 1

Author(s):

Phil Jun Kang ◽

Daryeon Son ◽

Tae Hee Ko ◽

Wonjun Hong ◽

Wonjin Yun ◽

...

Keyword(s):

Stem Cells ◽

Neural Stem Cells ◽

Human Urine ◽

Neurological Disorders ◽

Therapeutic Potential ◽

Embryonic Stem ◽

Global Gene Expression ◽

Patient Specific ◽

Human Neural Stem Cells

Human neural stem cells (NSCs) hold enormous promise for neurological disorders, typically requiring their expandable and differentiable properties for regeneration of damaged neural tissues. Despite the therapeutic potential of induced NSCs (iNSCs), a major challenge for clinical feasibility is the presence of integrated transgenes in the host genome, contributing to the risk for undesired genotoxicity and tumorigenesis. Here, we describe the advanced transgene-free generation of iNSCs from human urine-derived cells (HUCs) by combining a cocktail of defined small molecules with self-replicable mRNA delivery. The established iNSCs were completely transgene-free in their cytosol and genome and further resembled human embryonic stem cell-derived NSCs in the morphology, biological characteristics, global gene expression, and potential to differentiate into functional neurons, astrocytes, and oligodendrocytes. Moreover, iNSC colonies were observed within eight days under optimized conditions, and no teratomas formed in vivo, implying the absence of pluripotent cells. This study proposes an approach to generate transplantable iNSCs that can be broadly applied for neurological disorders in a safe, efficient, and patient-specific manner.

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Vertical Nanowire Electrode Array for Enhanced Neurogenesis of Human Neural Stem Cells via Intracellular Electrical Stimulation

Nano Letters ◽

10.1021/acs.nanolett.0c04635 ◽

2021 ◽

Author(s):

Juyoung Kwon ◽

Jong Seung Lee ◽

Jaejun Lee ◽

Jukwan Na ◽

Jaesuk Sung ◽

...

Keyword(s):

Stem Cells ◽

Electrical Stimulation ◽

Neural Stem Cells ◽

Electrode Array ◽

Human Neural Stem Cells

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A Tool for Accurate Stoichiometric Composition of Cryopreservative Media for Fetal and Induced Pluripotent Stem Cell‐Derived Human Neural Stem Cells

Current Protocols ◽

10.1002/cpz1.123 ◽

2021 ◽

Vol 1 (5) ◽

Author(s):

Walter D. Niles ◽

Evan Y. Snyder

Keyword(s):

Stem Cells ◽

Stem Cell ◽

Neural Stem Cells ◽

Pluripotent Stem Cell ◽

Stoichiometric Composition ◽

Induced Pluripotent Stem Cell ◽

Human Neural Stem Cells ◽

Induced Pluripotent

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miR-373-3p Regulates Invasion and Migration Abilities of Trophoblast Cells via Targeted CD44 and Radixin

International Journal of Molecular Sciences ◽

10.3390/ijms22126260 ◽

2021 ◽

Vol 22 (12) ◽

pp. 6260

Author(s):

Hyun-Jung Lee ◽

Seung Mook Lim ◽

Hee Yeon Jang ◽

Young Ran Kim ◽

Joon-Seok Hong ◽

...

Keyword(s):

Preterm Labor ◽

Target Genes ◽

Gene Array ◽

Migration And Invasion ◽

Trophoblast Cells ◽

Invasion And Migration ◽

Mirna Array ◽

Qrt Pcr ◽

Putative Target ◽

And Migration

Preterm labor (PTL) is one of the obstetric complications, and is known to be associated with abnormal maternal inflammatory response and intrauterine inflammation and/or infection. However, the expression of specific miRNAs associated with PTL is not clear. In this study, we performed combination analysis of miRNA array and gene array, and then selected one miRNA (miR-373-3p) and its putative target genes (CD44 and RDX) that exhibited large expression differences in term and PTL placentas with or without inflammation. Using qRT-PCR and luciferase assays, we confirmed that miR-373-3p directly targeted CD44 and RDX. Overexpression of miR-373-3p reduced the migration and invasion of trophoblast cells, while inhibition of miR-373-3p restored the migration and invasion abilities of trophoblast cells. Finally, we validated the expression of miR-373-3p and its target genes in clinical patients’ blood. miR-373-3p was increased in PTL patients’ blood, and was the most expressed in PTL patients’ blood with inflammation. In addition, by targeting the miR-373-3p, CD44 and RDX was decreased in PTL patients’ blood, and their expression were the lowest in PTL patients’ blood with inflammation. Taken together, these findings suggest that miR-373-3p and its target genes can be potential biomarkers for diagnosis of PTL.

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