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Ependymoma in Childhood and Adolescence
Published in David A. Walker, Giorgio Perilongo, Roger E. Taylor, Ian F. Pollack, Brain and Spinal Tumors of Childhood, 2020
It has been postulated that embryonic neural stem cells (NSCs) arising from different parts of the CNS are transformed by different gene mutations, thereby giving rise to biologically distinct types of ependymoma. For example, RELA gene fusions are common in supratentorial ependymomas, but virtually absent in fourth-ventricle tumors.17 Radial glia-like cancer stem cells have been proposed as the candidate cell of origin for supratentorial and spinal ependymomas.67 Cancer stem cells expressing the radial glial cell immunophenotype CD133+/Nestin+/RC2+/BLBP+ were able to recapitulate supratentorial ependymoma when orthotopically transplanted into immunocompromised mice.67 This theory was supported by work in transgenic mice with demonstration of regional, developmental, and genetic differences between NSCs taken from different brain locations at different stages of development. For example, EPHB2, a putative oncogene for supratentorial ependymoma, transformed forebrain NSCs to generate supratentorial ependymomas in mice, but not spinal or hindbrain disease.68
Nervous System
Published in Pritam S. Sahota, James A. Popp, Jerry F. Hardisty, Chirukandath Gopinath, Page R. Bouchard, Toxicologic Pathology, 2018
Mark T. Butt, Alys Bradley, Robert Sills
The staining characteristics and anaplastic appearance of some tumors diagnosed as or resembling classic astrocytomas have been postulated to be due to a radial glial cell origin and/or phenotype (Giordana 1992). Rodent radial glial cells do not express GFAP (McDermott 2005). Reinduction of ErbB2 in adult astrocytes results in regaining radial glial cell identity and enhanced proliferation of these dedifferentiated cells (Ghashghaei et al. 2007).
Paediatric oncology
Published in Pat Price, Karol Sikora, Treatment of Cancer, 2014
Stephen Lowis, Rachel Cox, John Moppett, Antony Ng
Patterns of gene expression have been identified that separate supratentorial, posterior fossa and spinal ependymoma into clearly distinct entities. Using array comparative genome hybridization, three subgroups of posterior fossa ependymoma have been identified, which are otherwise not distinguishable by conventional means. Supratentorial tumours, for example, express NOTCH and EPHB-EPHRIN pathways, whereas spinal ependymomas express members of the Homeobox (HOX) family. A putative stem cell of ependymomas, the radial glial cell, has been identified on morphological grounds and on the basis of region-specific gene expression.408,437
GAP junctions: multifaceted regulators of neuronal differentiation
Published in Tissue Barriers, 2022
Sarmistha Talukdar, Luni Emdad, Swadesh K. Das, Paul B. Fisher
Radial glial coupling and HC activity are also important during neurogenesis. Radial glial cell GJ coupling is observed to be highest during mid-neurogenesis, which later decreases during late neurogenesis.114,161 The HCs present on S phase radial glia initiate waves of Ca2+ signaling by releasing ATP, which then binds to P2Y1 receptors on the adjacent cells causing an IP3-mediated release of Ca2+ during late neurogenesis stages.114,162 Moreover, expression of the GJ proteins Cx26 and Cx43 levels are observed to be at their peak during M phase and S phase, respectively.114,163 The importance of coupling is implied by pharmacological studies where blocking coupling or Ca2+ waves was observed to inhibit entry of the cells into the S phase of the cell cycle.114,161,162 After radial glia divide asymmetrically, the newly formed neurons need to migrate to the appropriate lamina of the cortical plate.114 Radial glial cells also assist in this process of guiding the new neurons to their destination apart from being the stem cells of the developing cortex. The newly formed neurons migrate in very close association with radial glial fibers114,159,164,165 (Figure 7) and GJs possibly facilitate communication between the radial fibers and the migrating neurons.17,114,166–168
Further understanding of glioma mechanisms of pathogenesis: implications for therapeutic development
Published in Expert Review of Anticancer Therapy, 2020
Michael Ruff, Sani Kizilbash, Jan Buckner
Recently, it has been demonstrated that 1p-19q co-deleted gliomas have a decreased ability to produce ultra-long membrane protrusions, termed tumor-associated microtubules (TMs), which appear to be a mechanism of tumor resilience and pathogenesis [50]. TMs enable their host cells to interconnect and form a functional resistance network with tumor microtubules, conveying resistance to surgical lesions, chemotherapy, and radiotherapy [1]. Cells that harbor TMs demonstrate the ability to engage a pathologic healing response with cell densities that significantly exceed those of non-lesioned brain regions over time when compared to adjacent non-lesioned areas [1]. TMs serve as routes for brain invasion, proliferation, and a means for inter-connection over long distances within the host. TMs are highly dynamic structures, similar to the neuronal growth cone present in radial glial-cell processes seen during brain development. Of absolute relevance, those cells within astrocytoma models connected by these TMs appear to be protected within the network from chemotherapy and radiotherapy compared to astrocytoma cells not sufficiently connected by TMs. Unconnected tumor cells are much more susceptible to therapy in mouse models. The mechanisms by which these inter-connected TMs resist therapy include the ability to buffer calcium in the setting of radiotherapy and the ability to re-supply damaged cells and organelles such as mitochondria and even nuclei via TMs [1]. These tumor microtubules are able to act as a functional syncytium. This interconnectedness appears to be inversely related with 1p/19q co-deletion. 1p/19q co-deleted cells have reduced expression of GAP43, which is a driver or neuronal growth-cone formation [1].
Neuromodulatory effects of SARS-CoV2 infection: Possible therapeutic targets
Published in Expert Opinion on Therapeutic Targets, 2021
Sonali Kumar, Ozasvi R Shanker, Neeraj Kumari, Manjari Tripathi, P Sarat Chandra, Aparna Banerjee Dixit, Jyotirmoy Banerjee
Interestingly, a recent study has shown that SARS-CoV-2 can also infect and replicate in neurospheres and brain organoids originating from induced pluripotent stem cells (iPSCs). The organoids were positively stained for neuronal markers, such as TUJ1 (a marker for neuronal cells), PAX6 (radial glial cell marker), and Nestin (proliferating neural progenitor cell marker). Moreover, the authors confirmed the presence of ACE2 receptors, TMPRSS2, FURIN, and Cathepsin L in brain cells which are required for infection with SARS-CoV-2 [51]. This further widens the knowledge of the available routes for viral entry.