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Ion Channels in Human Pluripotent Stem Cells and Their Neural Derivatives
Published in Tian-Le Xu, Long-Jun Wu, Nonclassical Ion Channels in the Nervous System, 2021
Ritika Raghavan, Robert Juniewicz, Maharaib Syed, Michael Lin, Peng Jiang
Human PSCs have been efficiently differentiated into astrocytes and oligodendrocyte progenitor cells (OPCs). Astrocytes derived from hESCs were shown to be heterogenous when compared to astrocytes differentiated from hESC-derived subpopulations of different NPCs. A previous study showed that astrocytes differentiated from both Olig2-expressing (Olig2+) and Olig2-negative (Olig2-) NPCs exhibited KV-mediated currents. Interestingly, Olig2+ NPC-derived astrocytes, but not Olig2− NPC-derived astrocytes showed Tetrodotoxin (TTX)-sensitive NaV-mediated currents (63). A subpopulation of OPCs derived from hESC cells were shown to express KV-mediated currents and large NaV-mediated currents, which enable them to fire APs (64). Studies in a mouse ESC differentiation model demonstrated that the expression of NaV in OPCs might promote their maturation to oligodendrocytes and the formation myelin (63).
Neurodevelopmental Considerations in the Patient With Necrotizing Enterocolitis
Published in David J. Hackam, Necrotizing Enterocolitis, 2021
Panagiotis Kratimenos, Frances J. Northington
Using a mouse model of NEC, Biouss et al. showed significant neuropathologic changes in the brain specimens from the NEC group, involving neuronal (CC3+, NeuN), OLs (Olig2+), and neural progenitor cell (Sox2) counts in the cortex, basal ganglia, and hippocampus compared with the breastfed control mice (14). The brain-to-body ratio was greater in mice with NEC compared to controls, which may be due to a combination of cerebral edema and undernutrition in the NEC group (14). Concentrations of markers (BiP, CHOP) of stress to the endoplasmic reticulum (ER) and markers of inflammation and microglia activation (IL6, TNFα, IBa1, GFAP) in the diseased bowel and the brain correlated with NEC in these mice. Astrocyte density in the hippocampus was increased in the NEC group. The authors also reported that the severity of intestinal injury in the ileum correlated with the severity of brain injury. Mice with NEC showed decreased thickness of the cortex, likely due to neuronal cell loss through apoptosis or necrosis, as well as hypomyelination of the subcortical white matter and hippocampus (14).
Diffuse Intrinsic Pontine Glioma
Published in David A. Walker, Giorgio Perilongo, Roger E. Taylor, Ian F. Pollack, Brain and Spinal Tumors of Childhood, 2020
Katherine E. Warren, Carolyn R. Freeman, Dannis G. van Vuurden
Because the diagnosis of DIPG has historically been determined based upon characteristic radiographic findings in the face of a typical clinical presentation, limited tissue was available for advanced pathology studies until relatively recently. DIPGs were presumed to be biologically similar to adult malignant glioma based upon similar histologic appearance at autopsy. The lack of response to any chemotherapeutic agent, including temozolomide, an alkylating agent incorporated into the standard of care for adult malignant gliomas, resulted in examination of this assumption, and intensive efforts to better characterize DIPG were initiated. The initial studies involved broader immunohistochemical characterization, which demonstrated that the majority of DIPGs are positive for GFAP, p16, p53, and EGFR, and most express stem cell markers, including OLIG2 and SOX2.15
Overview and recent advances in the targeting of medulloblastoma cancer stem cells
Published in Expert Review of Anticancer Therapy, 2021
Compelling questions remain unanswered regarding the relationship between cell-of-origin and CSCs. In one example, Zhang et al. utilized scRNA-seq to investigate the developmental hierarchy of cells within a Ptch-mutant SHH medulloblastoma mouse model, finding an OLIG2+ lineage cell as a candidate tumor initiating cell driving tumorigenesis and relapse [63]. OLIG2+ cells were highest in the neural stem cell-like population, correlating with Nestin and Sox2 expression, and decreased in prevalence with differentiation along the GNP lineage. OLIG2+ cells demonstrated higher sphere-forming capacity and tumorigenicity and were critical for tumor initiation in the mouse model. Also consistent with a cancer stem cell, OLIG2+ cells represented only a small population in mature tumors, and were enriched after chemotherapy and in relapsed tumors. Deletion of OLIG2 led to tumor growth inhibition. High OLIG2 expression was also associated with inferior outcomes in SHH medulloblastomas, though not in the other medulloblastoma subgroups.
Contribution of Human Trophoblast Progenitor Cells to Neurogenesis in Rat Focal Cerebral Ischemia Model
Published in Brain Injury, 2021
Kerem Yanar, Muge Molbay, Eylem Özaydın-Goksu, Gozde Unek, Emre Cetindağ, Ali Unal, Emin Turkay Korgun
Olig1 and Olig2 are transcription factors that induce the proliferation of progenitor cells and contribute to neuronal development. Our results show that Olig1 levels were the same in SHAM and ischemic groups, but hTPC treatment greatly increased Olig1 levels in motor neurons. Whereas Olig2 levels are similar to Olig1 levels in SHAM and ischemic groups, its levels are greatly increased in neuroglial cells after hTPC treatment (Figure 12, Figure 13).
Prognostic value of stem cell markers in glioblastoma
Published in Biomarkers, 2019
Francesc Alameda, José María Velarde, Cristina Carrato, Noemí Vidal, Montserrat Arumí, Dolores Naranjo, Maria Martinez-Garcia, Teresa Ribalta, Carme Balañá
Olig2 defines oligodendroglial differentiation and plays a role in maintaining replication in early periods of development (Gaber and Novitch 2011). In the present series, Olig2 was not expressed in 6.7% of the cases, while it was expressed in less than 10% of the tumour cells in 30.9% of the cases. The levels of Olig2 IE that we observed are similar to those reported in the literature (Popova et al. 2014).