scholarly journals Ddx20, an Olig2 binding factor, governs the survival of neural and oligodendrocyte progenitor cells via proper Mdm2 splicing and p53 suppression

2022 ◽  
Author(s):  
Norihisa Bizen ◽  
Asim K. Bepari ◽  
Li Zhou ◽  
Manabu Abe ◽  
Kenji Sakimura ◽  
...  
Keyword(s):  
Nervous System ◽  
Progenitor Cells ◽  
Neural Progenitor Cells ◽  
Cell Types ◽  
Protein Stabilization ◽  
Conditional Knockout ◽  
Oligodendrocyte Progenitor Cells ◽  
Oligodendrocyte Progenitor ◽  
Dead Box ◽  
Smn Complex

AbstractOlig2 is indispensable for motoneuron and oligodendrocyte fate-specification in the pMN domain of embryonic spinal cords, and also involved in the proliferation and differentiation of several cell types in the nervous system, including neural progenitor cells (NPCs) and oligodendrocytes. However, how Olig2 controls these diverse biological processes remains unclear. Here, we demonstrated that a novel Olig2-binding protein, DEAD-box helicase 20 (Ddx20), is indispensable for the survival of NPCs and oligodendrocyte progenitor cells (OPCs). A central nervous system (CNS)-specific Ddx20 conditional knockout (cKO) demonstrated apoptosis and cell cycle arrest in NPCs and OPCs, through the potentiation of the p53 pathway in DNA damage-dependent and independent manners, including SMN complex disruption and the abnormal splicing of Mdm2 mRNA. Analyzes of Olig2 null NPCs showed that Olig2 contributed to NPC proliferation through Ddx20 protein stabilization. Our findings provide novel mechanisms underlying the Olig2-mediated proliferation of NPCs, via the Ddx20-p53 axis, in the embryonic CNS.

Microglial Activation Induces Generation of Oligodendrocyte Progenitor Cells from the Subventricular Zone after Focal Demyelination in the Corpus Callosum

2018 ◽  
Vol 40 (1) ◽  
pp. 54-63 ◽  
Author(s):  
Masae Naruse ◽  
Koji Shibasaki ◽  
Hiroya Shimauchi-Ohtaki ◽  
Yasuki Ishizaki
Keyword(s):  
Corpus Callosum ◽  
Progenitor Cells ◽  
Subventricular Zone ◽  
Microglial Activation ◽  
Neural Progenitor Cells ◽  
Internal Capsule ◽  
Oligodendrocyte Progenitor Cells ◽  
Oligodendrocyte Progenitor ◽  
Demyelinating Lesions ◽  
Focal Demyelination

Neuroblasts derived from neural stem cells (NSCs) in the subventricular zone (SVZ) migrate along the rostral migratory stream into the olfactory bulb to generate interneurons under normal physiological conditions. When demyelination occurs, NSCs or neural progenitor cells (NPCs) in the SVZ provide newly formed oligodendrocytes to demyelinated lesions. The plasticity of NSC/NPC lineages may tend to oligodendrogenesis under the influence of demyelinated lesions. The mechanisms, however, still remain unknown. This study revealed that focal demyelination in the corpus callosum caused activation of the microglia, not only at the site of demyelination but also in the SVZ, and dramatically increased the generation of oligodendrocyte progenitor cells (OPCs) in the SVZ. Furthermore, the inhibition of microglial activation by minocycline treatment decreased OPC generation in the SVZ, suggesting that microglial activation in the SVZ, induced by the focal demyelination in the corpus callosum, regulates NSC/NPC lineage plasticity in situ. In contrast to the findings regarding demyelination in the corpus callosum, inducing focal demyelination in the internal capsule did not induce either microglial activation or OPC generation in the SVZ. These results suggest that the mechanism of OPC generation in the SVZ after inducing demyelinating lesions could be different across the demyelinated regions.

scholarly journals mTORC2 loss in oligodendrocyte progenitor cells results in regional hypomyelination in the central nervous system

2022 ◽  
Author(s):  
Kristin D Dahl ◽  
Hannah A Hathaway ◽  
Adam R Almeida ◽  
Jennifer Bourne ◽  
Tanya L Brown ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Central Nervous System ◽  
Nervous System ◽  
Corpus Callosum ◽  
Signaling Pathways ◽  
Progenitor Cells ◽  
Myelin Proteins ◽  
Oligodendrocyte Progenitor Cells ◽  
Oligodendrocyte Progenitor ◽  
The Central Nervous System

In the central nervous system (CNS), oligodendrocyte progenitor cells (OPCs) differentiate into mature oligodendrocytes to generate myelin, which is essential for normal nervous system function. OPC differentiation is driven by signaling pathways such as mTOR (Mechanistic Target of Rapamycin), which functions in two distinct complexes: mTOR complex 1 (mTORC1) and mTOR complex 2 (mTORC2), containing Raptor or Rictor respectively. In the current studies, mTORC2 signaling was selectively deleted from OPCs in PDGFRα-Cre X Rictorfl/fl mice. This study examined developmental myelination in male and female mice, comparing the impact of mTORC2 deletion in the corpus callosum and spinal cord. In both corpus callosum and spinal cord, Rictor loss in OPCs resulted in early reduction in myelin RNAs and some myelin proteins. However, these deficits rapidly recovered in spinal cord, where normal myelin abundance and thickness was noted at post-natal day 21 and 1.5 months. By contrast, the losses in corpus callosum resulted in severe hypomyelination, and increased unmyelinated axons. The current studies focus on uniquely altered signaling pathways following mTORC2 loss in developing oligodendrocytes. A major mTORC2 substrate is phospho-Akt-S473, which was significantly reduced throughout development in both corpus callosum and spinal cord at all ages measured, yet this had little impact in spinal cord. Loss of mTORC2 signaling resulted in decreased expression of actin regulators such as gelsolin in corpus callosum, but only minimal loss in spinal cord. The current study establishes a regionally-specific role for mTORC2 signaling in OPCs, particularly in the corpus callosum.

A Novel Injectable Chitosan Sponge Containing Brain Derived Neurotrophic Factor (BDNF) to Enhance Human Oligodendrocyte Progenitor Cells' (OPC) Differentiation

2014 ◽  
Vol 1621 ◽  
pp. 127-132
Author(s):  
Mina Mekhail ◽  
Qiao-Ling Cui ◽  
Guillermina Almazan ◽  
Jack Antel ◽  
Maryam Tabrizian
Keyword(s):  
Progenitor Cells ◽  
Spinal Cord Injuries ◽  
Cell Types ◽  
Therapeutic Modality ◽  
Oligodendrocyte Progenitor Cells ◽  
High Porosity ◽  
Oligodendrocyte Progenitor ◽  
Wide Range ◽  
First Time

ABSTRACTWe developed a rapidly-gelling chitosan sponge crosslinked with Guanosine 5'-Diphosphate (GDP). GDP has not been previously explored as an anionic crosslinker, and it was used in this application since the nucleoside guanosine has been shown to improve remyelination in situ, and thus its presence in the sponge composition was hypothesized to induce Oligodendrocyte Progenitor Cells' (OPC) differentiation. In addition to the chemical composition tailored to target OPCs, the developed chitosan sponge possesses a wide range of desirable physicochemical properties such as: rapid gelation, high porosity with interconnected pores, moduli of elasticity resembling that of soft tissue and cytocompatibility with many cell types. Moreover, protein encapsulation into the sponges was possible with high encapsulation efficiencies (e.g. BMP-7 and NT-3). In this study, BDNF was encapsulated in the chitosan sponges with an encapsulation efficiency greater than 80% and a sustained release over a 16-day period was achieved. We demonstrate here for the first time, the attachment of human fetal OPCs to the sponges and their differentiation after 12 days of culture. Overall, this newly-introduced injectable sponge is a promising therapeutic modality that can be used to enhance remyelination post-spinal cord injuries.

scholarly journals Glial Patchwork: Oligodendrocyte Progenitor Cells and Astrocytes Blanket the Central Nervous System

2022 ◽  
Vol 15 ◽  
Author(s):  
Heather M. Barber ◽  
Maria F. Ali ◽  
Sarah Kucenas
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Progenitor Cells ◽  
Developmental Process ◽  
Emergent Behavior ◽  
Oligodendrocyte Progenitor Cells ◽  
Oligodendrocyte Progenitor ◽  
Cellular Behaviors ◽  
The Central Nervous System ◽  
Impact Injury

Tiling is a developmental process where cell populations become evenly distributed throughout a tissue. In this review, we discuss the developmental cellular tiling behaviors of the two major glial populations in the central nervous system (CNS)—oligodendrocyte progenitor cells (OPCs) and astrocytes. First, we discuss OPC tiling in the spinal cord, which is comprised of the three cellular behaviors of migration, proliferation, and contact-mediated repulsion (CMR). These cellular behaviors occur simultaneously during OPC development and converge to produce the emergent behavior of tiling which results in OPCs being evenly dispersed and occupying non-overlapping domains throughout the CNS. We next discuss astrocyte tiling in the cortex and hippocampus, where astrocytes migrate, proliferate, then ultimately determine their exclusive domains by gradual removal of overlap rather than sustained CMR. This results in domains that slightly overlap, allowing for both exclusive control of “synaptic islands” and astrocyte-astrocyte communication. We finally discuss the similarities and differences in the tiling behaviors of these glial populations and what remains unknown regarding glial tiling and how perturbations to this process may impact injury and disease.

scholarly journals TCTP is Essential for Cell Proliferation and Survival during CNS Development

Cells ◽  
2020 ◽  
Vol 9 (1) ◽  
pp. 133 ◽  
Author(s):  
Sung-Ho Chen ◽  
Chin-Hung Lu ◽  
Ming-Jen Tsai
Keyword(s):  
Cell Proliferation ◽  
Nervous System ◽  
Progenitor Cells ◽  
Neural Progenitor Cells ◽  
Perinatal Death ◽  
Ventricular Zone ◽  
Neuronal Loss ◽  
Conditional Knockout ◽  
Terminal Deoxynucleotidyl Transferase ◽  
Cns Development

Translationally controlled tumor-associated protein (TCTP) has been implicated in cell growth, proliferation, and apoptosis through interacting proteins. Although TCTP is expressed abundantly in the mouse brain, little is known regarding its role in the neurogenesis of the nervous system. We used Nestin-cre-driven gene-mutated mice to investigate the function of TCTP in the nervous system. The mice carrying disrupted TCTP in neuronal and glial progenitor cells died at the perinatal stage. The NestinCre/+; TCTPf/f pups displayed reduced body size at postnatal day 0.5 (P0.5) and a lack of milk in the stomach compared with littermate controls. In addition to decreased cell proliferation, terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling (TUNEL) and caspase assay revealed that apoptosis was increased in newly committed TCTP-disrupted cells as they migrated away from the ventricular zone. The mechanism may be that the phenotype from specific deletion of TCTP in neural progenitor cells is correlated with the decreased expression of cyclins D2, E2, Mcl-1, Bcl-xL, hax-1, and Octamer-binding transcription factor 4 (Oct4) in conditional knockout mice. Our results demonstrate that TCTP is a critical protein for cell survival during early neuronal and glial differentiation. Thus, enhanced neuronal loss and functional defect in Tuj1 and doublecortin-positive neurons mediated through increased apoptosis and decreased proliferation during central nervous system (CNS) development may contribute to the perinatal death of TCTP mutant mice.

scholarly journals Sera from Patients with NMOSD Reduce the Differentiation Capacity of Precursor Cells in the Central Nervous System

2021 ◽  
Vol 22 (10) ◽  
pp. 5192
Author(s):  
Ulises Gómez-Pinedo ◽  
Yolanda García-Ávila ◽  
Lucía Gallego-Villarejo ◽  
Jordi A. Matías-Guiu ◽  
María Soledad Benito-Martín ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Progenitor Cells ◽  
Neuromyelitis Optica ◽  
Subventricular Zone ◽  
Precursor Cells ◽  
Oligodendrocyte Progenitor Cells ◽  
Oligodendrocyte Progenitor ◽  
Differentiation Capacity ◽  
The Central Nervous System

Introduction: AQP4 (aquaporin-4)–immunoglobulin G (IgG)-mediated neuromyelitis optica spectrum disorder (NMOSD) is an inflammatory demyelinating disease that affects the central nervous system, particularly the spinal cord and optic nerve; remyelination capacity in neuromyelitis optica is yet to be determined, as is the role of AQP4–IgG in cell differentiation. Material and Methods: We included three groups—a group of patients with AQP4–IgG-positive neuromyelitis optica, a healthy group, and a sham group. We analyzed differentiation capacity in cultures of neurospheres from the subventricular zone of mice by adding serum at two different times: early and advanced stages of differentiation. We also analyzed differentiation into different cell lines. Results and Conclusions: The effect of sera from patients with NMOSD on precursor cells differs according to the degree of differentiation, and probably affects oligodendrocyte progenitor cells from NG2 cells to a lesser extent than cells from the subventricular zone; however, the resulting oligodendrocytes may be compromised in terms of maturation and possibly limited in their ability to generate myelin. Furthermore, these cells decrease in number with age. It is very unlikely that the use of drugs favoring the migration and differentiation of oligodendrocyte progenitor cells in multiple sclerosis would be effective in the context of neuromyelitis optica, but cell therapy with oligodendrocyte progenitor cells seems to be a potential alternative.

scholarly journals RalGAPα1is dispensable for embryonic cortical morphogenesisin mice

2021 ◽  
Author(s):  
Yingqian Xia ◽  
Chaoli Huang ◽  
Sangsang Zhu ◽  
Qiaoli Chen ◽  
Guiquan Chen ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Brain Development ◽  
Progenitor Cells ◽  
Neural Progenitor Cells ◽  
Cortical Development ◽  
Neural Progenitor ◽  
Conditional Knockout ◽  
Deletion Syndrome ◽  
The Central Nervous System

Abstract Background: Cortical morphogenesis is a complex process and involves a large number of genes. RalGAPα1 gene (also called Tulip1 ), mapped to chromosome 14q13.2, is a candidate gene for the 14q13 deletion syndrome associated with delayed brain development. However, it remains unknown whether RalGAPα1 directly regulates cortical development. Methods: To address the above question, we generated neural progenitor cells (NPCs) specific RalGAPα1 conditional knockout (cKO) mice through crossing RalGAPα1 f/f to Nestin-Cre transgenic (Tg) mice in which the Cre recombinase is expressed in neural progenitor cells and derived neurons in the central nervous system (CNS) since very early stage of development. Morphological, biochemistry and immunohistochemistry (IHC) methods were used to evaluate brain development. Results: We found that the brain size, shape and cortical laminations were comparable between control and RalGAPα1 cKO mice. Moreover, the populations and proliferations of NPCs in the ventricular and subventricular zones were not different between control and RalGAPα1 cKO cortices. Conclusions: Inactivation of RalGAPα1 in the central nervous system in murine model does not significantly affect the embryonic cortical development. Keywords: RalGAPα1 ; cortical development; neural progenitor cells; neurodevelopmental disease

Developmental trajectory of oligodendrocyte progenitor cells in the human brain revealed by single cell RNA sequencing

Glia ◽  
2020 ◽  
Vol 68 (6) ◽  
pp. 1291-1303 ◽  
Author(s):  
Kelly Perlman ◽  
Charles P. Couturier ◽  
Moein Yaqubi ◽  
Arnaud Tanti ◽  
Qiao‐Ling Cui ◽  
...  
Keyword(s):  
Human Brain ◽  
Single Cell ◽  
Progenitor Cells ◽  
Rna Sequencing ◽  
Developmental Trajectory ◽  
Oligodendrocyte Progenitor Cells ◽  
Oligodendrocyte Progenitor ◽  
Single Cell Rna Sequencing
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