CD44 is required for the migration of transplanted oligodendrocyte progenitor cells to focal inflammatory demyelinating lesions in the spinal cord

Glia ◽  
2012 ◽  
Vol 61 (3) ◽  
pp. 361-367 ◽  
Author(s):  
Jing-Hua Piao ◽  
Yanping Wang ◽  
Ian D. Duncan
Keyword(s):  
Spinal Cord ◽  
Progenitor Cells ◽  
Oligodendrocyte Progenitor Cells ◽  
Oligodendrocyte Progenitor ◽  
Demyelinating Lesions

The fate and function of oligodendrocyte progenitor cells after traumatic spinal cord injury

Glia ◽  
2019 ◽  
Vol 68 (2) ◽  
pp. 227-245 ◽  
Author(s):  
Greg J. Duncan ◽  
Sohrab B. Manesh ◽  
Brett J. Hilton ◽  
Peggy Assinck ◽  
Jason R. Plemel ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Progenitor Cells ◽  
Traumatic Spinal Cord Injury ◽  
Oligodendrocyte Progenitor Cells ◽  
Oligodendrocyte Progenitor ◽  
Cord Injury ◽  
And Function

Migration and remyelination by oligodendrocyte progenitor cells transplanted adjacent to focal areas of spinal cord inflammation

2011 ◽  
Vol 89 (11) ◽  
pp. 1737-1746 ◽  
Author(s):  
Yanping Wang ◽  
Jing-Hua Piao ◽  
Eric C. Larsen ◽  
Yoichi Kondo ◽  
Ian D. Duncan
Keyword(s):  
Spinal Cord ◽  
Progenitor Cells ◽  
Oligodendrocyte Progenitor Cells ◽  
Oligodendrocyte Progenitor

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 Reactive oligodendrocyte progenitor cells (re-)myelinate the regenerating zebrafish spinal cord

Development ◽  
2020 ◽  
Vol 147 (24) ◽  
pp. dev193946 ◽  
Author(s):  
Vasiliki Tsata ◽  
Volker Kroehne ◽  
Daniel Wehner ◽  
Fabian Rost ◽  
Christian Lange ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Progenitor Cells ◽  
Transcriptional Profiling ◽  
Oligodendrocyte Progenitor Cells ◽  
Lesion Site ◽  
Oligodendrocyte Progenitor ◽  
Functional Deficits ◽  
Myelin Sheaths ◽  
Cord Injury ◽  
Global Reduction

ABSTRACTSpinal cord injury (SCI) results in loss of neurons, oligodendrocytes and myelin sheaths, all of which are not efficiently restored. The scarcity of oligodendrocytes in the lesion site impairs re-myelination of spared fibres, which leaves axons denuded, impedes signal transduction and contributes to permanent functional deficits. In contrast to mammals, zebrafish can functionally regenerate the spinal cord. Yet, little is known about oligodendroglial lineage biology and re-myelination capacity after SCI in a regeneration-permissive context. Here, we report that, in adult zebrafish, SCI results in axonal, oligodendrocyte and myelin sheath loss. We find that OPCs, the oligodendrocyte progenitor cells, survive the injury, enter a reactive state, proliferate and differentiate into oligodendrocytes. Concomitantly, the oligodendrocyte population is re-established to pre-injury levels within 2 weeks. Transcriptional profiling revealed that reactive OPCs upregulate the expression of several myelination-related genes. Interestingly, global reduction of axonal tracts and partial re-myelination, relative to pre-injury levels, persist at later stages of regeneration, yet are sufficient for functional recovery. Taken together, these findings imply that, in the zebrafish spinal cord, OPCs replace lost oligodendrocytes and, thus, re-establish myelination during regeneration.

scholarly journals Overcoming the inhibitory microenvironment surrounding oligodendrocyte progenitor cells following experimental demyelination

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Darpan Saraswat ◽  
Hani J. Shayya ◽  
Jessie J. Polanco ◽  
Ajai Tripathi ◽  
R. Ross Welliver ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Progenitor Cells ◽  
Demyelinating Disease ◽  
Heparan Sulfate Proteoglycans ◽  
Oligodendrocyte Progenitor Cells ◽  
Subsequent Generation ◽  
Oligodendrocyte Progenitor ◽  
Demyelinating Lesions ◽  
Experimental Demyelination

AbstractChronic demyelination in the human CNS is characterized by an inhibitory microenvironment that impairs recruitment and differentiation of oligodendrocyte progenitor cells (OPCs) leading to failed remyelination and axonal atrophy. By network-based transcriptomics, we identified sulfatase 2 (Sulf2) mRNA in activated human primary OPCs. Sulf2, an extracellular endosulfatase, modulates the signaling microenvironment by editing the pattern of sulfation on heparan sulfate proteoglycans. We found that Sulf2 was increased in demyelinating lesions in multiple sclerosis and was actively secreted by human OPCs. In experimental demyelination, elevated OPC Sulf1/2 expression directly impaired progenitor recruitment and subsequent generation of oligodendrocytes thereby limiting remyelination. Sulf1/2 potentiates the inhibitory microenvironment by promoting BMP and WNT signaling in OPCs. Importantly, pharmacological sulfatase inhibition using PI-88 accelerated oligodendrocyte recruitment and remyelination by blocking OPC-expressed sulfatases. Our findings define an important inhibitory role of Sulf1/2 and highlight the potential for modulation of the heparanome in the treatment of chronic demyelinating disease.

scholarly journals Overcoming the inhibitory microenvironment surrounding oligodendrocyte progenitor cells following demyelination

2020 ◽  
Author(s):  
Darpan Saraswat ◽  
Hani J. Shayya ◽  
Jessie J. Polanco ◽  
Ajai Tripathi ◽  
R. Ross Welliver ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Progenitor Cells ◽  
Demyelinating Disease ◽  
Heparan Sulfate Proteoglycans ◽  
Oligodendrocyte Progenitor Cells ◽  
Subsequent Generation ◽  
Oligodendrocyte Progenitor ◽  
Demyelinating Lesions ◽  
Experimental Demyelination

Chronic demyelination in the human CNS is characterized by an inhibitory microenvironment that impairs recruitment and differentiation of oligodendrocyte progenitor cells (OPCs) leading to failed remyelination and axonal atrophy. By network-based transcriptomics, we identified sulfatase 2 (Sulf2) mRNA in activated human primary OPCs. Sulf2, an extracellular endosulfatase, modulates the signaling microenvironment by editing the pattern of sulfation on heparan sulfate proteoglycans. We found that Sulf2 was increased in demyelinating lesions in multiple sclerosis and was actively secreted by human OPCs. In experimental demyelination, elevated OPC Sulf1/2 expression directly impaired progenitor recruitment and subsequent generation of oligodendrocytes thereby limiting remyelination. Sulf1/2 potentiates the inhibitory microenvironment by promoting BMP and WNT signaling in OPCs. Importantly, pharmacological sulfatase inhibition using PI-88 accelerated oligodendrocyte recruitment and remyelination by blocking OPC-expressed sulfatases. Our findings define an important inhibitory role of Sulf1/2 and highlight the potential for modulation of the heparanome in the treatment of chronic demyelinating disease.

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.

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