Mechanical plasticity during oligodendrocyte differentiation and myelination

Domingues, Helena S.; Cruz, Andrea; Chan, Jonah R.; Relvas, João B.; Rubinstein, Boris; Pinto, Inês Mendes

doi:10.1002/glia.23206

Cited by 50 publications

(46 citation statements)

References 70 publications

(121 reference statements)

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“…Likewise, OLG/OPC growth cones and their actin cytoskeletal dynamics are thought to play a key role in guiding the morphological changes associated with each of the stages of the OLG lineage. This idea is consistent with the critical functions ascribed to the actin cytoskeleton in controlling overall OLG morphology (Brown & Macklin, ; Domingues et al, ; Seixas et al, ). Notably, actin cytoskeletal mechanisms do not function in isolation and there is often crosstalk between actin‐ and microtubule‐based cytoskeletal activities.…”

Section: Introductionsupporting

confidence: 87%

The oligodendrocyte growth cone and its actin cytoskeleton: A fundamental element for progenitor cell migration and CNS myelination

Thomason

Escalante

Osterhout

et al. 2019

Glia

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Cells of the oligodendrocyte (OLG) lineage engage in highly motile behaviors that are crucial for effective central nervous system (CNS) myelination. These behaviors include the guided migration of OLG progenitor cells (OPCs), the surveying of local environments by cellular processes extending from differentiating and premyelinating OLGs, and during the process of active myelin wrapping, the forward movement of the leading edge of the myelin sheath's inner tongue along the axon.Almost all of these motile behaviors are driven by actin cytoskeletal dynamics initiated within a lamellipodial structure that is located at the tip of cellular OLG/OPC processes and is structurally as well as functionally similar to the neuronal growth cone. Accordingly, coordinated stoichiometries of actin filament (F-actin) assembly and disassembly at these OLG/OPC growth cones have been implicated in directing process outgrowth and guidance, and the initiation of myelination. Nonetheless, the functional importance of the OLG/OPC growth cone still remains to be fully understood, and, as a unique aspect of actin cytoskeletal dynamics, F-actin depolymerization and disassembly start to predominate at the transition from myelination initiation to myelin wrapping. This review provides an overview of the current knowledge about OLG/OPC growth cones, and it proposes a model in which actin cytoskeletal dynamics in OLG/OPC growth cones are a main driver for morphological transformations and motile behaviors. Remarkably, these activities, at least at the later stages of OLG maturation, may be regulated independently from the transcriptional gene expression changes typically associated with CNS myelination. K E Y W O R D Sactin cytoskeleton, growth cone, migration, myelination, oligodendrocyte

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Section: Introductionsupporting

confidence: 87%

The oligodendrocyte growth cone and its actin cytoskeleton: A fundamental element for progenitor cell migration and CNS myelination

Thomason

Escalante

Osterhout

et al. 2019

Glia

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“…The underlying mechanisms of OPC differentiation have been extensively examined, and several extracellular molecules are identified to promote OPC differentiation (Domingues et al, 2017;Takebayashi & Ikenaka, 2015;Zhang et al, 2016). In addition, the phase-specific expression pattern of transcriptional factors is also well recognized in the function of oligodendrocyte lineage cells (Goldman & Kuypers, 2015).…”

Section: Discussionmentioning

confidence: 99%

“…Mechanisms of OPC differentiation have been extensively examined, and several extrinsic signaling molecules have been identified as regulators of OPC differentiation into oligodendrocytes (Domingues et al, 2017;Takebayashi & Ikenaka, 2015;Zhang, Zhang, & Chopp, 2016). However, while the epigenetic system is known to participate in cell fate decisions, mechanisms as to how the epigenetic regulators contribute to OPC differentiation are still mostly unknown.…”

Section: Introductionmentioning

confidence: 99%

Differential roles of epigenetic regulators in the survival and differentiation of oligodendrocyte precursor cells

Egawa

Shindo

Hikawa

et al. 2018

Glia

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During development or after brain injury, oligodendrocyte precursor cells (OPCs) differentiate into oligodendrocytes to supplement the number of oligodendrocytes. Although mechanisms of OPC differentiation have been extensively examined, the role of epigenetic regulators, such as histone deacetylases (HDACs) and DNA methyltransferase enzymes (DNMTs), in this process is still mostly unknown. Here, we report the differential roles of epigenetic regulators in OPC differentiation. We prepared primary OPC cultures from neonatal rat cortex. Our cultured OPCs expressed substantial amounts of mRNA for HDAC1, HDAC2, DNMT1, and DNMT3a. mRNA levels of HDAC1 and HDAC2 were both decreased by the time OPCs differentiated into myelin‐basic‐protein expressing oligodendrocytes. However, DNMT1 or DNMT3a mRNA level gradually decreased or increased during the differentiation step, respectively. We then knocked down those regulators in cultured OPCs with siRNA technique before starting OPC differentiation. While HDAC1 knockdown suppressed OPC differentiation, HDAC2 knockdown promoted OPC differentiation. DNMT1 knockdown also suppressed OPC differentiation, but unlike HDAC1/2, DNMT1‐deficient cells showed cell damage during the later phase of OPC differentiation. On the other hand, when OPCs were transfected with siRNA for DNMT3a, the number of OPCs was decreased, indicating that DNMT3a may participate in OPC survival/proliferation. Taken together, these data demonstrate that each epigenetic regulator has different phase‐specific roles in OPC survival and differentiation.

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“…Moreover, secondary demyelination is caused by myelin degradation due to neuronal or axonal loss. and migrate to damaged sites in order to remyelinate in response to demyelination events, but this procedure usually is faulty [131]. OLs provide axonal support via insulating myelin, but they also serve a broader role.…”

Section: Communication Between Astrocytes and Mscsmentioning

confidence: 99%

Biomaterial-supported MSCs transplantation enhances cell-cell communication for spinal cord injury

Wang

yang

2020

Preprint

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The spinal cord is part of the central nervous system (CNS) and serves to connect the brain to the peripheral nervous system and peripheral tissues. The cell types that primarily comprise the spinal cord are neurons and several categories of glia, including astrocytes, oligodendrocytes, and microglia. Ependymal cells and small populations of endogenous stem cells, such as oligodendrocyte progenitor cells, also reside in the spinal cord [1]. Neurons are interconnected in circuits; those that process cutaneous sensory input are mainly located in the dorsal spinal cord, while those involved in proprioception and motor control are predominately located in the ventral spinal cord [2]. Due to the importance of the spinal cord, neurodegenerative disorders and traumatic injuries affecting the spinal cord will lead to motor deficits and loss of sensory inputs. Spinal cord injury (SCI), resulting in paraplegia and tetraplegia as a result of deleterious interconnected mechanisms encompassed by the primary and secondary injury, represents a heterogeneously behavioral and cognitive deficit that remains incurable. Following SCI, various barriers containing the neuroinflammation, neural tissue defect (neurons, microglia, astrocytes, and oligodendrocytes), cavity formation, loss of neuronal circuitry and function must be overcame[3]. Notably, the pro -inflammatory and anti-inflammatory effect s of cell-cell communication networks play critical roles in homeostatic, driving the pathophysiologic and consequent cognitive outcomes. In the spinal cord, astrocytes, oligodendrocytes and microglia are involved in not only development but also pathology. Glial cells play dual roles (negative vs. positive effects) in these processes. After SCI, detrimental effects usually dominate and significantly retard functional recovery, and curbing these effects is critical for promoting neurological improvement. Indeed, residential innate immune cells (microglia and astrocytes) and infiltrating leukocytes (macrophages and neutrophils), activated by SCI, give rise to full-blown inflammatory cascades. These inflammatory cells release neurotoxins (proinflammatory cytokines and chemokines, free radicals, excitotoxic amino acids, nitric oxide (NO)), all of which partake in axonal and neuronal deficit[4]. Given the various multifaceted obstacles in SCI treatment, a combinatorial therapy of cell transplantation and biomaterial implantation may be addressed in detail here. For the sake of preserving damaged tissue integrity and providing physical support and trophic supply for axon regeneration, MSCs transplantation has come to the front stage in therapy for SCI with the constant progress of stem cell engineering [5]. MSCs transplantation promotes scaffold integration and regenerative growth potential. Integrating into the implanted scaffold, MSCs influences implant integration by improving the healing process[6]. Conversely, biomaterial scaffolds offer MSCs with a sheltered microenvironment from the surrounding pathological changes, in addition to bridging connection spinal cord stump and offering physical and directional support for axonal regeneration. Besides, Biomaterial scaffolds mimic the extracellular matrix to suppress immune responses. Here, we review the advances in combinatorial biomaterial scaffolds and MSCs transplantation approach that targets certain aspects of various intercellular communications in the pathologic process following SCI. Finally, the challenges of biomaterial-supported MSCs transplantation and its future direction for neuronal regeneration will be presented.

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Mechanical plasticity during oligodendrocyte differentiation and myelination

Cited by 50 publications

References 70 publications

The oligodendrocyte growth cone and its actin cytoskeleton: A fundamental element for progenitor cell migration and CNS myelination

The oligodendrocyte growth cone and its actin cytoskeleton: A fundamental element for progenitor cell migration and CNS myelination

Differential roles of epigenetic regulators in the survival and differentiation of oligodendrocyte precursor cells

Biomaterial-supported MSCs transplantation enhances cell-cell communication for spinal cord injury

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