Mechanosensitivity of Human Oligodendrocytes

Espinosa-Hoyos, Daniela; Burstein, Suzanne R.; Cha, Jaaram; Jain, Tanya; Nijsure, Madhura P.; Jagielska, Anna; Fossati, Valentina; Vliet, Krystyn J. Van

doi:10.3389/fncel.2020.00222

Cited by 9 publications

(6 citation statements)

References 82 publications

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“…Remarkably, rat primary microglia migrate preferentially towards stiff substrates and exert forces on the substrate that increase with substrate stiffness ( Bollmann et al, 2015 ). Finally, hiPSC-derived oligodendrocytes displayed increased migration with increased stiffness ( Espinosa-Hoyos et al, 2020 ). The myelinating capacity of rat primary OPC was also found to be modulated by substrate stiffness, decreasing on stiff substrates ( Ong et al, 2020 ) ( Figure 7 ).…”

Section: Applications Of Engineered Microenvironments In Neuromechano...mentioning

confidence: 99%

Engineered cell culture microenvironments for mechanobiology studies of brain neural cells

Ransanz

Altena²,

Heine³

et al. 2022

Front. Bioeng. Biotechnol.

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The biomechanical properties of the brain microenvironment, which is composed of different neural cell types, the extracellular matrix, and blood vessels, are critical for normal brain development and neural functioning. Stiffness, viscoelasticity and spatial organization of brain tissue modulate proliferation, migration, differentiation, and cell function. However, the mechanical aspects of the neural microenvironment are largely ignored in current cell culture systems. Considering the high promises of human induced pluripotent stem cell- (iPSC-) based models for disease modelling and new treatment development, and in light of the physiological relevance of neuromechanobiological features, applications of in vitro engineered neuronal microenvironments should be explored thoroughly to develop more representative in vitro brain models. In this context, recently developed biomaterials in combination with micro- and nanofabrication techniques 1) allow investigating how mechanical properties affect neural cell development and functioning; 2) enable optimal cell microenvironment engineering strategies to advance neural cell models; and 3) provide a quantitative tool to assess changes in the neuromechanobiological properties of the brain microenvironment induced by pathology. In this review, we discuss the biological and engineering aspects involved in studying neuromechanobiology within scaffold-free and scaffold-based 2D and 3D iPSC-based brain models and approaches employing primary lineages (neural/glial), cell lines and other stem cells. Finally, we discuss future experimental directions of engineered microenvironments in neuroscience.

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Section: Applications Of Engineered Microenvironments In Neuromechano...mentioning

confidence: 99%

Engineered cell culture microenvironments for mechanobiology studies of brain neural cells

Ransanz

Altena²,

Heine³

et al. 2022

Front. Bioeng. Biotechnol.

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“…Incubation of immortalized rat cerebral endothelial cells with media conditioned with primary rat OPCs resulted in increased expression of tight junction proteins and decreased transwell permeability, indicating a role of OPCs in maintaining the BBB (Seo et al, 2014 ). Lastly, culture of hiPSC-derived OPCs on substrates of varying stiffness has demonstrated that OPC migration is both mechanosensitive and donor-dependent (Espinosa-Hoyos et al, 2020 ).…”

Section: Culture Systemsmentioning

confidence: 99%

Novel Tools and Investigative Approaches for the Study of Oligodendrocyte Precursor Cells (NG2-Glia) in CNS Development and Disease

Galichet

Clayton

Lovell‐Badge

2021

Front. Cell. Neurosci.

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Oligodendrocyte progenitor cells (OPCs), also referred to as NG2-glia, are the most proliferative cell type in the adult central nervous system. While the primary role of OPCs is to serve as progenitors for oligodendrocytes, in recent years, it has become increasingly clear that OPCs fulfil a number of other functions. Indeed, independent of their role as stem cells, it is evident that OPCs can regulate the metabolic environment, directly interact with and modulate neuronal function, maintain the blood brain barrier (BBB) and regulate inflammation. In this review article, we discuss the state-of-the-art tools and investigative approaches being used to characterize the biology and function of OPCs. From functional genetic investigation to single cell sequencing and from lineage tracing to functional imaging, we discuss the important discoveries uncovered by these techniques, such as functional and spatial OPC heterogeneity, novel OPC marker genes, the interaction of OPCs with other cells types, and how OPCs integrate and respond to signals from neighboring cells. Finally, we review the use of in vitro assay to assess OPC functions. These methodologies promise to lead to ever greater understanding of this enigmatic cell type, which in turn will shed light on the pathogenesis and potential treatment strategies for a number of diseases, such as multiple sclerosis (MS) and gliomas.

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“…Each of these chemical signals causes changes to ion channels that drive spontaneous Ca 2+ transients. However, in addition to ion channels that are induced by chemical signals, mechanosensitive ion channels are also present in the nervous system [ 26 , 27 ]. For example, Piezo proteins are mechanosensitive channels that are expressed in the nervous system [ 26 , 28 , 29 ].…”

Section: Introductionmentioning

confidence: 99%

Piezo1-mediated spontaneous calcium transients in satellite glia impact dorsal root ganglia development

Brandt,

Smith

2023

PLoS Biol

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Spontaneous Ca2+ transients of neural cells is a hallmark of the developing nervous system. It is widely accepted that chemical signals, like neurotransmitters, contribute to spontaneous Ca2+ transients in the nervous system. Here, we reveal an additional mechanism of spontaneous Ca2+ transients that is mechanosensitive in the peripheral nervous system (PNS) using intravital imaging of growing dorsal root ganglia (DRG) in zebrafish embryos. GCaMP6s imaging shows that developing DRG satellite glia contain distinct spontaneous Ca2+ transients, classified into simultaneous, isolated, and microdomains. Longitudinal analysis over days in development demonstrates that as DRG satellite glia become more synchronized, isolated Ca2+ transients remain constant. Using a chemical screen, we identify that Ca2+ transients in DRG glia are dependent on mechanical properties, which we confirmed using an experimental application of mechanical force. We find that isolated spontaneous Ca2+ transients of the glia during development is altered by manipulation of mechanosensitive protein Piezo1, which is expressed in the developing ganglia. In contrast, simultaneous Ca2+ transients of DRG satellite glia is not Piezo1-mediated, thus demonstrating that distinct mechanisms mediate subtypes of spontaneous Ca2+ transients. Activating Piezo1 eventually impacts the cell abundance of DRG cells and behaviors that are driven by DRG neurons. Together, our results reveal mechanistically distinct subtypes of Ca2+ transients in satellite glia and introduce mechanobiology as a critical component of spontaneous Ca2+ transients in the developing PNS.

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Mechanosensitivity of Human Oligodendrocytes

Cited by 9 publications

References 82 publications

Engineered cell culture microenvironments for mechanobiology studies of brain neural cells

Engineered cell culture microenvironments for mechanobiology studies of brain neural cells

Novel Tools and Investigative Approaches for the Study of Oligodendrocyte Precursor Cells (NG2-Glia) in CNS Development and Disease

Piezo1-mediated spontaneous calcium transients in satellite glia impact dorsal root ganglia development

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