Neuronal contact upregulates astrocytic sphingosine‐1‐phosphate receptor 1 to coordinate astrocyte‐neuron cross communication

Singh, Sandeep Kumar; Kordula, Tomasz; Spiegel, Sarah

doi:10.1002/glia.24135

Cited by 24 publications

(13 citation statements)

References 66 publications

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“…On the other hand, although the radioactive signal of [ 3 H]CS1P1 was much stronger in the gray matter than that in the white matter, a faint distribution of [ 3 H]CS1P1 was also observed in the white matter regions, and the overall distribution of [ 3 H]CS1P1 was more comparable to GFAP staining rather than NeuN and IBA1 staining. This was consistent with the fact that S1PR1 is ubiquitously expressed in various types of brain cells at relatively low-to-mild levels but highly expressed by astrocytes. , …”

Section: Resultssupporting

confidence: 88%

Quantitative Analysis of S1PR1 Expression in the Postmortem Multiple Sclerosis Central Nervous System

Jiang,

Zhou,

Qiu

et al. 2023

ACS Chem. Neurosci.

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Multiple sclerosis (MS) is an immune-mediated disease that is characterized by demyelination and inflammation in the central nervous system (CNS). Previous studies demonstrated that sphingosine-1-phosphate receptor (S1PR) modulators effectively inhibit S1PR1 in immune cell trafficking and reduce entry of pathogenic cells into the CNS. Studies have also implicated a nonimmune, inflammatory role of S1PR1 within the CNS in MS. In this study, we explored the expression of S1PR1 in the development and progression of demyelinating pathology of MS by quantitative assessment of S1PR1 expression using our S1PR1-specific radioligand, [ 3 H]CS1P1, in the postmortem human CNS tissues including cortex, cerebellum, and spinal cord of MS cases and age-and sex-matched healthy cases. Immunohistochemistry with whole slide scanning for S1PR1 and various myelin proteins was also performed. Autoradiographic analysis using [ 3 H]CS1P1 showed that the expression of S1PR1 was statistically significantly elevated in lesions compared to nonlesion regions in the MS cases, as well as normal healthy controls. The uptake of [ 3 H]CS1P1 in the gray matter and nonlesion white matter did not significantly differ between healthy and MS CNS tissues. Saturation autoradiography analysis showed an increased binding affinity (K d ) of [ 3 H]CS1P1 to S1PR1 in both gray matter and white matter of MS brains compared to healthy brains. Our blocking study using NIBR-0213, a S1PR1 antagonist, indicated [ 3 H]CS1P1 is highly specific to S1PR1. Our findings demonstrated the activation of S1PR1 and an increased uptake of [ 3 H]CS1P1 in the lesions of MS CNS. In summary, our quantitative autoradiography analysis using [ 3 H]CS1P1 on human postmortem tissues shows the feasibility of novel imaging strategies for MS by targeting S1PR1.

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Section: Resultssupporting

confidence: 88%

Quantitative Analysis of S1PR1 Expression in the Postmortem Multiple Sclerosis Central Nervous System

Jiang,

Zhou,

Qiu

et al. 2023

ACS Chem. Neurosci.

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“…Moreover, multiple genes were found that are known to be specifically upregulated during astrocyte-neuron interactions and coordinated maturation, e.g. SPARCL1 36 , METRN 37,38 and CROC4 39 .…”

Section: Single-cell Rna Sequencing Confirms Maturation Of Astrocytes...mentioning

confidence: 99%

Rapid specification of human pluripotent stem cells to functional astrocytes

Lendemeijer

Unkel

Mossink

et al. 2022

Preprint

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Astrocytes are essential for the formation and maintenance of neural networks through metabolic support, facilitation of synaptic function, and optimization of electrophysiological activity. However, a major technical challenge for investigating astrocyte function and disease-related pathophysiology has been the limited ability to obtain functional human astrocytes. Here we present a novel method to efficiently differentiate human pluripotent stem cell (hPSC)-derived neural progenitors to functional astrocytes in 28 days using a culture medium containing leukemia inhibitory factor (LIF) and bone morphogenetic protein 4 (BMP4). This approach yields highly pure populations of astrocytes expressing canonical astrocyte markers, which we confirmed by immunofluorescence, flow cytometry and RNA sequencing. Human PSC-derived astrocytes efficiently buffer glutamate and robustly support neural network activity. Co-cultures of hPSC-derived astrocytes and neurons on multi-electrode arrays generated robust network activity within 2 days and synchronous network bursts after 6 days. Whole cell patch-clamp recordings revealed an increased frequency of postsynaptic currents in human hPSC-derived neurons co-cultured with hPSC-derived versus primary rodent astrocytes, consistent with a corresponding increase in synapse density. Furthermore, hPSC-derived astrocytes retained their hominid morphology when transplanted into a mouse brain. In conclusion, we present a novel protocol to obtain functional astrocytes from human pluripotent stem cells, providing a platform for investigating human astrocyte function and neuronal-glial interactions.

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“…Interestingly, the S1pr1 GPCR has been shown to regulate germ cell migration in the ascidian B. schlosseri (Kassmer et al ., 2015), similar to the role of Tre1 GPCR in Drosophila germ cells (Kunwar et al ., 2003). In addition, in vitro studies have suggested that S1pr1 can regulate astrocyte morphology in mammals (Singh et al, 2021). By whole-mount in situ hybridization, we validated that s1pr1 was expressed in zebrafish larval brain and spinal cord at 3 dpf (Figure S5D).…”

Section: Resultsmentioning

confidence: 99%

Astrocyte growth during morphogenesis is driven by the Tre1/S1pr1 phospholipid-binding G protein-coupled receptor

Chen

Stork

Kang

et al. 2022

Preprint

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Astrocytes play crucial roles in regulating neural circuit function by forming a dense network of synapse-associated membrane specializations. Intimate astrocyte-synapse contact is thought to be crucial for astrocyte function, yet signaling pathways regulating astrocyte morphogenesis remain poorly defined. Here we show the Drosophila lipid-binding G protein-coupled receptor (GPCR) Tre1, likely acting through Rac1, is required for astrocytes to elaborate their complex morphologies. The lipid phosphate phosphatases Wunen/Wunen2, which process phospholipid ligands for Tre1, also regulate astrocyte growth, and act upstream of Tre1 as Wunen/Wunen2-mediated astrocyte overgrowth is suppressed by Tre1 loss. Loss of s1pr1, the functional analog of Tre1 in zebrafish, also leads to disruption of astrocyte morphogenesis. Live-imaging and pharmacology demonstrate that S1pr1 balances proper astrocyte process extension/retraction dynamics during morphogenesis, and that S1pr1 signaling is required throughout astrocyte development. Our work identifies lipid-binding GPCRs like Tre1 and S1pr1 as potent evolutionarily conserved regulators of astrocyte morphological complexity.

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Neuronal contact upregulates astrocytic sphingosine‐1‐phosphate receptor 1 to coordinate astrocyte‐neuron cross communication

Cited by 24 publications

References 66 publications

Quantitative Analysis of S1PR1 Expression in the Postmortem Multiple Sclerosis Central Nervous System

Quantitative Analysis of S1PR1 Expression in the Postmortem Multiple Sclerosis Central Nervous System

Rapid specification of human pluripotent stem cells to functional astrocytes

Astrocyte growth during morphogenesis is driven by the Tre1/S1pr1 phospholipid-binding G protein-coupled receptor

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