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NogoA-expressing astrocytes limit peripheral macrophage infiltration after ischemic brain injury in primates

ABSTRACT: NogoA-expressing astrocytes limit peripheral macrophage infiltration after ischemic brain injury in primates

PROVIDER: PRJNA742407 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR14993700_1.fastq.gz	Fastqsanger.gz
	SRR14993700_2.fastq.gz	Fastqsanger.gz
	SRR14993701_1.fastq.gz	Fastqsanger.gz
	SRR14993701_2.fastq.gz	Fastqsanger.gz
	SRR14993702_1.fastq.gz	Fastqsanger.gz

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NogoA-expressing astrocytes limit peripheral macrophage infiltration after ischemic brain injury in primates

Project description:Reactive astrocytes play critical roles after brain injury, but their precise function is not well defined, particularly in humans and nonhuman primates (NHPs). Here, we utilized single nuclei transcriptomics to characterize astrocytes after ischemic stroke in the primary visual cortex (V1) of the marmoset monkey. We observed nearly complete segregation between stroke and control astrocyte clusters. Screening the top 30 differentially expressed genes to identify candidates that might limit stroke recovery, we discovered that RTN4A/ NogoA, a neurite-outgrowth inhibitory protein previously associated specifically with oligodendrocytes but not astrocytes, was expressed in a majority of reactive astrocytes. Robust NogoA upregulation on reactive astrocytes following stroke was confirmed in both the marmoset and human brain, whereas rodents exhibited only a marginal change in NogoA expression following stroke. Further, in vivo and in vitro studies determined that NogoA mediated an anti-inflammatory response which likely contributes to limiting deeper infiltration of peripheral macrophages into the surviving parenchyma during the subacute post-stroke period. These findings are directly relevant to the development of NogoA-targeting therapies designed for clinical use shortly after ischemic stroke. In addition, our data have uncovered the complexity of astrocyte responses in primates, which highlights the importance of preclinical model selection for discovery research designed to identify novel therapeutics for brain injury.

2021-10-18 | GSE179141 | GEO

NogoA-expressing astrocytes limit peripheral macrophage infiltration after ischemic brain injury in primates.

Project description:Astrocytes play critical roles after brain injury, but their precise function is poorly defined. Utilizing single-nuclei transcriptomics to characterize astrocytes after ischemic stroke in the visual cortex of the marmoset monkey, we observed nearly complete segregation between stroke and control astrocyte clusters. Screening for the top 30 differentially expressed genes that might limit stroke recovery, we discovered that a majority of astrocytes expressed RTN4A/ NogoA, a neurite-outgrowth inhibitory protein previously only associated with oligodendrocytes. NogoA upregulation on reactive astrocytes post-stroke was significant in both the marmoset and human brain, whereas only a marginal change was observed in mice. We determined that NogoA mediated an anti-inflammatory response which likely contributes to limiting the infiltration of peripheral macrophages into the surviving parenchyma.

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Extragenous ILC2s infiltration into the brain after ischemic stroke

Project description:Extragenous ILC2s infiltration into the brain after ischemic stroke

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Single-Cell Transcriptomic Analysis of Astrocytes 12 Hours after Ischemic Stroke.

Project description:Reactive astrocytes are detrimental or protective in ischemic stroke. However, the mechanisms of these effects are not entirely clear. We investigated the heterogeneity of mice astrocytes 12 h after cerebral ischemia-reperfusion via Single-cell RNA sequencing. We acquired astrocyte subclusters’ transcriptional characteristics involving diversified functions. We identified 9 genes as potential therapeutic targets and 6 genes were specific to astrocyte subcluster 2. Additionally, we explored the effects of melatonin and stattic on the transformation of astrocytes to the A2 phenotype. TTC stain, grip strength test and immunofluorescence were used. We revealed melatonin promoted the transformation of astrocytes to the A2 phenotype, the effect was related to STAT3 and inhibited by Stattic. Our study may lay a foundation for untangling the difference between astrocyte subclusters 12 h after stroke and elucidating the mechanisms of A2 astrocyte transformation 3 d after stroke.

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Dysregulation of principal circulating miRNAs in Nonhuman Primates following ischemic stroke

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Long noncoding RNA expression profiles in brain ischemic tolerance by cerebral ischemic preconditioning

Project description:In this study, cerebral cortical astrocytes and neurons of rats were co-cultured, the astrocytes of the co-cultured cell model pretreated by ischemic preconditioning (45 min of OGD) were subjected to lncRNA high-throughput sequencing (RNA-seq).

2021-11-01 | GSE185931 | GEO

Single-Cell Transcriptomic Analysis of Astrocytes 12 Hours after Ischemic Stroke.

Project description:Single-Cell Transcriptomic Analysis of Astrocytes 12 Hours after Ischemic Stroke.

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Project description:Primates Raw sequence reads

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