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Systematic analysis of purified astrocytes after spinal cord injury unveils lncRNA Zeb2os as a novel molecular target for astrogliosis

ABSTRACT: Systematic analysis of purified astrocytes after spinal cord injury unveils lncRNA Zeb2os as a novel molecular target for astrogliosis

PROVIDER: PRJNA643794 | ENA |

REPOSITORIES: ENA

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Systematic analysis of purified astrocytes after spinal cord injury unveils lncRNA Zeb2os as a novel molecular target for astrogliosis [RNA-Seq]

Project description:Astrocytes are the predominant component of the scar and play crucial roles in spinal cord injury (SCI) at acute injury stage. Understanding the complex reactive astroglial contributions to SCI pathophysiologies is important for developing therapeutic strategies. To understand the mechanisms of astrogliosis in SCI, and to identify novel molecular targets to improve the injury environment and axonal regeneration, we have studied gene expression changes in SCI epicenter tissue using RNA-Seq at chronic stages (1 month and 3 months) in mouse moderate contusive injury models. Importantly, we have also FACS purified cells successfully from adult spinal cord using transgenic mice and generated RNA-Seq results for both acute (7 days) and chronic (1 month and 3 months) injury stages. The SCI RNA-Seq analysis provided valuable information on the gene expression in injury environment and astrocytes after SCI. In addition to protein coding genes, we were the first to systematically analyze the expression profiles of Long Noncoding RNAs (lncRNAs) in SCI and purified astrocytes. We have tested a number of candidates and found gene of interest Zeb2os which is a highly conserved lncRNA in human. Zeb2os expression has high correlation with an essential transcription factor (TF) in astrogliosis, Stat3, and its antisense protein coding gene Zeb2. Furthermore, our ChIP-seq experiment showed STAT3 bound to Zeb2 promoter region, thus Zeb2os may regulate Zeb2 and Stat3 directly or indirectly and STAT3 may regulate Zeb2 expression. Moreover, we have demonstrated for the first time by shRNA gene knockdown (KD) and functional assays that Zeb2os plays an important functional role in astrogliosis. We found Zeb2os KD in primary astrocytes affected a number of downstream genes by RNA-Seq, for example, Gfap, Zeb2, and Stat3 level decreased and reduced astrocyte proliferation.

2021-02-08 | GSE153720 | GEO

Systematic analysis of purified astrocytes after spinal cord injury unveils lncRNA Zeb2os as a novel molecular target for astrogliosis [ChIP-Seq]

Project description:Astrocytes are the predominant component of the scar and play crucial roles in spinal cord injury (SCI) at acute injury stage. Understanding the complex reactive astroglial contributions to SCI pathophysiologies is important for developing therapeutic strategies. To understand the mechanisms of astrogliosis in SCI, and to identify novel molecular targets to improve the injury environment and axonal regeneration, we have studied gene expression changes in SCI epicenter tissue using RNA-Seq at chronic stages (1 month and 3 months) in mouse moderate contusive injury models. Importantly, we have also FACS purified cells successfully from adult spinal cord using transgenic mice and generated RNA-Seq results for both acute (7 days) and chronic (1 month and 3 months) injury stages. The SCI RNA-Seq analysis provided valuable information on the gene expression in injury environment and astrocytes after SCI. In addition to protein coding genes, we were the first to systematically analyze the expression profiles of Long Noncoding RNAs (lncRNAs) in SCI and purified astrocytes. We have tested a number of candidates and found gene of interest Zeb2os which is a highly conserved lncRNA in human. Zeb2os expression has high correlation with an essential transcription factor (TF) in astrogliosis, Stat3, and its antisense protein coding gene Zeb2. Furthermore, our ChIP-seq experiment showed STAT3 bound to Zeb2 promoter region, thus Zeb2os may regulate Zeb2 and Stat3 directly or indirectly and STAT3 may regulate zeb2 expression. Moreover, we have demonstrated for the first time by shRNA gene knockdown (KD) and functional assays that Zeb2os plays an important functional role in astrogliosis. We found Zeb2os KD in primary astrocytes affected a number of downstream genes by RNA-Seq, for example, Gfap, Zeb2, and Stat3 level decreased and reduced astrocyte proliferation.

2021-02-08 | GSE153085 | GEO

Systematic analysis of purified astrocytes after spinal cord injury unveils lncRNA Zeb2os as a novel molecular target for astrogliosis [ChIP-Seq]

Project description:Systematic analysis of purified astrocytes after spinal cord injury unveils lncRNA Zeb2os as a novel molecular target for astrogliosis [ChIP-Seq]

| PRJNA641406 | ENA

Systematic analysis of purified astrocytes after spinal cord injury unveils lncRNA Zeb2os as a novel molecular target for astrogliosis [RNA-Seq]

Project description:Systematic analysis of purified astrocytes after spinal cord injury unveils lncRNA Zeb2os as a novel molecular target for astrogliosis [RNA-Seq]

| PRJNA643800 | ENA

Expression data from reactive astrocytes acutely purified from young adult mouse brains

Project description:Reactive astrogliosis is characterized by a profound change in astrocyte phenotype in response to all CNS injuries and diseases. To better understand the reactive astrocyte state, we used Affymetrix GeneChip arrays to profile gene expression in populations of reactive astrocytes isolated at various time points after induction using two different mouse injury models, ischemic stroke and neuroinflammation. Young adult male mice underwent middle cerebral artery occlusion (MCAO) to produce ischemic stroke or control sham surgery. Young adult mice were injected intraperitoneally with 5 mg/kg lipopolysaccharide (LPS) to produce neuroinflammation or saline for control. Astrocytes were acutely purified from control and injured brains at 1 day after injury for LPS/saline injection and 1, 3 days and 7 days after MCAO/sham surgeries.

2012-05-01 | E-GEOD-35338 | biostudies-arrayexpress

Systematic analysis of purified astrocytes after spinal cord injury unveils lncRNA Zeb2os as a novel molecular target for astrogliosis

Project description:This SuperSeries is composed of the SubSeries listed below.

2021-02-08 | GSE153721 | GEO

Direct Reprogramming of Human Astrocytes into Spinal Cord Organoids Facilitating Spinal Cord Regeneration

Project description:Human astrocytes have reported to reprogram into neurons, but they have yet to be induced to three-dimensional (3D) neural tissue for neural organogenesis. Here, we demonstrate a remarkable strategy for 3D organoid generation by direct reprogramming human astrocytes. By combining overexpression OCT4, suppression p53 and small molecules CHIR99021, SB431542, RepSox and Y27632, termed as Op53-CSBRY, we successfully reprogramed human astrocytes into neural ectodermal cells and further induced human 3D-brain organoid. Those organoids can be finally induced into spinal cord organoids by activating FGF, SHH and BMP signaling. The grafts of Human astrocyte derived spinal cord organoids (hADSC-Organs) can survived, differentiated into spinal cord neurons, migrated long distance, formed synaptic connectivity with host neurons, bridged complete injury spinal cord tissue in mice. This method indicates that human astrocytes could be directly triggered neural organogenesis, and may hold a great promising to support local astrocytes in situ organogenesis after brain damages, such as stroke and spinal cord injury.

2024-02-01 | GSE168635 | GEO

Expression data from reactive astrocytes acutely purified from young adult mouse brains

2012-05-02 | GSE35338 | GEO

Systematic analysis of purified astrocytes after SCI unveils Zeb2os function during astrogliosis.

Project description: Not available

| S-EPMC7920574 | biostudies-literature

Regional spinal cord gene expression profiling of adult astrocytes

Project description:There is emerging evidence that astrocytes exhibit molecular and cellular heterogeneity; however, whether distinct subpopulations perform these diverse roles remains poorly defined. Previous studies used Aldhl1l1 as a bulk astrocyte marker. Here we show that the Lunatic Fringe-GFP (Lfng-GFP) bacteria artificial chromosome mouse line specifically labels astrocyte populations within lamina III and IV of the dorsal spinal cord. We compared the transcriptional profile of Lfng-GFP+ astrocytes with Aldh1l1-GFP astrocytes to identify what is unique about the astrocyte population.

2021-10-25 | GSE186410 | GEO

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