Time-course analysis of astrocyte-specific RNA-seq in two severities of spinal cord injury
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE96054 | GEO | 2017/03/10
SECONDARY ACCESSION(S): PRJNA378671
REPOSITORIES: GEO
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Project description:Spinal cord injury (SCI) is a common but devastating trauma of the central nerve system. In this study, we reprogrammed cultured spinal-cord reactive astrocytes into neurons by Neurod1 expression. The mechanism of programmed conversion from astrocytes to neurons has not been clarified yet. Thus, we used label-free proteomics to identify differentially expressed proteins in Neurod1 over-expressed astrocytes and control group. A total of 1952 proteins were identified, including 92 significantly changed proteins. Among these proteins, 8 proteins were identified as candidates involving in the process of the reprogramming, based on their biological function and fold change in the bioinformatic analysis. Our study revealed that that Neurod1 can directly reprogram cultured spinal-cord reactive astrocytes into neurons, and several proteins that could play a significant role during the neuronal reprogramming were discovered.
2021-09-08 | PXD016097 | Pride
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
Project description:We demonstrate for the first time that the extracellular matrix glycoprotein Tenascin-C regulates the expression of key patterning genes during late embryonic spinal cord development, leading to a timely maturation of gliogenic neural precursor cells. We first show that Tenascin-C is expressed by gliogenic neural precursor cells during late embryonic development. The loss of Tenascin-C leads to a sustained generation and delayed migration of Fibroblast growth factor receptor 3 expressing immature astrocytes in vivo. Furthermore, we could demonstrate an upregulation of Nk2 transcription factor related locus 2 (Nkx2.2) and its downstream target Sulfatase 1 in vivo. A dorsal expansion of Nkx2.2-positive cells within the ventral spinal cord indicates a potential progenitor cell domain shift. Moreover, Sulfatase 1 is known to regulate growth factor signalling by cleaving sulphate residues from heparan sulphate proteoglycans. Consistent with this possibility we observed changes in both Fibroblast growth factor 2 and Epidermal growth factor responsiveness of spinal cord neural precursor cells. Taken together our data clearly show that Tenascin-C promotes the astroglial lineage progression during spinal cord development. in total 6 probes: 3 replica of TNC_wt and 3 replica of TNC_ko
2011-10-19 | E-GEOD-33091 | biostudies-arrayexpress
Project description:Analysis of gene expression by astrocytes or non-astrocyte cells in spinal cord injury (SCI) lesions may lead to the identification of molecules that impact on axon regrowth. We conducted genome-wide RNA sequencing of (i) immunoprecipitated astrocyte-specific ribosome-associated RNA (ramRNA) from WT or STAT3-CKO astrocytes, and (ii) the non-precipitated (flow-through) RNA deriving from non-astrocyte cells in the same tissue samples 14 days following SCI. DOI: 10.1038/nature17623 Young adult female mGFAP-Cre-RiboTag or mGFAP-Cre-RiboTag-STAT3-LoxP mice underwent severe crush SCI at thoracic level 10. 14 days following SCI, the central 3mm of the SCI lesion was extracted, homogenized and (i) astrocyte-specific ribosome-associated RNA (ramRNA) precipitated via a hemagglutinin (HA) tag targeted to either WT (n=4) or STAT3-CKO (n=3) astrocytes, and (ii) the non-precipitated (flow-through) RNA deriving from non-astrocyte cells in the same tissue samples. Sex and age-matched mGFAP-Cre-RiboTag mice served as uninjured controls (n=4).
2016-03-30 | E-GEOD-76097 | biostudies-arrayexpress
Project description:We conducted snRNAseq of mouse astrocytes after traumatic spinal cord injury (SCI). These data reveal transcriptomic similarities and differences among astrocytes in healthy spinal cord and after spinal cord injury.
2024-01-09 | GSE247844 | GEO
Project description:Analysis of gene expression by astrocytes or non-astrocyte cells in spinal cord injury (SCI) lesions may lead to the identification of molecules that impact on axon regrowth. We conducted genome-wide RNA sequencing of (i) immunoprecipitated astrocyte-specific ribosome-associated RNA (ramRNA) from WT or STAT3-CKO astrocytes, and (ii) the non-precipitated (flow-through) RNA deriving from non-astrocyte cells in the same tissue samples 14 days following SCI. DOI: 10.1038/nature17623
2016-03-30 | GSE76097 | GEO
Project description:Aggressive inflammation and excessive scar formation are the main cause to the difficulty of neural tissue repair after spinal cord injury (SCI). Microglia and astrocytes act as important role in this micro-environment of SCI and there is cross regulation between microglia and astrocytes. After SCI, MG0 polarized into MG1 and MG3 which were belong to pro-inflammatory phenotype microglia; Naive astrocytes polarized into Reactive and Scar-forming astrocytes. Growth arrest-specific 6 (Gas6) and its receptor Axl was declined in all these cells after SCI. In vitro study, Gas6 had the negative effect on cytotoxic astrocytes and pro-inflammatory microglia polarization and even the cross regulation between cytotoxic astrocytes and pro-inflammatory microglia. Further mechanism study indicated that Gas6 suppressed cytotoxic phenotype polarization of astrocytes through inhibited the activation of YES-associated protein (YAP) signal pathway and suppressed pro-inflammatory phenotype polarization of microglia through inhibited the activation of NF-κB/p65 and JAK/Stat3 signal pathways. In vivo study, Gas6 treatment suppressed cytotoxic astrocytes and pro-inflammatory microglia polarization at the injured site of spinal cord to facilitate tissue repair and loco-motor recovery.
2023-10-21 | GSE245470 | GEO
Project description:Astrocytes are taking the center stage in neurotrauma and neurological disease as they appear to play a dominant role in the inflammatory processes associated with these conditions. Previously, we reported that inhibiting nuclear factor kappa B (NF-kB) activation in astrocytes, by using a transgenic mouse model (GFAP-IκBα-dn mice), results in improved functional recovery following spinal cord injury (SCI), with increased white matter preservation and axonal sparing. In the present study we sought to determine whether this improvement, due to inhibiting NF-k-B activation in astrocytes, could be the result of enhanced oligogenesis in our GFAP-IκBα-dn mice. To gain insight into the underlying molecular mechanisms, we performed microarray analysis in naïve and 3 days, 3 and 6 weeks following SCI in GFAP-IκBα-dn and wild type (WT) littermate mice. Surprisingly, we found the largest number of genes differentially regulated between GFAP-IκBα-dn and WT mice 6 weeks post-injury. Interestingly, the data suggested that inhibiting astroglial NF-kB alters the inflammatory environment to support oligogenesis. Furthermore, confirmation of microarray data with qPCR and western blotting analysis and using BrdU labeling along with cell specific immunohistochemistry, confocal microscopy and quantitative cell counts, we demonstrate a significant increase in oligogenesis in GFAP-IκBα-dn following SCI. These studies suggest that therapeutic strategies targeting NF-kB activation in the CNS following SCI may promote oligogenesis and remyelination. Wild type (WT) mice - time points naïve, 3 days, 3 weeks, 6 weeks. Transgenic mice (TG) - time points naïve, 3 days, 3 weeks, 6 weeks.
2013-09-01 | E-GEOD-46695 | biostudies-arrayexpress
Project description:We demonstrate for the first time that the extracellular matrix glycoprotein Tenascin-C regulates the expression of key patterning genes during late embryonic spinal cord development, leading to a timely maturation of gliogenic neural precursor cells. We first show that Tenascin-C is expressed by gliogenic neural precursor cells during late embryonic development. The loss of Tenascin-C leads to a sustained generation and delayed migration of Fibroblast growth factor receptor 3 expressing immature astrocytes in vivo. Furthermore, we could demonstrate an upregulation of Nk2 transcription factor related locus 2 (Nkx2.2) and its downstream target Sulfatase 1 in vivo. A dorsal expansion of Nkx2.2-positive cells within the ventral spinal cord indicates a potential progenitor cell domain shift. Moreover, Sulfatase 1 is known to regulate growth factor signalling by cleaving sulphate residues from heparan sulphate proteoglycans. Consistent with this possibility we observed changes in both Fibroblast growth factor 2 and Epidermal growth factor responsiveness of spinal cord neural precursor cells. Taken together our data clearly show that Tenascin-C promotes the astroglial lineage progression during spinal cord development.
2011-10-20 | GSE33091 | GEO