Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Transcriptomic profile of reactive astrocytes induced by activation of the JAK2-STAT3 pathway in mouse striatal astrocytes

ABSTRACT: We analyzed the transcriptional profile of normal astrocytes and astrocytes made reactive by AAV gene transfer of a contitutive form of JAK2 (JAK2ca). We show that activation of the JAK2-STAT3 pathway by JAK2ca induces significant transcriptional changes in astrocytes, recapitulating several molecular hallmarks of reactivity

ORGANISM(S): Mus musculus

PROVIDER: GSE107486 | GEO | 2022/06/29

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Similar Datasets

Transcriptomic profile of reactive astrocytes induced by activation of the JAK2-STAT3 pathway in mouse striatal astrocytes

Project description:Transcriptomic profile of reactive astrocytes induced by activation of the JAK2-STAT3 pathway in mouse striatal astrocytes

| PRJNA420366 | ENA

RNAseq analysis of FACS-isolated astrocytes from the striatum of 11-14 month-old knock-in Hdh140 mice after astrocyte-targeted expression of GFAP or JAK2ca

Project description:We analyzed the transcriptional profile of striatal astrocytes from 1) Hdh140 mice infected with AAV-GFP, 2) astrocytes from Hdh140 mice infected with AAV-JAK2ca (+ AAV-GFP, at the same total virus load). We show that JAK2ca activates the JAK2-STAT3 patwhay in striatal astrocytes, induces reactive changes and activates a proteostasis signature.

2022-03-18 | GSE171141 | GEO

Reactive astrocytes in ALS display dysregulated intron retention

Project description:Reactive astrocytes are implicated in amyotrophic lateral sclerosis (ALS), although the mechanisms controlling reactive transformation are unknown. We show that decreased intron retention (IR) is common to human iPSC-derived astrocytes carrying VCP, C9orf72 and SOD1 ALS-causing mutations as well as astrocytes stimulated to undergo reactive transformation. Notably, transcripts with decreased IR and increased expression are overrepresented in reactivity processes including cell-adhesion, stress-response, and immune-activation. We examined translatome sequencing (TRAP-seq) of astrocytes from a SOD1 mouse model, which revealed that transcripts upregulated in translation significantly overlap with transcripts with decreased IR. Using nucleo-cytoplasmic fractionation of VCP astrocytes coupled with mRNA sequencing and proteomics, we identify that decreased IR in nuclear-detained transcripts is associated with increased cytoplasmic expression of genes and proteins encoding regulators of reactivity - indicating nuclear-to-cytoplasmic translocation and translation of spliced reactivity-related transcripts. Our study provides important insights into the molecular regulation of reactive transformation of ALS astrocytes.

2021-09-09 | PXD022604 | Pride

Reactive astrocytes in ALS models display dysregulated intron retention

Project description:Reactive astrocytes are implicated in Amyotrophic Lateral Sclerosis (ALS), although the mechanisms controlling reactive transformation are unknown. We show that decreased intron retention (IR) is common to human induced pluripotent stem cell (hiPSC)-derived astrocytes carrying VCP, C9orf72 and SOD1 ALS-causing mutations as well as astrocytes stimulated to undergo reactive transformation. Notably, transcripts with decreased IR and increased expression are overrepresented in reactivity processes including cell-adhesion, stress-response, and immune-activation. We examined astrocyte translatome sequencing (TRAP-seq) from a SOD1 mouse model, which revealed a significant number of transcripts with reduced IR in ALS are upregulated in translation. Using nucleo-cytoplasmic fractionation of VCP astrocytes coupled with mRNA sequencing and proteomics, we identify that decreased IR in nuclear-detained transcripts is associated with increased cytoplasmic expression of genes and proteins encoding regulators of reactivity - indicating nuclear-to-cytoplasmic translocation and translation of spliced reactivity-related transcripts. These results provide novel insights into the molecular factors controlling the reactive transformation of ALS astrocytes.

2021-10-25 | GSE160133 | GEO

Transcriptome analysis of senescent and reactive human fetal astrocytes

Project description:Senescence was recently linked to neurodegeneration. Senescent as well as reactive astrocytes were detected in Parkinson’s disease postmortem brains. This study aimed to determine differences and similarities between senescent and reactive astrocytes. Astrocytes were treated with the stressors hydrogen peroxide or rotenone to induce senescence or with the cytokines TNFa+IL1a or with IL1b to induce reactivity in astrocytes. Comparing the transcriptome of senescent and reactive astrocytes revealed a set of genes specific to senescent astrocytes together with genes regulated in a similar way in both astrocyte states.

2021-06-09 | GSE126750 | GEO

Maternal DBP exposure promotes synaptic formation in offspring by activiting astrocytes via AKT/NF-κB/IL-6/JAK2/STAT3 signaling pathway

Project description:In summary, we revealed that maternal DBP exposure activated astrocytes through the AKT/NF-κB/IL-6/JAK2/STAT3 signaling pathway and up-regulated the expression of TSP1, which then affected the density and morphology of dendritic spines and synaptic formation of hippocampal neurons, ultimately leading to decreased autonomy and exploration behavior of offspring.

2023-11-11 | GSE188707 | GEO

Transcriptomic profile of FACS-isolated reactive or SOCS3-deactivated astrocytes from the hippocampus of wildtype and 9-month old APP/PS1dE9 mice

Project description:We analyzed the transcriptional profile of astrocytes from 1) WT mice infected with AAV-GFP, 2) reactive astrocytes from 9-month old APP/PSdE9 mice infected with AAV-GFP and 3) de-activated astrocytes from 9-month old APP/PSdE9 mice infected with AAV-SOCS3 We show SOCS3 normalizes the inflammatory profile of APP astrocytes

2018-09-28 | GSE108520 | GEO

STAT3 labels a subpopulation of reactive astrocytes required for brain metastasis

Project description:The brain microenvironment imposes a particularly intense selective pressure on metastasis initiating cells, but successful metastasis bypass this control through mechanisms that are poorly understood. Reactive astrocytes are key components of this microenvironment, as they have been observed to confine brain metastasis without infiltrating the lesion. We describe a subpopulation of reactive astrocytes surrounding metastatic lesions that are characterized by the activation of STAT3 pathway. Blocking STAT3 signaling in this subpopulation of reactive astrocytes reduces experimental brain metastasis from different primary tumor sources, even at advanced stages of colonization. We conclude that brain metastatic cells induce and maintain the co-option of a pro-metastatic program driven by STAT3 in a subpopulation of reactive astrocytes. We also show that a safe and orally bioavailable treatment that inhibits STAT3 in patients with established brain metastasis and extracranial disease exhibits significant antitumor effects, especially in the CNS where several complete responses were achieved. Given that brain metastasis imposes significant morbidity and mortality, our experimental results suggest a novel treatment for increasing survival in patients with secondary brain tumors.

2018-07-16 | PXD008956 | Pride

Rescuing voluntary motor behavior in a Parkinson´s disease model by aCRISPR mediated reprogramming of striatal astrocytes into induced GABAergic neurons

Project description:Cell replacement strategies of affected cells have been performed in clinical studies of Parkinson´s disease with variable outcome. Conversion of endogenous glial cells into functional neurons might represent a more reliable alternative, thus here we developed a knock-in mouse line carrying a dual dCas9 transactivator system (dCAM), which allowed the conditional activation of the endogenous genes Ascl1, Lmx1a, and Nr4a2 in striatal astrocytes in vivo by delivering sgRNAs specific for their endogenous loci. In order to move this successful approach toward translation, we established an AAV based activator system carrying intein-split-dCas9-VP64, SAM (AAV-dCAS) activators, and the specific sgRNAs targeting transcription factor combinations. Both systems, the dCAM and the AAV-dCAS approach were successful in reprogramming of striatal astrocytes into GABAergic neurons, which functionally integrate into striatal circuits as evidenced by the alleviation of specific motor behaviors in a 6-OHDA Parkinson’s disease model. Thus, the AAV-dCAS approach may enable clinical therapies for Parkinson´s disease by reprogramming striatal astrocytes.

2022-03-15 | GSE149872 | GEO

Proteomic profiling of interferon-responsive reactive astrocytes in rodent and human

Project description:Astrocytes are a heterogenous population of glial cells that respond to pathological insults or injury by undergoing a profound transformation called reactivity. Reactive astrocytes exhibit distinct, context-dependent cellular, molecular, and functional states that can either help or hinder tissue homeostasis. We recently identified a subtype of reactive astrocytes in the mouse brain called interferon-responsive reactive astrocytes (IRRAs), defined by interferon-responsive genes like Igtp, Ifit3, Oasl, Mx1, Cxcl10, and Gbp2 . To further this transcriptomic definition of IRRAs, we wanted to define the proteomic changes that occur in this sub-state.

2023-03-07 | MSV000091426 | MassIVE

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data