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Reactive astrocytes promote tumor progression via up-regulating tumor PCDH1 expression in lung cancer brain metastasis

ABSTRACT: Reactive astrocytes promote tumor progression via up-regulating tumor PCDH1 expression in lung cancer brain metastasis

PROVIDER: PRJNA1021583 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR26196604_1.fastq.gz	Fastqsanger.gz
	SRR26196604_2.fastq.gz	Fastqsanger.gz
	SRR26196605_1.fastq.gz	Fastqsanger.gz
	SRR26196605_2.fastq.gz	Fastqsanger.gz
	SRR26196606_1.fastq.gz	Fastqsanger.gz

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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

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

Reactive astrocytes promote tumor progression via up-regulating tumor PCDH1 expression in lung cancer brain metastasis

Project description:To investigate the function of PCDH1 in the lung cancer brain metastasis cells, we established PC9-BrM3 cells in which PCDH1 has been knocked down by shRNA.

2024-02-05 | GSE244170 | GEO

Tumor-associated Reactive Astrocytes Aid the Evolution of Immunosuppressive Environment in Glioblastoma

Project description:Tumor-associated Reactive Astrocytes Aid the Evolution of Immunosuppressive Environment in Glioblastoma

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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

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

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

Exosome-transmitted RVT1 from reactive astrocytes promotes recurrence glioblastoma proliferation

Project description:Glioblastoma (GBM) remains among the most lethal brain tumors despite improvements in treatment. Surgical resection is a universal component of glioma therapy. However, the mechanism underlying postoperative recurrence remains a challenge due to limited information regarding the changes that occur in the postoperative microenvironment. Here, we show that a subtype of proinflammatory reactive astrocytes designated is induced by inflammatory cytokines or injury. We show that reactive astrocytes can secrete the long noncoding RNA (lncRNA) LOC646762 to promotes recurrence glioblastoma proliferation in an exosome-dependent manner.We firstly named this reactive astrocyte associated lnRNA as “lnc-RVT1”.

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

Project description: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

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