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Transcriptome Sequencing Reveals Astrocytes as a Therapeutic Target in Heat-Stroke.

ABSTRACT: Heat-stroke is a serious form of hyperthermia with high mortality, and can induce severe central nervous system disorders. The neurovascular unit (NVU), which consists of vascular cells, glial cells, and neurons, controls blood-brain barrier (BBB) permeability and cerebral blood flow, and maintains the proper functioning of neuronal circuits. However, the detailed function of each BBB component in heat-stroke remains unknown. In order to interpret alterations caused by heat stress, we performed transcriptome comparison of neuron and astrocyte primary cultures after heat treatment. Differentially-expressed genes were then selected and underwent Gene Ontology annotation and Kyoto Encyclopedia of Genes and Genomes pathway analysis. Gene-act networks were also constructed, and the expression of pivotal genes was validated by quantitative PCR, as well as single-cell qPCR in heat-stroke rats. Our work provides valuable information on the transcriptional changes in NVU cells after heat stress, reveals the diverse regulatory mechanisms of two of these cellular components, and shows that a cell-type-specific approach may be a promising therapeutic strategy for heat-stroke treatments.

SUBMITTER: Niu B

PROVIDER: S-EPMC5725376 | biostudies-literature | 2017 Dec

REPOSITORIES: biostudies-literature

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Transcriptome Sequencing Reveals Astrocytes as a Therapeutic Target in Heat-Stroke.

Niu Bing B Zhang Tao T Hu Huaiqiang H Cao Bingzhen B

Neuroscience bulletin 20170711 6

Heat-stroke is a serious form of hyperthermia with high mortality, and can induce severe central nervous system disorders. The neurovascular unit (NVU), which consists of vascular cells, glial cells, and neurons, controls blood-brain barrier (BBB) permeability and cerebral blood flow, and maintains the proper functioning of neuronal circuits. However, the detailed function of each BBB component in heat-stroke remains unknown. In order to interpret alterations caused by heat stress, we performed ...[more]

PMID: 28699024

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Project description:BackgroundThe only therapeutic options that exist for squamous cell lung carcinoma (SCC) are standard radiation and cytotoxic chemotherapy. Cancer stem cells (CSCs) are hypothesized to account for therapeutic resistance, suggesting that CSCs must be specifically targeted. Here, we analyze the transcriptome of CSC and non-CSC subpopulations by RNA-seq to identify new potential therapeutic strategies for SCC.MethodsWe sorted a SCC into CD133- and CD133+ subpopulations and then examined both by copy number analysis (CNA) and whole genome and transcriptome sequencing. We analyzed The Cancer Genome Atlas (TCGA) transcriptome data of 221 SCCs to determine the generality of our observations.ResultsBoth subpopulations highly expressed numerous mRNA isoforms whose protein products are active drug targets for other cancers; 31 (25%) correspond to 18 genes under active investigation as mAb targets and an additional 4 (3%) are of therapeutic interest. Moreover, we found evidence that both subpopulations were proliferatively driven by very high levels of c-Myc and the TRAIL long isoform (TRAILL) and that normal apoptotic responses to high expression of these genes was prevented through high levels of Mcl-1L and Bcl-xL and c-FlipL-isoforms for which drugs are now in clinical development. SCC RNA-seq data (n?=?221) from TCGA supported our findings. Our analysis is inconsistent with the CSC concept that most cells in a cancer have lost their proliferative potential. Furthermore, our study suggests how to target both the CSC and non-CSC subpopulations with one treatment strategy.ConclusionsOur study is relevant to SCC in particular for it presents numerous potential options to standard therapy that target the entire tumor. In so doing, it demonstrates how transcriptome sequencing provides insights into the molecular underpinnings of cancer propagating cells that, importantly, can be leveraged to identify new potential therapeutic options for cancers beyond what is possible with DNA sequencing.

Dataset Information

Transcriptome Sequencing Reveals Astrocytes as a Therapeutic Target in Heat-Stroke.

Publications

Transcriptome Sequencing Reveals Astrocytes as a Therapeutic Target in Heat-Stroke.

Similar Datasets

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