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Single-Cell Transcriptomics Analyses of Neural Stem Cell Heterogeneity and Contextual Plasticity in a Zebrafish Brain Model of Amyloid Toxicity.

Cell reports | 2019

The neural stem cell (NSC) reservoir can be harnessed for stem cell-based regenerative therapies. Zebrafish remarkably regenerate their brain by inducing NSC plasticity in a Amyloid-β-42 (Aβ42)-induced experimental Alzheimer's disease (AD) model. Interleukin-4 (IL-4) is also critical for AD-induced NSC proliferation. However, the mechanisms of this response have remained unknown. Using single-cell transcriptomics in the adult zebrafish brain, we identify distinct subtypes of NSCs and neurons and differentially regulated pathways and their gene ontologies and investigate how cell-cell communication is altered through ligand-receptor pairs in AD conditions. Our results propose the existence of heterogeneous and spatially organized stem cell populations that react distinctly to amyloid toxicity. This resource article provides an extensive database for the molecular basis of NSC plasticity in the AD model of the adult zebrafish brain. Further analyses of stem cell heterogeneity and neuro-regenerative ability at single-cell resolution could yield drug targets for mobilizing NSCs for endogenous neuro-regeneration in humans.

Pubmed ID: 31018142 RIS Download

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This is a list of tools and resources that we have found mentioned in this publication.


S100 (antibody)

RRID:AB_10013383

This polyclonal targets S100 isolated from cow brain.

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Anti-GFP antibody (antibody)

RRID:AB_300798

This polyclonal targets GFP

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SourceForge (software resource)

RRID:SCR_004365

Web based service that offers software developers centralized online location to control and manage free and open source software projects. Open source software tool and business public software platform.

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tenx (production service resource)

RRID:SCR_016957

Pipeline for the analysis of 10x single cell RNA sequencing data. Collection of python3 pipelines and Rscripts to analyze data generated with the 10x Genomics platform. The pipelines are based on 10x's Cell Ranger pipeline for mapping and quantitation and the R Seurat package for downstream analysis.

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R Project for Statistical Computing (software resource)

RRID:SCR_001905

Software environment and programming language for statistical computing and graphics. R is integrated suite of software facilities for data manipulation, calculation and graphical display. Can be extended via packages. Some packages are supplied with the R distribution and more are available through CRAN family.It compiles and runs on wide variety of UNIX platforms, Windows and MacOS.

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GOstat (service resource)

RRID:SCR_008535

GOstat is a tool that allows you to find statistically overrepresented Gene Ontologies within a group of genes. The Gene-Ontology database (GO: http://www.geneontology.org) provides a useful tool to annotate and analyze the function of large numbers of genes. Modern experimental techniques, as e.g. DNA microarrays, often result in long lists of genes. To learn about the biology in this kind of data it is desirable to find functional annotation or Gene-Ontology groups which are highly represented in the data. This program (GOstat) should help in the analysis of such lists and will provide statistics about the GO terms contained in the data and sort the GO annotations giving the most representative GO terms first. Run GOstat: * Go to search form - Computes GO statistics of a list of genes selected from a microarray. * GOstat Display - You can store results from a previously run and view them here, either by uploading them as a file or putting them on a selected URL. * Upload Custom GO Annotations - This allows you to upload your own GO annotation database and use it with GOstat. Variants of GOstat: * Rank GOstat - Takes input from all genes on microarray instead of using a fixed cutoff and uses ranks using a Wilcoxon test or either ranks or pvalues to score GOs using Kolmogorov-Smirnov statistics. * Gene Abundance GOstats - Takes input from all genes on microarray and sums up the gene abundances for each GO to compute statistics. * Two list GOstat - Compares GO statistics in two independent lists of genes, not necessarily one of them being the complete list the other list is sampled from. Platform: Online tool

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Seurat (software resource)

RRID:SCR_016341

Software as R package designed for QC, analysis, and exploration of single cell RNA-seq data. Enable users to identify and interpret sources of heterogeneity from single cell transcriptomic measurements, and to integrate diverse types of single cell data.

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S100 (antibody)

RRID:AB_10013383

This polyclonal targets S100 isolated from cow brain.

View all literature mentions