Inducible cell-specific mouse models for paired epigenetic and transcriptomic studies of microglia and astroglia.

Communications Biology
Ana J Chucair-ElliottWillard M Freeman

Abstract

Epigenetic regulation of gene expression occurs in a cell type-specific manner. Current cell-type specific neuroepigenetic studies rely on cell sorting methods that can alter cell phenotype and introduce potential confounds. Here we demonstrate and validate a Nuclear Tagging and Translating Ribosome Affinity Purification (NuTRAP) approach for temporally controlled labeling and isolation of ribosomes and nuclei, and thus RNA and DNA, from specific central nervous system cell types. Analysis of gene expression and DNA modifications in astrocytes or microglia from the same animal demonstrates differential usage of DNA methylation and hydroxymethylation in CpG and non-CpG contexts that corresponds to cell type-specific gene expression. Application of this approach in LPS treated mice uncovers microglia-specific transcriptome and epigenome changes in inflammatory pathways that cannot be detected with tissue-level analysis. The NuTRAP model and the validation approaches presented can be applied to any brain cell type for which a cell type-specific cre is available.

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Citations

Jan 1, 2021·Mechanisms of Ageing and Development·Victor A AnsereWillard M Freeman
Aug 15, 2021·Neuron·Anaelle Aurelie DumasMarco Prinz

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Datasets Mentioned

BETA
GSE140271
GSE140974
GSE84540
GSE114001

Methods Mentioned

BETA
transgenic
flow cytometry
confocal microscopy
Amplicon Sequencing
PCA
dissections
RNAseq
TRAP-RNAseq
affinity purification
genotyping

Software Mentioned

GraphPad Prism
Bowtie
NuTRAP
R package Enriched Heatmap
CLC Genomics Workbench
Adobe Photoshop
UCSC Genome Browser Table Browser
R
Bismark
CEGX QC

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