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Single nucleus RNA Sequencing of nontransgenic and Huntington's disease R6/2 mouse striatum and cortex

ABSTRACT: Single nucleus RNA Sequencing of nontransgenic and Huntington's disease R6/2 mouse striatum and cortex

PROVIDER: PRJNA747702 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR15183173_1.fastq.gz	Fastqsanger.gz
	SRR15183173_2.fastq.gz	Fastqsanger.gz
	SRR15183174_1.fastq.gz	Fastqsanger.gz
	SRR15183174_2.fastq.gz	Fastqsanger.gz
	SRR15183175_1.fastq.gz	Fastqsanger.gz

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Single nucleus RNA Sequencing of nontransgenic and Huntington's disease R6/2 mouse striatum and cortex

Project description:A challenge in treating Huntington's disease (HD) is the complexity of affected brain regions and cell types. We carried out a systematic analysis of cell type-specific changes in cortex and striatum from R6/2 mice at 8 and 12w, and discovered major expression changes in oligodendrocytes (OLs) and oligodendrocyte precursors (OPCs), suggesting that many OLs were arrested in an immature state. Causal gene network analysis implicates PRKCE and SWI/SNF in abnormal OL maturation. PRKCE protein was dramatically decreased. Disrupted cell-to-cell signaling between medium spinyneurons and OL that may contribute to neuronal dysfunction was identified in R6/2 mice using ligand-receptor analysis. These findings reveal novel insights into OL pathology, span multiple brain regions in humans and mice and suggest therapeutic strategies.

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Targeting H3K4 methylation as a therapeutic strategy for Huntington's disease (RNA-seq)

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Project description:Transcriptional dysregulation is an early feature of Huntington's disease (HD). We observed gene-specific changes in H3K4me3 at transcriptionally repressed promoters in R6/2 mouse and human HD brain. Genome-wide analysis showed a novel chromatin signature for this mark. Reducing the levels of the H3K4 demethylase SMCX/Jarid1c in primary neurons reversed down-regulation of key neuronal genes caused by mutant Huntingtin (Htt) expression. Finally, reduction of SMCX/Jarid1c in primary neurons from BACHD mice or the single Jarid1 in a Drosophila HD model was protective. Therefore, targeting this epigenetic signature may be an effective strategy to ameliorate the consequences of HD. ChIP-seq for H3K4me3 in wild type and R6/2 cortex and striatum at 8 and 12 weeks.

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