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Single nucleus multiomics identifies ZEB1 and MAFB as candidate regulators of Alzheimer’s disease-specific cis regulatory elements [Multi-omics]

ABSTRACT: Single nucleus multiomics identifies ZEB1 and MAFB as candidate regulators of Alzheimer’s disease-specific cis regulatory elements [Multi-omics]

PROVIDER: PRJNA887819 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR21834805.fastq.gz	Fastqsanger.gz
	SRR21834806.fastq.gz	Fastqsanger.gz
	SRR21834807.fastq.gz	Fastqsanger.gz
	SRR21834808.fastq.gz	Fastqsanger.gz
	SRR21834809.fastq.gz	Fastqsanger.gz

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Single nucleus multiomics identifies ZEB1 and MAFB as candidate regulators of Alzheimer’s disease-specific cis regulatory elements [Multi-omics]

Project description:Cell type-specific transcriptional differences between brain tissues from donors with Alzheimer’s Disease (AD) and unaffected controls have been well-documented, but few studies have rigorously interrogated the regulatory mechanisms responsible for these alterations. We performed single nucleus multiomics (snRNA-seq + snATAC-seq) on 105,332 nuclei isolated from cortical tissues from 7 AD and 8 unaffected donors to identify candidate cis-regulatory elements (CREs) involved in AD-associated transcriptional changes. We detected 319,861 significant correlations, or links, between gene expression and cell-type specific transposase accessible regions that are enriched for active CREs. Among these, 40,831 were unique to AD tissues. Validation experiments confirmed the activity of many regions, including several candidate regulators of APP expression. We identified ZEB1 and MAFB as transcription factors playing important roles in AD-specific gene regulation in neurons and microglia, respe ctively. Microglial links were globally enriched for heritability of AD risk and previously identified active regulatory regions.

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Project description:Cell type-specific transcriptional differences between brain tissues from donors with Alzheimer’s Disease (AD) and unaffected controls have been well-documented, but few studies have rigorously interrogated the regulatory mechanisms responsible for these alterations. We performed single nucleus multiomics (snRNA-seq + snATAC-seq) on 105,332 nuclei isolated from cortical tissues from 7 AD and 8 unaffected donors to identify candidate cis-regulatory elements (CREs) involved in AD-associated transcriptional changes. We detected 319,861 significant correlations, or links, between gene expression and cell-type specific transposase accessible regions that are enriched for active CREs. Among these, 40,831 were unique to AD tissues. Validation experiments confirmed the activity of many regions, including several candidate regulators of APP expression. We identified ZEB1 and MAFB as transcription factors playing important roles in AD-specific gene regulation in neurons and microglia, respectively. Microglial links were globally enriched for heritability of AD risk and previously identified active regulatory regions.

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Single nucleus multiomics identifies ZEB1 and MAFB as candidate regulators of Alzheimer′s disease-specific cis regulatory elements [ChIP-seq]

Project description:Cell type-specific transcriptional differences between brain tissues from donors with Alzheimer’s Disease (AD) and unaffected controls have been well-documented, but few studies have rigorously interrogated the regulatory mechanisms responsible for these alterations. We performed single nucleus multiomics (snRNA-seq + snATAC-seq) on 105,332 nuclei isolated from cortical tissues from 7 AD and 8 unaffected donors to identify candidate cis-regulatory elements (CREs) involved in AD-associated transcriptional changes. We detected 319,861 significant correlations, or links, between gene expression and cell-type specific transposase accessible regions that are enriched for active CREs. Among these, 40,831 were unique to AD tissues. Validation experiments confirmed the activity of many regions, including several candidate regulators of APP expression. We identified ZEB1 and MAFB as transcription factors playing important roles in AD-specific gene regulation in neurons and microglia, respectively. Microglial links were globally enriched for heritability of AD risk and previously identified active regulatory regions.

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Single nucleus multiomics identifies ZEB1 and MAFB as candidate regulators of Alzheimer′s disease-specific cis regulatory elements

Project description:Single nucleus multiomics identifies ZEB1 and MAFB as candidate regulators of Alzheimer′s disease-specific cis regulatory elements

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Single nucleus multiomics identifies ZEB1 and MAFB as candidate regulators of Alzheimer′s disease-specific cis regulatory elements [ChIP-seq]

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