Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Single Cell Multiomics Across Nine Mammals Reveals Cell Type Specific Regulatory Conservation in the Brain [MPRA]

ABSTRACT: Here, we generated a multiomic data from post-mortem cortex tissue across nine mammals and identified candidate CREs (cCREs) in a cell type–specific manner. We developed a multidimensional framework of conservation, integrating sequence, chromatin accessibility, and enhancer–gene linkage. Using massively parallel reporter assays (MPRA) in human neural progenitor cells and neurons, we measured activity of cCREs spanning conserved to human-specific regions. CRISPR interference (CRISPRi) validated conserved enhancer function, including at neurodevelopmental loci like FAM181B. Motif enrichment and chromBPnet revealed transcription factors distinguishing conserved versus recent cCREs. Linkage disequilibrium score regression showed both conserved and human-specific cCREs were enriched for neuropsychiatric GWAS risk, while neurodegenerative risk was confined to conserved elements. Our findings define functional dimensions of enhancer conservation and demonstrate how regulatory evolution shapes human brain biology and disease susceptibility.

ORGANISM(S): Homo sapiens

PROVIDER: GSE303114 | GEO | 2025/08/07

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Single Cell Multiomics Across Nine Mammals Reveals Cell Type Specific Regulatory Conservation in the Brain

Project description:Here, we generated a multiomic data from post-mortem cortex tissue across nine mammals and identified candidate CREs (cCREs) in a cell type–specific manner. We developed a multidimensional framework of conservation, integrating sequence, chromatin accessibility, and enhancer–gene linkage. Using massively parallel reporter assays (MPRA) in human neural progenitor cells and neurons, we measured activity of cCREs spanning conserved to human-specific regions. CRISPR interference (CRISPRi) validated conserved enhancer function, including at neurodevelopmental loci like FAM181B. Motif enrichment and chromBPnet revealed transcription factors distinguishing conserved versus recent cCREs. Linkage disequilibrium score regression showed both conserved and human-specific cCREs were enriched for neuropsychiatric GWAS risk, while neurodegenerative risk was confined to conserved elements. Our findings define functional dimensions of enhancer conservation and demonstrate how regulatory evolution shapes human brain biology and disease susceptibility.

2025-08-07 | GSE303045 | GEO

Single Cell Multiomics Across Nine Mammals Reveals Cell Type Specific Regulatory Conservation in the Brain [Multiome]

2025-08-07 | GSE303115 | GEO

Single Cell Multiomics Across Nine Mammals Reveals Cell Type Specific Regulatory Conservation in the Brain [RNA-Seq]

2025-08-07 | GSE303113 | GEO

Single Cell Multiomics Across Nine Mammals Reveals Cell Type Specific Regulatory Conservation in the Brain [ATAC-seq]

2025-08-07 | GSE303046 | GEO

Interpreting type 1 diabetes risk with genetics and single cell epigenomics

Project description:Genetic risk variants identified in genome-wide association studies (GWAS) of complex disease are primarily non-coding, and translating risk variants into mechanistic insight requires detailed gene regulatory maps in disease-relevant cell types. Here, we combined a GWAS of type 1 diabetes (T1D) in 520,580 samples with candidate cis-regulatory elements (cCREs) in pancreas and peripheral blood mononuclear cell types defined using single nucleus ATAC-seq (snATAC-seq) of 131,554 nuclei. T1D risk variants were enriched in cCREs active in T cells and additional cell types, including acinar and ductal cells of the exocrine pancreas. Risk variants at multiple T1D signals overlapped exocrine-specific cCREs linked to genes with exocrine-specific expression. At the CFTR locus, T1D risk variant rs7795896 mapped in a ductal-specific cCRE which regulated CFTR, and the risk allele reduced transcription factor binding, enhancer activity and CFTR expression in ductal cells. These findings support a role for the exocrine pancreas in T1D pathogenesis and highlight the power of large-scale GWAS and single cell epigenomics for understanding the cellular origins of complex disease.

2021-03-15 | GSE163160 | GEO

A comparative atlas of single-cell chromatin accessibility in the human brain

Project description:A comparative atlas of single-cell chromatin accessibility in the human brainRecent advances in single-cell transcriptomics have illuminated the diverse neuronal and glial cell types within the human brain. However, the regulatory programs governing cell identity and function remain unclear. Using a single-nucleus assay for transposase-accessible chromatin using sequencing (ATAC-seq), we explored open chromatin landscapes across 1.1 million cells in 42 brain regions from three adults. Integrating this data unveiled 107 distinct cell types and their specific utilization of 544,735 candidate cis-regulatory DNA elements (cCREs) in the human genome. Nearly a third of the cCREs demonstrated conservation and chromatin accessibility in the mouse brain cells. We reveal strong links between specific brain cell types and neuropsychiatric disorders including schizophrenia, bipolar disorder, Alzheimer’s disease (AD), and major depression, and have developed deep learning models to predict the regulatory roles of noncoding risk variants in these disorders.

2023-10-04 | GSE244618 | GEO

Comparative single cell epigenomic analysis of gene regulatory programs in the rodent and primate motor cortex [Macaque]

Project description:Sequence divergence of cis-regulatory elements drives species-specific traits, but how this manifests in the evolution of the neocortex at the molecular and cellular level remains to be elucidated. We investigated the gene regulatory programs in the primary motor cortex of human, macaque, marmoset, and mouse with single-cell multiomics assays, generating gene expression, chromatin accessibility, DNA methylome, and chromosomal conformation profiles from a total of over 180,000 cells. For each modality, we determined species-specific, divergent, and conserved gene expression and epigenetic features at multiple levels. We find that cell type-specific gene expression evolves more rapidly than broadly expressed genes and that epigenetic status at distal candidate cis-regulatory elements (cCREs) evolves faster than promoters. Strikingly, transposable elements (TEs) contribute to nearly 80% of the human-specific cCREs in cortical cells. Through machine learning, we develop sequence-based predictors of cCREs in different species and demonstrate that the genomic regulatory syntax is highly preserved from rodents to primates. Lastly, we show that epigenetic conservation combined with sequence similarity helps uncover functional cis-regulatory elements and enhances our ability to interpret genetic variants contributing to neurological disease and traits.

2023-10-31 | GSE240297 | GEO

Comparative single cell epigenomic analysis of gene regulatory programs in the rodent and primate motor cortex [H3K27ac]

Project description:Sequence divergence of cis-regulatory elements drives species-specific traits, but how this manifests in the evolution of neocortex at the molecular and cellular level remains to be elucidated. We investigated the gene regulatory programs in the primary motor cortex of human, macaque, marmoset, and mouse with single cell multiomics assays, generating gene expression, chromatin accessibility, DNA methylome and chromosomal conformation profiles from a total of over 180,000 cells. For each modality, we determined species-specific, divergent, and conserved gene expression and epigenetic features at multiple levels. We find that cell type-specific gene expression evolves more rapidly than broadly expressed genes, and that epigenetic status at distal candidate cis-regulatory elements (cCREs) evolves faster than promoters. Strikingly, transposable elements (TEs) contribute to nearly 80% of the human-specific cCREs in cortical cells. Through machine learning, we develop sequence-based predictors of cCREs in different species, and demonstrate that the genomic regulatory syntax is highly preserved from rodents to primates. Lastly, we show that epigenetic conservation combined with sequence similarity help uncover functional cis-regulatory elements and enhance our ability to interpret genetic variants contributing to neurological disease and traits.

2023-11-28 | GSE246760 | GEO

Comparative single cell epigenomic analysis of gene regulatory programs in the rodent and primate motor cortex [marmoset]

2023-11-15 | GSE241339 | GEO

Comparative single cell epigenomic analysis of gene regulatory programs in the rodent and primate motor cortex

2023-10-31 | GSE229169 | GEO