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Human and rat skeletal muscle single-nuclei multi-omic integrative analyses nominate causal cell types, regulatory elements, and SNPs for complex traits [snATAC-seq]

ABSTRACT: Human and rat skeletal muscle single-nuclei multi-omic integrative analyses nominate causal cell types, regulatory elements, and SNPs for complex traits [snATAC-seq]

PROVIDER: PRJNA740260 | ENA |

REPOSITORIES: ENA

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Human and rat skeletal muscle single-nuclei multi-omic integrative analyses nominate causal cell types, regulatory elements, and SNPs for complex traits [snATAC-seq]

Project description:Skeletal muscle accounts for the largest proportion of human body mass, on average, and is a key tissue in complex diseases and mobility. It is composed of several different cell and muscle fiber types. Here, we optimize single-nucleus ATAC-seq (snATAC-seq) to map skeletal muscle cell-specific chromatin accessibility landscapes in frozen human and rat samples, and single-nucleus RNA-seq (snRNA-seq) to map cell-specific transcriptomes in human. We additionally perform multi-omics profiling (gene expression and chromatin accessibility) on human and rat muscle samples. We capture type I and type II muscle fiber signatures, which are generally missed by existing single-cell RNA-seq methods. We perform cross-modality and cross-species integrative analyses on 33,862 nuclei and identify seven cell types ranging in abundance from 59.6% to 1.0% of all nuclei. We introduce a regression-based approach to infer cell types by comparing transcription start site-distal ATAC-seq peaks to reference enhancer maps and show consistency with RNA-based marker gene cell type assignments. We find heterogeneity in enrichment of genetic variants linked to complex phenotypes from the UK Biobank and diabetes genome wide association studies in cell-specific ATAC-seq peaks, with the most striking enrichment patterns in muscle mesenchymal stem cells (~3.5% of nuclei). Finally, we overlay these chromatin accessibility maps on GWAS data to nominate causal cell types, SNPs, transcription factor motifs, and target genes for type 2 diabetes signals. These chromatin accessibility profiles for human and rat skeletal muscle cell types are a useful resource for nominating causal GWAS SNPs and cell types.

2021-06-23 | GSE178733 | GEO

Human and rat skeletal muscle single-nuclei multi-omic integrative analyses nominate causal cell types, regulatory elements, and SNPs for complex traits [snRNA-seq]

2021-06-23 | GSE178734 | GEO

Human and rat skeletal muscle single-nuclei multi-omic integrative analyses nominate causal cell types, regulatory elements, and SNPs for complex traits

Project description:Human and rat skeletal muscle single-nuclei multi-omic integrative analyses nominate causal cell types, regulatory elements, and SNPs for complex traits

| PRJNA740255 | ENA

Human and rat skeletal muscle single-nuclei multi-omic integrative analyses nominate causal cell types, regulatory elements, and SNPs for complex traits [snRNA-seq]

Project description:Human and rat skeletal muscle single-nuclei multi-omic integrative analyses nominate causal cell types, regulatory elements, and SNPs for complex traits [snRNA-seq]

| PRJNA740261 | ENA

snATAC-seq of the developing mouse cerebellum across eleven stages

Project description:This study used droplet-based snATAC-seq to profile the chromatin accessibility landscape of 91,922 nuclei in the mouse cerebellum across eleven developmental stages, from the beginning of neurogenesis (e10.5) till adulthood (P63). The study included two biological replicates per stage, one from each sex. Cerebelli were dissected as whole or in two halves, nuclei were extracted and profiled using 10x single-cell ATAC reagent kit (v1.0) and a Chromium controller. Libraries were sequenced using paired-reads on Illumina NextSeq 550 and initial data processing was performed using Cellranger ATAC (1.1).

2021-09-07 | E-MTAB-9765 | biostudies-arrayexpress

Human and rat skeletal muscle single-nuclei multi-omic integrative analyses nominate causal cell types, regulatory elements, and SNPs for complex traits

Project description:This SuperSeries is composed of the SubSeries listed below.

2021-06-23 | GSE178735 | GEO

snATAC-seq of the gray short-tailed opossum cerebellum in two developmental stages

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A Dinucleotide-barcode reporter system and application in dissecting the causal rule of regulatory risk SNPs

Project description:We adapted the DiR barcode-based parallel reporter assay systems strategy to systematically identify the SNPs that affect gene expression by modulating activities of regulatory elements. Among 293 SNPs linked with GWAS-identified prostate cancer-risk SNPs, we found 32, 9, and 11 regulatory SNPs in 22Rv1, PC-3, and LNCaP cells. Further mechanism study indicates that one SNP regulates gene expression in prostate cancer malignancy. The DiR system has great potential to advance the functional study of risk SNPs that have associations with polygenic diseases. Our findings hold great promise in benefiting prostate cancer patients with prognostic prediction.

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Project description:Multi-omic profiling of single nuclei uncovers regulatory diversity of brain cell types and diseases

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2024-05-27 | GSE243868 | GEO

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