Dataset Information

ScDART-seq reveals distinct m⁶A signatures and mRNA methylation heterogeneity in single cells.

ABSTRACT: N⁶-methyladenosine (m⁶A) is an abundant RNA modification that plays critical roles in RNA regulation and cellular function. Global m⁶A profiling has revealed important aspects of m⁶A distribution and function, but to date such studies have been restricted to large populations of cells. Here, we develop a method to identify m⁶A sites transcriptome-wide in single cells. We uncover surprising heterogeneity in the presence and abundance of m⁶A sites across individual cells and identify differentially methylated mRNAs across the cell cycle. Additionally, we show that cellular subpopulations can be distinguished based on their RNA methylation signatures, independent from gene expression. These studies reveal fundamental features of m⁶A that have been missed by m⁶A profiling of bulk cells and suggest the presence of cell-intrinsic mechanisms for m⁶A deposition.

SUBMITTER: Tegowski M

PROVIDER: S-EPMC8857065 | biostudies-literature | 2022 Feb

REPOSITORIES: biostudies-literature

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scDART-seq reveals distinct m6A signatures and mRNA methylation heterogeneity in single cells.

Tegowski Matthew M Flamand Mathieu N MN Meyer Kate D KD

Molecular cell 20220125 4

N6-methyladenosine (m6A) is an abundant RNA modification that plays critical roles in RNA regulation and cellular function. Global m6A profiling has revealed important aspects of m6A distribution and function, but to date such studies have been restricted to large populations of cells. Here, we develop a method to identify m6A sites transcriptome-wide in single cells. We uncover surprising heterogeneity in the presence and abundance of m<sup ...[more]

PMID: 35081365

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Project description:Rationale: V-domain immunoglobulin suppressor of T cell activation (VISTA) is a novel inhibitory immune checkpoint molecule. Vsir-/- mice have exacerbated psoriasis-like skin inflammation. The immune cell subsets involved in inflammation in Vsir-/- psoriatic mice are largely unknown. We have used scRNA-seq as an unbiased profiling strategy to study the heterogeneity of immune cells at a single cell level in the skin of Vsir-/- psoriatic mice. Methods: In the present study, the right ear and shaved back skin of wild type and Vsir-/- mice were treated with IMQ for 5 consecutive days to induce psoriasis-like dermatitis. Then, the single-cell RNA sequencing analysis of mouse back skin lesions was performed using 10 × Genomics technique. Results: We identified 12 major cell subtypes among 23,258 cells. The major populations of the skin cells included macrophages, dendritic cells and fibroblasts. Macrophages constituted the main immune cell population in the WT (61.29%) and Vsir-/- groups (77.7%). It should be noted that DCs and fibroblasts were expanded in the Vsir-/- psoriatic mice. Furthermore, the gene expression signatures were assessed. We observed that Hspb1 and Cebpb were significantly upregulated in the Vsir-/- psoriatic mice. Differential gene expression and gene ontology enrichment analyses revealed specific gene expression patterns distinguishing these subsets and uncovered putative functions of each cell type. Date analysis resulted in the discovery of a number of novel psoriasis-associated genes in Vsir-/- mice. Conclusion: We present a comprehensive single-cell landscape of the skin immune cells in Vsir-/- psoriatic mice. These unprecedented data uncovered the transcriptional landscape and phenotypic heterogeneity of skin macrophages in psoriasis and identified their gene expression signature suggesting specialized functions in Vsir-/- mice. Our findings will open novel opportunities to investigate the role of VISTA in driving psoriasis.

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ScDART-seq reveals distinct m⁶A signatures and mRNA methylation heterogeneity in single cells.

Publications

scDART-seq reveals distinct m<sup>6</sup>A signatures and mRNA methylation heterogeneity in single cells.

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Dataset Information

ScDART-seq reveals distinct m6A signatures and mRNA methylation heterogeneity in single cells.

Publications

scDART-seq reveals distinct m&lt;sup&gt;6&lt;/sup&gt;A signatures and mRNA methylation heterogeneity in single cells.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

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ScDART-seq reveals distinct m⁶A signatures and mRNA methylation heterogeneity in single cells.

scDART-seq reveals distinct m<sup>6</sup>A signatures and mRNA methylation heterogeneity in single cells.