Analysis of allelic expression patterns in clonal somatic cells by single-cell RNA-seq
Björn Reinius1,2, Jeff E Mold1, Daniel Ramsköld1,2
1Department of Cell and Molecular Biology, Karolinska Institutet, 171 77 Stockholm, Sweden.
Nature Genetics
|September 27, 2016
Summary
Random monoallelic expression (aRME) in somatic cells is mostly dynamic and transient, not clonally inherited. This scattered pattern, observed in mouse and human cells, challenges previous hypotheses about clonal gene expression patches.
Area of Science:
- Genomics
- Cell Biology
- Epigenetics
Background:
- Cellular heterogeneity arises from the expression of single parental alleles.
- The inheritance pattern of random monoallelic expression (aRME) in somatic cells remains debated: whether it's clonal (mitotically inherited) or dynamic (stochastic).
Purpose of the Study:
- To investigate the extent and nature of clonal versus dynamic random monoallelic expression in vivo.
- To differentiate between transient stochastic expression and stable, mitotically inherited allelic silencing.
Main Methods:
- Utilized allele-sensitive single-cell RNA sequencing (scRNA-seq).
- Analyzed clonal primary mouse fibroblasts and human CD8+ T cells.
- Quantified and characterized patterns of monoallelic gene expression.
Main Results:
- Dynamic aRME significantly impacts cell transcriptomes, with levels correlating to transcriptional activity.
- Clonal aRME is rare (<1% of genes), primarily affecting lowly expressed genes.
- The majority of aRME events are transient and stochastic within individual cells.
Conclusions:
- Random monoallelic expression is predominantly a dynamic, transient cellular process.
- Somatic cell populations exhibit scattered aRME patterns, not confined clonal patches.
- Findings challenge the hypothesis of widespread clonal inheritance of monoallelic gene expression.
