Analysis of allelic expression patterns in clonal somatic cells by single-cell RNA-seq

Nat Genet. 2016 Nov;48(11):1430-1435. doi: 10.1038/ng.3678. Epub 2016 Sep 26.

Abstract

Cellular heterogeneity can emerge from the expression of only one parental allele. However, it has remained controversial whether, or to what degree, random monoallelic expression of autosomal genes (aRME) is mitotically inherited (clonal) or stochastic (dynamic) in somatic cells, particularly in vivo. Here we used allele-sensitive single-cell RNA-seq on clonal primary mouse fibroblasts and freshly isolated human CD8+ T cells to dissect clonal and dynamic monoallelic expression patterns. Dynamic aRME affected a considerable portion of the cells' transcriptomes, with levels dependent on the cells' transcriptional activity. Notably, clonal aRME was detected, but it was surprisingly scarce (<1% of genes) and mainly affected the most weakly expressed genes. Consequently, the overwhelming majority of aRME occurs transiently within individual cells, and patterns of aRME are thus primarily scattered throughout somatic cell populations rather than, as previously hypothesized, confined to patches of clonally related cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alleles*
  • Animals
  • CD8-Positive T-Lymphocytes / metabolism*
  • Cells, Cultured
  • Clone Cells / metabolism
  • Female
  • Fibroblasts / metabolism*
  • Gene Expression Profiling / methods*
  • Humans
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Inbred Strains
  • Polymorphism, Single Nucleotide
  • Sequence Analysis, RNA*