Single-Cell RNA-Seq Reveals Dynamic, Random Monoallelic Gene Expression in Mammalian Cells

TLDR

Expression from both alleles is generally observed in analyses of diploid cell populations, but genome‑wide single‑cell studies of allelic expression are lacking. The study aims to globally analyze allelic expression in individual mouse preimplantation embryos. The authors performed single‑cell RNA‑seq on embryos from a CAST/EiJ × C57BL/6J cross. They found abundant (12–24%) monoallelic expression of autosomal genes, with independent and stochastic transcription producing random, dynamic monoallelic patterns in related embryonic cells, similar patterns in mature cells, and de novo paternal X‑chromosome inactivation, demonstrating that stochastic allelic transcription generates widespread random monoallelic expression in mammalian cells.

Abstract

Expression from both alleles is generally observed in analyses of diploid cell populations, but studies addressing allelic expression patterns genome-wide in single cells are lacking. Here, we present global analyses of allelic expression across individual cells of mouse preimplantation embryos of mixed background (CAST/EiJ × C57BL/6J). We discovered abundant (12 to 24%) monoallelic expression of autosomal genes and that expression of the two alleles occurs independently. The monoallelic expression appeared random and dynamic because there was considerable variation among closely related embryonic cells. Similar patterns of monoallelic expression were observed in mature cells. Our allelic expression analysis also demonstrates the de novo inactivation of the paternal X chromosome. We conclude that independent and stochastic allelic transcription generates abundant random monoallelic expression in the mammalian cell.