Abstract
Stochastic and deterministic allele specific gene expression (ASE) might influence single cell phenotype, but the extent and nature of the phenomenon at the onset of early mouse development is unknown. Here we performed single cell RNA-Seq analysis of single blastomeres of mouse embryos, which revealed significant changes in the transcriptome. Importantly, over half of the transcripts with detectable genetic polymorphisms exhibit ASE, most notably, individual blastomeres from the same two-cell embryo show similar pattern of ASE. However, about 6% of them exhibit stochastic expression, indicated by altered expression ratio between the two alleles. Thus, we demonstrate that ASE is both deterministic and stochastic in early blastomeres. Furthermore, we also found that 1,718 genes express two isoforms with different lengths of 3′UTRs, with the shorter one on average 5–6 times more abundant in early blastomeres compared to the transcripts in epiblast cells, suggesting that microRNA mediated regulation of gene expression acquires increasing importance as development progresses.
Highlights
Preimplantation development from the totipotent zygote to the blastocyst culminates in the establishment of pluripotent inner cell mass cells (ICM) and trophectoderm cells at embryonic day (E) 3.5 [1]
Using principal component analysis (PCA), we found individual cells to be clustered at each development stage, and the relative distances between each stage represent the extent of change in the transcriptome (Fig. 1)
We found that 2,193 transcripts were upregulated and 8,173 transcripts downregulated when comparing oocyte with blastomeres from two-cell stage embryos, a change by approximately 70% of all expressed genes
Summary
Preimplantation development from the totipotent zygote to the blastocyst culminates in the establishment of pluripotent inner cell mass cells (ICM) and trophectoderm cells at embryonic day (E) 3.5 [1]. Differential gene expression in individual cells is a key determinant of cellular differentiation, functions and physiology [2,3]. This includes allele specific expression (ASE) or differential allelic expression (DAE), which in some instances is due to parent of origin specific imprinting that affects X inactivation. A subtle change in gene expression, as in the case of tumor suppressor gene, Pten, is sufficient for a profound effect on cell susceptibility phenotype in mice [8]. ASE has not been investigated during early development due to the limited amount of material available for analysis.
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