Dynamic transcriptional symmetry-breaking in pre-implantation mammalian embryo development revealed by single-cell RNA-seq

Abstract

During mammalian preimplantation embryo development, when the first asymmetry emerges and how it develops to direct distinct cell fates remain longstanding questions. Here, by analyzing single-blastomere transcriptome data from mouse and human pre-implantation embryos, we revealed that the initial blastomere-to-blastomere biases emerge as early as the first embryonic cleavage division, following a binominal distribution pattern. The following zygotic transcriptional activation further elevated overall blastomere-to-blastomere biases during 2- to 16-cell embryo stages, whereas the trends of transcriptional asymmetry fall into two distinct patterns: some genes tends to minimize the extent of asymmetry between blastomeres (monostable pattern); while other genes, including those known lineage specifiers, showed ever-increasing asymmetry between blastomeres (bistable pattern), supposedly controlled by negative or positive feedbacks. Moreover, our analysis supports a scenario that opposing lineage specifiers within an early blastomere constantly compete with each other based on their relative ratio, forming a inclined “lineage strength” that push the blastomere onto predisposed, yet flexible lineage track before morphological distinction.