Epigenetic regulator function through mouse gastrulation

Abstract

During ontogeny, proliferating cells become restricted in their fate through the combined action of cell-type specific transcription factors and ubiquitous epigenetic machinery, which index chromatin for activity or repression1,2. Although the molecular functions of these regulators are generally well understood, assigning direct developmental roles is hampered by complex mutant phenotypes that often emerge following gastrulation3. To investigate these phenotypes comprehensively, we generated a panel of ten essential regulators using a combined zygotic perturbation, single-cell RNA sequencing platform where many mutant embryos can be assayed simultaneously to recover robust transcriptional and morphological information. Deeper analysis of central Polycomb Repressive Complex (PRC) 1 and 2 members indicate substantial cooperativity, but distinguishes a PRC2-dominant role in restricting the germline that emerges from gross molecular changes within the initial conceptus. We believe our experimental framework will eventually allow for a fully quantitative view of how cellular diversity emerges using an identical genetic template and from a single totipotent cell.