Molecular mechanisms underlying totipotency

Numerous efforts to understand pluripotency in mammals, using pluripotent stem cells in culture, have enabled the generation of artificially induced pluripotent stem cells, which serve as a valuable source for regenerative medicine and the creation of disease models. In contrast to these tremendous successes in the pluripotency field in the past few decades, our understanding of totipotency, which is highlighted by its broader plasticity than pluripotency, is still limited. This is largely attributable to the scarcity of available materials and the lack of in vitro models. However, recent technological advances have unveiled molecular features that characterize totipotent cells. Single-cell or low-input sequencing technologies allow the dissection of pre- and post-fertilization developmental processes at the molecular level with high resolution. In this review, we describe some of the key findings in understanding totipotency and discuss how totipotency is acquired at the beginning of life.