The interface between pluripotency and lineage commitment (360G-Wellcome-317944_Z_24_Z)

Pluripotent cells can differentiate into all cell types. An essential feature of these cells in vivo is their ability to maintain the correct balance between self-renewal and differentiation. Therefore, understanding the mechanisms that control their decision-making is important. Pluripotent cells have been best studied in mammals. However, given their transient nature in these animals–existing only in early embryos–mammalian pluripotency research has been restricted to in vitro systems that do not fully recapitulate the behavior of cells in vivo. I propose to study pluripotency in the cnidarian Hydractinia symbiolongicarpus. This animal, a close relative of jellyfish, possesses adult pluripotent stem cells (known as i-cells) and can also reprogram somatic cells. It provides continuous access to pluripotent stem cells and to all stages of differentiation and reprogramming in a single, genetically tractable biological system. This research will address, at single-cell resolution, the fine steps i-cells make as they lose and regain pluripotency, focusing on the transcriptome and chromatin structure that control them and providing mechanistic insight into the role of pluripotency transcription factors in mediating cell fate. A non-mammalian pluripotency system can provide a different perspective for understanding core pluripotency mechanisms and inspire the design of new reprogramming strategies.