Feedback control of pluripotency in embryonic stem cells: Signaling, transcription and epigenetics

Abstract

Embryonic stem cells (ESCs) can proliferate and self-renew, maintaining their pluripotency status in vitro for a long period of time. Pluripotent states of ESCs in vitro are supported by a network of signaling, transcriptional and epigenetic regulatory interactions known as the pluripotency gene regulatory network (PGRN). Despite extensive investigation of the network, the exact order of regulatory links and many structural features of the network are still missing. Analysis of published data and literature reveals numerous PGRN components regulating each other in a mutual fashion, thus creating multiple regulatory feedback control circuits. Here we consider possible organizational features of PGRN and describe examples representing known feedback control loops in the context of mouse ESCs. We discuss how the feedback control interactions can contribute to learning behavior and dynamic responses of pluripotency gene network to changing environments. Keywords: Embryonic stem cells, Gene networks, Feedback control, Cellular memory