Charting Developmental Dissolution of Pluripotency

•Developmental potency of the naïve pre-implantation epiblast is captured in ESCs.•ESC pluripotency is maintained by a specific transcription factor network.•Developmental progression is genetically hardwired into the ESC circuitry, and inhibition of differentiation programs is required for the stabilization of pluripotency in vitro.•Parallel and sequential mechanisms safeguard the orderly disassembly of naïve pluripotency and transition into a cell state poised for immediate lineage induction.

The formation of tissues and organs during metazoan development begs fundamental questions of cellular plasticity: How can the very same genome program have diverse cell types? How do cell identity programs unfold during development in space and time? How can defects in these mechanisms cause disease and also provide opportunities for therapeutic intervention? And ultimately, can developmental programs be exploited for bioengineering tissues and organs? Understanding principle designs of cellular identity and developmental progression is crucial for providing answers. Here, I will discuss how the capture of embryonic pluripotency in murine embryonic stem cells (ESCs) in vitro has allowed fundamental insights into the molecular underpinnings of a developmental cell state and how its ordered disassembly during differentiation prepares for lineage specification.

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