Frontiers of pluripotency

Abstract

Humans develop from a unique group of pluripotent cells in early embryos that can produce all cells of the human body. While pluripotency is only transiently manifest in the embryo, scientists have identified conditions that sustain pluripotency indefinitely in the laboratory. Pluripotency is not a monolithic entity, however, but rather comprises a spectrum of different cellular states. Questions regarding the scientific value of examining the continuum of pluripotent stem (PS) cell states have gained increased significance in light of attempts to generate interspecies chimeras between humans and animals. In this chapter, I review our ever-evolving understanding of the continuum of pluripotency. Historically, the discovery of two different PS cell states in mice fostered a general conception of pluripotency comprised of two distinct attractor states: Naïve and primed. Naïve pluripotency has been defined by competence to form germline chimeras and governance by unique KLF-based transcription factor (TF) circuitry, whereas primed state is distinguished by an inability to generate chimeras and alternative TF regulation. However, the discovery of many alternative PS cell states challenges the concept of pluripotency as a binary property. Moreover, it remains unclear whether the current molecular criteria used to classify human naïve-like pluripotency also identify human chimera-competent PS cells. Therefore, I examine the pluripotency continuum more closely in light of recent advances in PS cell research and human interspecies chimera research.