Transcriptional Heterogeneity in Naive and Primed Human Pluripotent Stem Cells at Single-Cell Resolution

摘要

Conventional human embryonic stem cells areconsidered to be primed pluripotent but can beinduced to enter a naive state. However, the transcriptionalfeatures associated with naive andprimed pluripotency are still not fully understood.Here we used single-cell RNA sequencing to characterizethe differences between these conditions. Weobserved that both naive and primed populationswere mostly homogeneous with no clear lineagerelatedstructure and identified an intermediate subpopulationof naive cells with primed-like expression.We found that the naive-primed pluripotency axis ispreserved across species, although the timing ofthe transition to a primed state is species specific.We also identified markers for distinguishing humannaive and primed pluripotency as well as strong coregulatoryrelationships between lineage markersand epigenetic regulators that were exclusive tonaive cells. Our data provide valuable insights intothe transcriptional landscape of human pluripotencyat a cellular and genome-wide resolution.