Expression profiling by high throughput sequencing Methylation profiling by high throughput sequencing
Summary
Embryonic stem cells (ESC) are characterised by the pluripotent capacity to generate all embryonic lineages. Here we show ESC can occupy a spectrum of distinct transcriptional and epigenetic states in response to varied extrinsic conditions. This spectrum broadly corresponds to a developmental continuum of pluripotency and is coupled with a gradient of increasing global DNA methylation. Each pluripotent state is linked with activation of distinct classes of transposable elements (TE), which in turn influence ESC through generating chimeric transcripts. Moreover, varied ESC culture parameters differentially license activation of master lineage-regulators, including Sox1, Gata4 or Blimp1, and influence differentiation. The activation of Blimp1 is prevalent in 2i (without-LIF) conditions, and marks a dynamic primordial germ cell (PGC)-like sub-state, that is directly repressed by Klf4 downstream of LIF/STAT3 signalling. Thus, extrinsic cues establish a spectrum of pluripotent states, in part by modulating sub-populations, as well as directing the transcriptome, epigenome, and TE.
Overall design
Replicate RNA-seq and Methyl-seq datasets from mESC (129 or B6 background), maintained in multiple pluripotent culture parameters.
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