Following implantation, the naive pluripotent epiblast of the mouse blastocyst generates a rosette, undergoes lumenogenesis and forms the primed pluripotent egg cylinder, which is able to generate the embryonic tissues. How pluripotency progression and morphogenesis are linked and whether intermediate pluripotent states exist remain controversial.
In a joined effort led by the Derk ten Berge group of ErasmusMC, the team of Hendrik Marks, theme Cancer development and immune defense, identified an exciting new "rosette" state of pluripotency as reported in Nature Cell Biology. See here for a preview in Nature Cell Biology putting these findings in perspective.
The rosette pluripotent state is characterized by the co-expression of naive factors with the transcription factor OTX2. Downregulation of blastocyst WNT signals drives the transition into rosette pluripotency by inducing OTX2. The rosette then activates MEK signals that induce lumenogenesis and drive further developmental progression. Importantly, the combined WNT and MEK inhibition now supports derivation of in vitro rosette-like stem cells, a self-renewing naive-primed intermediate. Altogether, the rosette is therefore a reversible pluripotent intermediate whereby control over both pluripotency progression and morphogenesis pivots from WNT to MEK signals.
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