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Neagu, A.* ; van Genderen, E.* ; Escudero, I.* ; Verwegen, L.* ; Kurek, D.* ; Lehmann, J.* ; Stel, J.* ; Dirks, R.A.M.* ; van Mierlo, G.* ; Maas, A.* ; Eleveld, C.* ; Ge, Y.* ; den Dekker, A.T.* ; Brouwer, R.W.W.* ; van IJcken, W.F.J.* ; Modic, M.* ; Drukker, M. ; Jansen, J.H.* ; Rivron, N.C.* ; Baart, E.B.* ; Marks, H.* ; ten Berge, D.*

In vitro capture and characterization of embryonic rosette-stage pluripotency between naive and primed states.

Nat. Cell Biol. 22, 534-545 (2020)
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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. We identify here a rosette pluripotent state defined 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 progression to primed pluripotency. Consequently, combined WNT and MEK inhibition supports rosette-like stem cells, a self-renewing naive-primed intermediate. Rosette-like stem cells erase constitutive heterochromatin marks and display a primed chromatin landscape, with bivalently marked primed pluripotency genes. Nonetheless, WNT induces reversion to naive pluripotency. 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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Publication type Article: Journal article
Document type Scientific Article
Keywords Germ-cell Specification; Epiblast Stem-cells; Ground-state; Dna Methylation; Genome-wide; Mouse Blastocysts; Axis Formation; Wnt Proteins; Chromatin; Transition
ISSN (print) / ISBN 1465-7392
e-ISSN 1476-4679
Quellenangaben Volume: 22, Issue: 5, Pages: 534-545 Article Number: , Supplement: ,
Publisher Nature Publishing Group
Publishing Place Macmillan Building, 4 Crinan St, London N1 9xw, England
Reviewing status Peer reviewed