title: Canonical Wnt signaling induces a primitive endoderm metastable state in mouse embryonic stem cells.
abstract: Activation of the canonical Wnt signaling pathway synergizes with leukemia inhibitory factor (LIF) to maintain pluripotency of mouse embryonic stem cells (mESCs). However, in the absence of LIF, Wnt signaling is unable to maintain ESCs in the undifferentiated state. To investigate the role of canonical Wnt signaling in pluripotency and lineage specification, we expressed Wnt3a in mESCs and characterized them in growth and differentiation. We found that activated canonical Wnt signaling induced the formation of a reversible metastable primitive endoderm state in mESC. Upon subsequent differentiation, Wnt3a-stimulated mESCs gave rise to large quantities of visceral endoderm. Furthermore, we determined that the ability of canonical Wnt signaling to induce a metastable primitive endoderm state was mediated by Tbx3. Our data demonstrates a specific role for canonical Wnt signaling in promoting pluripotency while at the same time priming cells for subsequent differentiation into the primitive endoderm lineage.
authors: Sprott Center For Stem Cell Research, Ottawa Hospital Research Institute, Regenerative Medicine Program, Ottawa, Ontario, Canada.
authors: Feodor D
authors: FD
authors: Price
authors: Hang
authors: H
authors: Yin
authors: Andrew
authors: A
authors: Jones
authors: Wilfred
authors: W
authors: van Ijcken
authors: Frank
authors: F
authors: Grosveld
authors: Michael A
authors: MA
authors: Rudnicki
mesh_terms: D000818:Animals; D015153:Blotting, Western; D002460:Cell Line; D053595:Embryonic Stem Cells / Q000166:cytology* / Q000378:metabolism*; D004707:Endoderm / Q000166:cytology* / Q000378:metabolism*; D005434:Flow Cytometry; D051379:Mice; D020825:T-Box Domain Proteins / Q000235:genetics / Q000378:metabolism; D060449:Wnt Signaling Pathway / Q000235:genetics / Q000502:physiology; D060508:Wnt3 Protein / Q000235:genetics / Q000378:metabolism
chemical_list: D020825:T-Box Domain Proteins; C491460:Tbx3 protein, mouse; D060508:Wnt3 Protein