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EMBRYONIC STEM CELLS

Lymphoid Enhancer Factor 1-Mediated Wnt Signaling Promotes the Initiation of Trophoblast Lineage Differentiation in Mouse Embryonic Stem Cells

Department of Animal and Avian Sciences, University of Maryland, College Park, Maryland, USA

Key Words. Caudal-related homeobox 2 • Cell differentiation • Trophoblast • Stem cells

Correspondence: Carol L. Keefer, Ph.D., Department of Animal and Avian Sciences, University of Maryland, College Park, Maryland 20742, USA. Telephone: 301-405-3933; Fax: 301-314-9059; e-mail: ckeefer{at}umd.edu

Received May 9, 2007; accepted for publication January 2, 2008.
First published online in STEM CELLS EXPRESS   January 10, 2008.



Embryonic stem (ES) cells can differentiate into all three embryonic germ layers but rarely into trophectoderm (TE) lineages that contribute to the placenta, although TE differentiation can be initiated by genetic manipulation of key genes involved in TE development. We demonstrate that Wnt signaling can initiate TE lineage differentiation by triggering an appropriate cue, caudal-related homeobox 2 (Cdx2). Overexpression and RNA interference knockdown studies indicate that Cdx2 induction in response to Wnt3a is mediated by lymphoid enhancer factor 1, whose expression is regulated by leukemia inhibitory factor (LIF) and bone morphogenetic protein. Removal of LIF, along with addition of Wnt3a, stimulated Cdx2 expression and induced formation of trophoblast stem (TS) cells. These TS cells were able to differentiate into cells with characteristics of spongiotrophoblast and trophoblast giant cells. This is, to our knowledge, the first evidence that TE lineage differentiation can be induced by Wnt signaling in mouse ES cells.

Disclosure of potential conflicts of interest is found at the end of this article.