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EMBRYONIC STEM CELLS: CONCISE REVIEW

Lefty at the Crossroads of "Stemness" and Differentiative Events

^aDepartment of Obstetrics and Gynecology, Stony Brook University, Stony Brook, New York, USA;
^bLaboratory of Molecular Vertebrate Embryology, The Rockefeller University, New York, New York, USA

Key Words. Endometrial bleeding associated factor • Lefty • Embryonic stem cells • Review

Correspondence: Siamak Tabibzadeh, M.D., P.O. Box 160, Albertson, New York 11507-0160, USA. Telephone: 516-484-2831; Fax: 516-801-1943; e-mail: tabibzadeh{at}bioscience.org

Received February 6, 2006; accepted for publication May 16, 2006.
First published online in STEM CELLS EXPRESS   May 25, 2006.



Stem cells are functionally defined by their ability to self-renew and generate a progeny capable of creation or reconstitution of various tissues. Microarray analysis has shown a member of the transforming growth factor (TGF)-ß superfamily, Lefty, to be the single most abundant inhibitor in stem cells and in maternal decidua that supports embryo implantation. Lefty is regulated by pathways such as Smad (Sma and Mad [mothers against decapentaplegic]) and WNT (wingless-type) and by the transcriptional factor Oct3/4 (octamer-binding transcription factor 3/4), which support "stemness." Lefty is also induced upon exit from the state of stemness, including forced in vitro differentiation, and leukemia inhibitory factor withdrawal. Lefty is a candidate in cell-fate decisions because of its unique ability to modulate the expression of TGF-ß family proteins such as Nodal and by blanket inhibition of the activity of members of this family which require EGF-CFC (epidermal growth factor-Cripto, Frl-1, and Cryptic) as a coreceptor.

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