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Science 339 (6126): 1445-1448

Copyright © 2013 by the American Association for the Advancement of Science

A Localized Wnt Signal Orients Asymmetric Stem Cell Division in Vitro

Shukry J. Habib,1,2,* Bi-Chang Chen,2 Feng-Chiao Tsai,3 Konstantinos Anastassiadis,4 Tobias Meyer,3 Eric Betzig,2 Roel Nusse1,*

Abstract: Developmental signals such as Wnts are often presented to cells in an oriented manner. To examine the consequences of local Wnt signaling, we immobilized Wnt proteins on beads and introduced them to embryonic stem cells in culture. At the single-cell level, the Wnt-bead induced asymmetric distribution of Wnt–β-catenin signaling components, oriented the plane of mitotic division, and directed asymmetric inheritance of centrosomes. Before cytokinesis was completed, the Wnt-proximal daughter cell expressed high levels of nuclear β-catenin and pluripotency genes, whereas the distal daughter cell acquired hallmarks of differentiation. We suggest that a spatially restricted Wnt signal induces an oriented cell division that generates distinct cell fates at predictable positions relative to the Wnt source.

1 Department of Developmental Biology, Howard Hughes Medical Institute, Institute for Stem Cell Biology and Regenerative Medicine, Stanford University, 265 Campus Drive, Stanford, CA 94305, USA.
2 Janelia Farm Research Campus, 19700 Helix Drive, Ashburn, VA 20147, USA.
3 Department of Chemical and Systems Biology, Stanford University, Stanford, CA 94305, USA.
4 BIOTEC, Technische Universität Dresden Tatzberg 47-51, 01307 Dresden, Germany.

* Corresponding author. E-mail: rnusse{at} (R.N.); shabib{at} (S.J.H.)

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