A Localized Wnt Signal Orients Asymmetric Stem Cell Division in Vitro

• Published in: Science (American Association for the Advancement of Science) Vol. 339; no. 6126; pp. 1445 - 1448
• Main Authors: Habib, Shukry J., Chen, Bi-Chang, Tsai, Feng-Chiao, Anastassiadis, Konstantinos, Meyer, Tobias, Betzig, Eric, Nusse, Roel
• Format: Journal Article
• Language: English
• Published: United States American Association for the Advancement of Science 22.03.2013; The American Association for the Advancement of Science
• Subjects: Adenosine triphosphatase; Animals; Asymmetric Cell Division; Asymmetry; beta Catenin - metabolism; Cancer; Cell Differentiation; Cell division; Cell growth; Cells; Cells, Cultured; Cellular biology; Centrosome - physiology; Centrosomes; Cytokinesis; Daughter cells; Daughters; Division; Embryonic stem cells; Embryonic Stem Cells - cytology; Embryonic Stem Cells - metabolism; Fate; Gene Expression; Genes; Homeodomain Proteins - genetics; Homeodomain Proteins - metabolism; Individualized Instruction; Kinases; Mice; Mitosis; Nanog Homeobox Protein; Octamer Transcription Factor-3 - genetics; Octamer Transcription Factor-3 - metabolism; Pathways; Pluripotent stem cells; Pluripotent Stem Cells - physiology; Proteins; Recombinant Proteins - metabolism; Ribonucleic acids; Signals; Single-Cell Analysis; Stem cells; Transcription Factors - genetics; Transcription Factors - metabolism; Wnt Proteins - metabolism; Wnt Signaling Pathway; Wnt-5a Protein; Wnt3A Protein - metabolism
• ISSN: 0036-8075; 1095-9203
• DOI: 10.1126/science.1231077

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.