title: A localized Wnt signal orients asymmetric stem cell division in vitro.
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.
authors.affiliation: 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. shabib@stanford.edu
authors.forename: Shukry J
authors.initials: SJ
authors.lastname: Habib
authors.forename: Bi-Chang
authors.initials: BC
authors.lastname: Chen
authors.forename: Feng-Chiao
authors.initials: FC
authors.lastname: Tsai
authors.forename: Konstantinos
authors.initials: K
authors.lastname: Anastassiadis
authors.forename: Tobias
authors.initials: T
authors.lastname: Meyer
authors.forename: Eric
authors.initials: E
authors.lastname: Betzig
authors.forename: Roel
authors.initials: R
authors.lastname: Nusse
mesh_terms: D000818:Animals; D060049:Asymmetric Cell Division; D002454:Cell Differentiation; D002478:Cells, Cultured; D018385:Centrosome / Q000502:physiology; D048749:Cytokinesis; D053595:Embryonic Stem Cells / Q000166:cytology* / Q000378:metabolism*; D015870:Gene Expression; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008938:Mitosis; D000071317:Nanog Homeobox Protein; D050814:Octamer Transcription Factor-3 / Q000235:genetics / Q000378:metabolism; D039904:Pluripotent Stem Cells / Q000502:physiology; D011994:Recombinant Proteins / Q000378:metabolism; D059010:Single-Cell Analysis; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D051153:Wnt Proteins / Q000378:metabolism; D060449:Wnt Signaling Pathway; D000071818:Wnt-5a Protein; D060509:Wnt3A Protein / Q000378:metabolism*; D051176:beta Catenin / Q000378:metabolism
chemical_list: D018398:Homeodomain Proteins; D000071317:Nanog Homeobox Protein; C475540:Nanog protein, mouse; D050814:Octamer Transcription Factor-3; C494174:Pou5f1 protein, mouse; D011994:Recombinant Proteins; C513672:Zfp42 protein, mouse; D014157:Transcription Factors; D051153:Wnt Proteins; D000071818:Wnt-5a Protein; D060509:Wnt3A Protein; C555511:Wnt3a protein, mouse; C438615:Wnt5a protein, mouse; D051176:beta Catenin