Synergistic action of Wnt and LIF in maintaining pluripotency of mouse ES cells.
Leukaemia inhibitory factor (LIF) was the first soluble factor identified as having potential to maintain the pluripotency of mouse embryonic stem (ES) cells. Recently, a second factor, Wnt, with similar activity was found. However, the relationship between these completely different signals mediating the overlapping functions is still unclear. Here, we report that the conditioned medium of L cells expressing Wnt3a maintains ES cells in the undifferentiated state in feeder-free culture, followed by expression of stem cell markers and their ability to generate germline chimaeras. However, although the activity of this conditioned medium is dependent on Wnt3a, recombinant Wnt3a protein cannot maintain ES cells in the undifferentiated state. As supplementation with Wnt3a to the sub-threshold level of LIF alone was not sufficient to maintain ES self-renewal, the results of maintenance of the undifferentiated state indicated the synergistic action of Wnt and LIF. Induction of constitutively activated beta-catenin alone is unable to maintain ES self-renewal but shows a synergistic effect with LIF. These observations indicate that the Wnt signal mediated by the canonical pathway is not sufficient but enhances the effect of LIF to maintain self-renewal of mouse ES cells.
Ogawa
Kazuya
K
Laboratory for Pluripotent Cell Studies, RIKEN Center for Developmental Biology, 2-2-3 Minatojima-Minamimachi, Chuo-ku, Kobe 650-0047, Japan.
Nishinakamura
Ryuichi
R
Iwamatsu
Yuko
Y
Shimosato
Daisuke
D
Niwa
Hitoshi
H
D000818:Animals; D002454:Cell Differentiation; D017077:Culture Media, Conditioned / Q000737:chemistry / Q000494:pharmacology; D004622:Embryo, Mammalian / Q000166:cytology; D015850:Interleukin-6 / Q000378:metabolism* / Q000494:pharmacology; D053605:Leukemia Inhibitory Factor; D051379:Mice; D039904:Pluripotent Stem Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism*; D051153:Wnt Proteins / Q000032:analysis / Q000378:metabolism* / Q000494:pharmacology; D060508:Wnt3 Protein; D060509:Wnt3A Protein; D051176:beta Catenin / Q000378:metabolism
D017077:Culture Media, Conditioned; D015850:Interleukin-6; D053605:Leukemia Inhibitory Factor; C507838:Lif protein, mouse; D051153:Wnt Proteins; D060508:Wnt3 Protein; D060509:Wnt3A Protein; C555511:Wnt3a protein, mouse; D051176:beta Catenin