title: Thrombopoietin acts synergistically with LIF to maintain an undifferentiated state of embryonic stem cells homozygous for a Shp-2 deletion mutation.
abstract: Thrombopoietin (Tpo) and its receptor, c-mpl, are expressed in murine embryonic stem (ES) cells. ES cells are maintained in a pluripotent state by leukemia inhibitory factor (LIF) via activation of the Janus kinase (Jak)-STAT3 signaling pathway. Tpo, like LIF, activates STAT3. We report that Tpo increases the number of undifferentiated colonies derived from wild type or Shp-2 mutant (Shp-2(Delta46-110)) ES cells. Tpo plus LIF acted synergistically on the Shp-2(Delta46-110) ES cells to maintain undifferentiated colonies but no evidence of synergism via Jak-STAT3 activation was detected. Collectively, these data suggest that Tpo can play a role in preventing ES cell differentiation via Jak-STAT3 activation and perhaps via novel pathways that are enhanced in the absence of functional Shp-2.
authors.affiliation: Department of Pediatrics, Herman B Wells Center for Pediatric Research, Indiana University School of Medicine, 1044 W. Walnut Street, Indianapolis, IN 46202, USA.
authors.forename: Xiaodong
authors.initials: X
authors.lastname: Xie
authors.forename: Rebecca J
authors.initials: RJ
authors.lastname: Chan
authors.forename: Mervin C
authors.initials: MC
authors.lastname: Yoder
mesh_terms: D002454:Cell Differentiation; D002478:Cells, Cultured; D004268:DNA-Binding Proteins / Q000502:physiology; D004622:Embryo, Mammalian / Q000166:cytology; D004625:Embryo, Nonmammalian; D006131:Growth Inhibitors / Q000502:physiology*; D006720:Homozygote; D015850:Interleukin-6; D047908:Intracellular Signaling Peptides and Proteins; D053605:Leukemia Inhibitory Factor; D008222:Lymphokines / Q000502:physiology*; D009154:Mutation; D054592:Protein Tyrosine Phosphatase, Non-Receptor Type 11; D017027:Protein Tyrosine Phosphatases / Q000235:genetics*; D050796:STAT3 Transcription Factor; D017384:Sequence Deletion; D013234:Stem Cells / Q000166:cytology*; D013926:Thrombopoietin / Q000502:physiology*; D015534:Trans-Activators / Q000502:physiology
chemical_list: D004268:DNA-Binding Proteins; D006131:Growth Inhibitors; D015850:Interleukin-6; D047908:Intracellular Signaling Peptides and Proteins; D053605:Leukemia Inhibitory Factor; D008222:Lymphokines; D050796:STAT3 Transcription Factor; D015534:Trans-Activators; D013926:Thrombopoietin; D054592:Protein Tyrosine Phosphatase, Non-Receptor Type 11; D017027:Protein Tyrosine Phosphatases