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.
Publication types
-
Research Support, U.S. Gov't, P.H.S.
MeSH terms
-
Cell Differentiation
-
Cells, Cultured
-
DNA-Binding Proteins / physiology
-
Embryo, Mammalian / cytology
-
Embryo, Nonmammalian
-
Growth Inhibitors / physiology*
-
Homozygote*
-
Interleukin-6*
-
Intracellular Signaling Peptides and Proteins
-
Leukemia Inhibitory Factor
-
Lymphokines / physiology*
-
Mutation*
-
Protein Tyrosine Phosphatase, Non-Receptor Type 11
-
Protein Tyrosine Phosphatases / genetics*
-
STAT3 Transcription Factor
-
Sequence Deletion*
-
Stem Cells / cytology*
-
Thrombopoietin / physiology*
-
Trans-Activators / physiology
Substances
-
DNA-Binding Proteins
-
Growth Inhibitors
-
Interleukin-6
-
Intracellular Signaling Peptides and Proteins
-
Leukemia Inhibitory Factor
-
Lymphokines
-
STAT3 Transcription Factor
-
Trans-Activators
-
Thrombopoietin
-
Protein Tyrosine Phosphatase, Non-Receptor Type 11
-
Protein Tyrosine Phosphatases