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 Δ46–110) ES cells. Tpo plus LIF acted synergistically on the Shp-2 Δ46–110 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.
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