TRANSCRIPTION FACTOR STAT5 IS AN EARLY MARKER OF DIFFERENTIATION OF MURINE EMBRYONIC STEM-CELLS

Embryonic stem (ES) cells are pluripotent descendants of the inner cel l mass of blastocysts capable of differentiating into progenitor cells of most if not all tissues. The pluripotency of ES cells is maintaine d by leukemia inhibitory factor (LIF), a member of the family of inter leukin-6-type cytokines. These cytokines activate Janus tyrosine kinas es and signal transducer and activator of transcription factors (Stat) via the signalling receptor component gp130. Pluripotent ES1 cells pr oliferating in the presence of LIF were known from previous studies to contain Stat3 and Stat1 capable of transcriptional activation. Here w e report that the level of tyrosine-phosphorylated Stat3 decreases rap idly during differentiation induced by treatment of ES1 cells either w ith retinoic acid (RA) or by withdrawal of LIF. In line with this find ing, the DNA-binding activity of Stat3 decreased during differentiatio n. In contrast, Stat5 was absent from pluripotent proliferating ES cel ls, but appeared early after induction of differentiation. The positiv e correlation between induction of differentiation and expression of S tat5 mRNA was confirmed for three independent ES cell lines. Stat5 tra nscripts were detectable in ES1 cells as early as 12 h after treatment with RA and 36 h after withdrawal of LIF. Stat5 protein was detectabl e 2 days after the onset of differentiation. These results establish S tat5 as a novel marker of very early stages of differentiation of ES c ells.