Role of suppressors of cytokine signaling (Socs) in leukemia inhibitory factor (LIF) -dependent embryonic stem cell survival

Mouse embryonic stem (ES) cells remain pluripotent in vitro when grown in t he presence of leukemia inhibitory factor (LIF), LIF withdrawal results in progressive ES cell differentiation. Here we show that during this differen tiation process, part of the cells undergo apoptosis concomitant with an ac tivation of the p38 MAP kinase. To gain insight into events mediated by LIF in ES cells, the expression of potential candidate genes was analyzed in t he absence or presence of this cytokine by using a semiquantitative RT-PCR assay, We focused on early response genes and on a new type of cytokine rep ressors (the Socs proteins), some of which exhibit anti-apoptotic propertie s, We found that expression of c-Fos, c-Jun, and JunB was induced upon LIF treatment whereas that of JunD, the tyrosine phosphatase ESP, and the compo nents of the LIF receptor remained unaffected, Expression of Socs-3, but no t Socs-1 or Socs-2, was stimulated in the presence of LIF. Finally, uncontr olled overexpression of Socs-1 and Socs-3 led to repression of LIF-dependen t transcription and severely reduced cell viability, suggesting that the di sturbance of a well balanced Socs protein content has adverse effects on ce ll survival.