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Blood, 15 January 2005, Vol. 105, No. 2, pp. 635-637.
Prepublished online as a Blood First Edition Paper on September 9, 2004; DOI 10.1182/blood-2004-07-2681.
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HEMATOPOIESIS
Brief report
Murine embryonic stem cell differentiation is promoted by SOCS-3 and inhibited by the zinc finger transcription factor Klf4
Yanjun Li,
Jeanette McClintick,
Li Zhong,
Howard J. Edenberg,
Mervin C. Yoder, and
Rebecca J. Chan
From the Departments of Pediatrics, Medical and Molecular Genetics, Biochemistry and Molecular Biology, and Microbiology and Immunology, Herman B Wells Center for Pediatric Research, and Center for Medical Genomics, Indiana University School of Medicine, Indianapolis, IN.
Embryonic stem (ES) cells homozygous for a Shp-2 mutation (Shp-2 46-110) demonstrate leukemia inhibitory factor (LIF) hypersensitivity and increased LIF-stimulated phosphorylation of signal transducer and activator of transcription (STAT3). We hypothesized that LIF-responsive genes in Shp-246-110 cells would represent potential candidates for molecules vital for ES cell self-renewal. Using microarray analysis, we detected 41 genes whose expression was modified by LIF in Shp-246-110 ES cells. Induction of 2 significantly up-regulated genes, suppressor of cytokine signaling–3 (SOCS-3) and Krüppel-like factor 4 (Klf4), was verified using Northern blotting. ES cells overexpressing SOCS-3 had an increased capacity to differentiate to hematopoietic progenitors, rather than to self-renew. In contrast, ES cells overexpressing Klf4 had a greater capacity to self-renew based on secondary embryoid body (EB) formation. Klf4-transduced d6 EBs expressed higher levels of Oct-4, consistent with the notion that Klf4 promotes ES cell self-renewal. These findings verify the negative role of SOCS-3 on LIF signaling and provide a novel role for Klf4 in ES cell function.
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