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 Edenberg, Mervin Yoder, Rebecca Chan

Research output: Contribution to journalArticle

196 Citations (Scopus)

Abstract

Embryonic stem (ES) cells homozygous for a Shp-2 mutation (Shp-2 Δ46-110) 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-2Δ46-110 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-2Δ46-110 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.

Original languageEnglish
Pages (from-to)635-637
Number of pages3
JournalBlood
Volume105
Issue number2
DOIs
StatePublished - Jan 15 2005

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Zinc Fingers
Embryonic Stem Cells
Stem cells
Leukemia Inhibitory Factor
Zinc
Cell Differentiation
Transcription Factors
Cytokines
Genes
Suppressor Genes
Embryoid Bodies
Phosphorylation
Transcription
Microarray Analysis
Microarrays
Transducers
Gene expression
Northern Blotting
Hypersensitivity
Gene Expression

ASJC Scopus subject areas

  • Hematology

Cite this

Murine embryonic stem cell differentiation is promoted by SOCS-3 and inhibited by the zinc finger transcription factor Klf4. / Li, Yanjun; McClintick, Jeanette; Zhong, Li; Edenberg, Howard; Yoder, Mervin; Chan, Rebecca.

In: Blood, Vol. 105, No. 2, 15.01.2005, p. 635-637.

Research output: Contribution to journalArticle

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AU - Chan, Rebecca

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