Novel STAT3 Target Genes Exert Distinct Roles in the Inhibition of Mesoderm and Endoderm Differentiation in Cooperation with Nanog

Bourillot, Pierre‐Yves; Aksoy, Irène; Schreiber, Valérie; Wianny, Florence; Schulz, Herbert; Hummel, Oliver; Hübner, Norbert; Savatier, Pierre

doi:10.1002/stem.110

Cited by 171 publications

(196 citation statements)

References 40 publications

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“…Another line of reasoning derives from known mTOR links to some cyr61 transcription regulators. The transcription factors involved in the control of cyr61 expression in various cellular models include TCF4 (26), SRF (62), CBP (62), CREB (63), FOXO3a (64), AP1 (27,63), STAT3 (65), and HIF1␣ (27). The most obvious link is HIF1␣, known as an mTOR effector induced under hypoxic conditions (9).…”

Section: Discussionmentioning

confidence: 99%

Cyr61, a Matricellular Protein, Is Needed for Dendritic Arborization of Hippocampal Neurons

Malik¹,

Urbańska²,

Gozdz³

et al. 2013

Journal of Biological Chemistry

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Section: Discussionmentioning

confidence: 99%

Cyr61, a Matricellular Protein, Is Needed for Dendritic Arborization of Hippocampal Neurons

Malik¹,

Urbańska²,

Gozdz³

et al. 2013

Journal of Biological Chemistry

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“…Klf4 has been confirmed as a direct target of Stat3 (Bourillot et al 2009;Hall et al 2009) and when overexpressed can confer partial LIF independence to ESC propagation (Niwa et al 2009). Klf4 does not fully reproduce the effect of LIF, however, indicating that additional Stat3 targets contribute significantly.…”

Section: A Transcription Factor Network That Sustains Naïve Pluripotencymentioning

confidence: 99%

Pluripotency in the Embryo and in Culture

Nichols

Smith

2012

Cold Spring Harbor Perspectives in Biology

267

254

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SUMMARYSpecific cells within the early mammalian embryo have the capacity to generate all somatic lineages plus the germline. This property of pluripotency is confined to the epiblast, a transient tissue that persists for only a few days. In vitro, however, pluripotency can be maintained indefinitely through derivation of stem cell lines. Pluripotent stem cells established from the newly formed epiblast are known as embryonic stem cells (ESCs), whereas those generated from later stages are called postimplantation epiblast stem cells (EpiSCs). These different classes of pluripotent stem cell have distinct culture requirements and gene expression programs, likely reflecting the dynamic development of the epiblast in the embryo. In this chapter we review current understanding of how the epiblast forms and relate this to the properties of derivative stem cells. We discuss whether ESCs and EpiSCs are true counterparts of different phases of epiblast development or are culture-generated phenomena. We also consider the proposition that early epiblast cells and ESCs may represent a naïve ground state without any prespecification of lineage choice, whereas later epiblasts and EpiSCs may be primed in favor of particular fates.

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“…S3C and D), which excludes any direct or indirect involvement of JAK kinases in SYK-mediated STAT3 activation. We next used the U95Av2 GeneChip microarrays from Affymetrix to interrogate the expression levels of validated STAT3 target genes (20) before and after induction of SYK expression in the U373 expression platform (Fig. 1G, SI Text).…”

mentioning

confidence: 99%

STAT3 is a substrate of SYK tyrosine kinase in B-lineage leukemia/lymphoma cells exposed to oxidative stress

Uckun

Qazi

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

127

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We provide unprecedented genetic and biochemical evidence that the antiapoptotic transcription factor STAT3 serves as a substrate for SYK tyrosine kinase both in vitro and in vivo. Induction of SYK in an ecdysone-inducible mammalian expression system results in STAT3 activation, as documented by tyrosine phosphorylation and nuclear translocation of STAT3, as well as amplified expression of several STAT3 target genes. STAT3 activation after oxidative stress (OS) is strongly diminished in DT40 chicken B-lineage lymphoma cells rendered SYK-deficient by targeted disruption of the syk gene. Introduction of a wild-type, C-terminal or N-terminal SH2 domain-mutated, but not a kinase domain-mutated, syk gene into SYK-deficient DT40 cells restores OS-induced enhancement of STAT-3 activity. Thus, SYK plays an important and indispensable role in OS-induced STAT3 activation and its catalytic SH1 domain is critical for this previously unknown regulatory function. These results provide evidence for the existence of a novel mode of cytokineindependent cross-talk that operates between SYK and STAT3 pathways and regulates apoptosis during OS. We further provide experimental evidence that SYK is capable of associating with and phosphorylating STAT3 in human B-lineage leukemia/lymphoma cells challenged with OS. In agreement with a prerequisite role of SYK in OS-induced STAT3 activation, OS does not induce tyrosine phosphorylation of STAT3 in SYK-deficient human proB leukemia cells. Notably, inhibition of SYK with a small molecule drug candidate prevents OS-induced activation of STAT3 and overcomes the resistance of human B-lineage leukemia/lymphoma cells to OSinduced apoptosis.apoptosis | cancer | radiation

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Novel STAT3 Target Genes Exert Distinct Roles in the Inhibition of Mesoderm and Endoderm Differentiation in Cooperation with Nanog

Cited by 171 publications

References 40 publications

Cyr61, a Matricellular Protein, Is Needed for Dendritic Arborization of Hippocampal Neurons

Cyr61, a Matricellular Protein, Is Needed for Dendritic Arborization of Hippocampal Neurons

Pluripotency in the Embryo and in Culture

STAT3 is a substrate of SYK tyrosine kinase in B-lineage leukemia/lymphoma cells exposed to oxidative stress

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