LIF-Induced STAT3 Signaling in Murine versus Human Embryonal Carcinoma (EC) Cells

Schuringa, Jan Jacob; Schaaf, Saskia van der; Vellenga, Edo; Eggen, Bart J. L.; Kruijer, W.

doi:10.1006/excr.2001.5454

Cited by 43 publications

(26 citation statements)

References 34 publications

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“…Abbreviations: hESC, human embryonic stem cell; RT-PCR, reverse transcription-polymerase chain reaction; SR, serum replacement. signal transduction in embryonal carcinoma cells and that the silencing of endogenous SOCS-1 in hESCs could make the culturing of these cells more feasible [23]. In our study, in Smad7 and especially Smad1, involved in a complex formation with STAT3 [24], the expression was slightly increased in HS237 cells cultured in serum medium compared with the cells cultured in SR medium.…”

Section: Discussionmentioning

confidence: 47%

Unique Gene Expression Signature by Human Embryonic Stem Cells Cultured Under Serum-Free Conditions Correlates with Their Enhanced and Prolonged Growth in an Undifferentiated Stage

et al. 2005

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Understanding the interaction between human embryonic stem cells (hESCs) and their microenvironment is crucial for the propagation and the differentiation of hESCs for therapeutic applications. hESCs maintain their characteristics both in serum-containing and serum-replacement (SR) media. In this study, the effects of the serum-containing and SR culture media on the gene expression profiles of hESCs were examined. Although the expression of many known embryonic stem cell markers was similar in cells cultured in either media, surprisingly, 1,417 genes were found to be differentially expressed when hESCs cultured in serum-containing medium were compared with those cultured in SR medium. Several genes upregulated in cells cultured in SR medium suggested increased metabolism and proliferation rates in this medium, providing a possible explanation for the increased growth rate of nondifferentiated cells observed in SR culture conditions compared with that in serum medium. Several genes characteristic for cells with differentiated phenotype were expressed in cells cultured in serum-containing medium. Our data clearly indicate that the manipulation of hESC culture conditions causes phenotypic changes of the cells that were reflected also at the level of gene expression. Such changes may have fundamental importance for hESCs, and gene expression changes should be monitored as a part of cell culture optimization aiming at a clinical use of hESCs for cell transplantation. STEM CELLS 2006;24:151-167

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Section: Discussionmentioning

confidence: 47%

Unique Gene Expression Signature by Human Embryonic Stem Cells Cultured Under Serum-Free Conditions Correlates with Their Enhanced and Prolonged Growth in an Undifferentiated Stage

et al. 2005

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“…Thus, complete restriction of MV by IFN-␤ appears to be generally applicable to rodent cells but not to primary human cells. We hypothesize that the divergence of these results between host species is due either to activation of unique antiviral signaling pathways in rodent versus human cells after addition of the two cytokines (34,41) or murine versus human species-specific differences for some of the virus-encoded anti-cytokine immunomodulators (43).…”

Section: Discussionmentioning

confidence: 99%

The Addition of Tumor Necrosis Factor plus Beta Interferon Induces a Novel Synergistic Antiviral State against Poxviruses in Primary Human Fibroblasts

Bartee

Mohamed

López

et al. 2009

J Virol

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Tumor necrosis factor (TNF) and members of the interferon (IFN) family have been shown to independently inhibit the replication of a variety of viruses. In addition, previous reports have shown that treatment with various combinations of these antiviral cytokines induces a synergistic antiviral state that can be significantly more potent than addition of any of these cytokines alone. The mechanism of this cytokine synergy and its effects on global gene expression, however, are not well characterized. Here, we use DNA microarray analysis to demonstrate that treatment of uninfected primary human fibroblasts with TNF plus IFN-␤ induces a distinct synergistic state characterized by significant perturbations of several hundred genes which are coinduced by the individual cytokines alone, as well as the induction of more than 850 novel host cell genes. This synergy is mediated directly by the two ligands, not by intermediate secreted factors, and is necessary and sufficient to completely block the productive replication and spread of myxoma virus in human fibroblasts. In contrast, the replication of two other poxviruses, vaccinia virus and tanapox virus, are only partially inhibited in these cells by the synergistic antiviral state, whereas the spread of both of these viruses to neighboring cells was efficiently blocked. Taken together, our data indicate that the combination of TNF and IFN-␤ induces a novel synergistic antiviral state that is highly distinct from that induced by either cytokine alone.Poxviruses are large enveloped DNA viruses whose replication cycle occurs exclusively in the cytoplasm (27). Although many poxviruses are highly species specific, some members, such as monkeypox virus, tanapox virus (TPV), and cowpox virus, are able to readily leap species barriers and initiate productive zoonotic infections in humans (19,23,28,30). Myxoma virus (MV), an example of more restricted host species range, is a member of the Leporipoxvirus genus, which is uniquely restricted to rabbits (10,16,47). This host species restriction is so profound that even injection of live MV into any other vertebrate species, including humans, fails to produce a productive infection. The molecular mechanisms behind this host restriction remain largely unknown; however, there is evidence that some of the host barriers to MV permissiveness outside the rabbit are regulated by antiviral cytokines such as interferon (IFN) and tumor necrosis factor (TNF) (50, 51). The issue of restriction of MV replication in primary human cells is of particular interest because MV replicates productively in a wide variety of human cancer cells and is currently being developed as a novel oncolytic virotherapeutic to treat human cancer (46). Consequently, a better understanding of the mechanisms by which MV is restricted in primary human cells and tissues is critical before MV enters human trials.Previously, our lab has shown that primary mouse fibroblasts are nonpermissive for MV replication because they induce and secrete type I IFN in response to MV in...

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“…For example, TF Foxd3 is required for mES cell self-renewal, but its expression appears to be nonessential for hES (Ginis et al 2004). Similarly, STAT3, a TF downstream to LIF signaling, is also required for self-renewal and the maintenance of pluripotency of mES cells, but it seems to be dispensable in hES cells (Schuringa et al 2002). Compared to mES cells, mEpiSCs are functionally more similar to hES cells in several ways, including their responses to BMB4 and Activin/Nodal signaling (Brons et al 2007).…”

Section: Es Cells Better Represent Icm Than Episcsmentioning

confidence: 99%

Rewirable gene regulatory networks in the preimplantation embryonic development of three mammalian species

Xie

Chen²,

Ptaszek³

et al. 2010

Genome Res.

211

224

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Mammalian preimplantation embryonic development (PED) is thought to be governed by highly conserved processes. While it had been suggested that some plasticity of conserved signaling networks exists among different mammalian species, it was not known to what extent modulation of the genomes and the regulatory proteins could “rewire” the gene regulatory networks (GRN) that control PED. We therefore generated global transcriptional profiles from three mammalian species (human, mouse, and bovine) at representative stages of PED, including: zygote, two-cell, four-cell, eight-cell, 16-cell, morula and blastocyst. Coexpression network analysis suggested that 40.2% orthologous gene triplets exhibited different expression patterns among these species. Combining the expression data with genomic sequences and the ChIP-seq data of 16 transcription regulators, we observed two classes of genomic changes that contributed to interspecies expression difference, including single nucleotide mutations leading to turnover of transcription factor binding sites, and insertion of cis-regulatory modules (CRMs) by transposons. About 10% of transposons are estimated to carry CRMs, which may drive species-specific gene expression. The two classes of genomic changes act in concert to drive mouse-specific expression of MTF2, which links POU5F1/NANOG to NOTCH signaling. We reconstructed the transition of the GRN structures as a function of time during PED. A comparison of the GRN transition processes among the three species suggested that in the bovine system, POU5F1's interacting partner SOX2 may be replaced by HMGB1 (a TF sharing the same DNA binding domain with SOX2), resulting in rewiring of GRN by a trans change.

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LIF-Induced STAT3 Signaling in Murine versus Human Embryonal Carcinoma (EC) Cells

Cited by 43 publications

References 34 publications

Unique Gene Expression Signature by Human Embryonic Stem Cells Cultured Under Serum-Free Conditions Correlates with Their Enhanced and Prolonged Growth in an Undifferentiated Stage

Unique Gene Expression Signature by Human Embryonic Stem Cells Cultured Under Serum-Free Conditions Correlates with Their Enhanced and Prolonged Growth in an Undifferentiated Stage

The Addition of Tumor Necrosis Factor plus Beta Interferon Induces a Novel Synergistic Antiviral State against Poxviruses in Primary Human Fibroblasts

Rewirable gene regulatory networks in the preimplantation embryonic development of three mammalian species

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