STAT3 activation is sufficient to maintain an undifferentiated state of mouse embryonic stem cells

Matsuda, Takehisa; Nakamura, Takanori; Nakao, Kazuki; Arai, Takao; Katsuki, Motoya; Heike, Toshio; Yokota, Takashi

doi:10.1093/emboj/18.15.4261

Cited by 807 publications

(688 citation statements)

References 40 publications

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“…As a consequence, mouse ES cells can now be cultured in the absence of embryonal fibroblast feeder-cell layers when LIF is administered to the medium [5][6][7][8]. However, human ES cells do not respond to LIF in a similar fashion and still require feeder-cell layers for support [27].…”

Section: Discussionmentioning

confidence: 99%

“…Mouse ES cells can be maintained in an undifferentiated state when cultured on fibroblast feeder cell layers or in the presence of leukemia inhibitory factor (LIF) on gelatin-coated tissue culture dishes [5][6][7][8]. LIF belongs to the interleukin (IL)-6 family of cytokines, which also includes oncostatin M, ciliary neurotropic factor, IL-11, cardiotrophin, and IL-6 [9].…”

Section: Introductionmentioning

confidence: 99%

“…The pluripotency of mouse stem cells in culture depends on LIF-activated STAT3, since mutation of either the gp130 receptor or STAT3 itself abrogated the self-renewal of ES cells and led to the onset of differentiation [5,7,8]. Consequently, mouse stem cells can be cultured and kept pluripotent on gelatin-coated tissue culture flasks when maintained in medium containing LIF.…”

Section: Introductionmentioning

confidence: 99%

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

Schuringa

Schaaf

Vellenga³

et al. 2002

Experimental Cell Research

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

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

Schuringa

Schaaf

Vellenga³

et al. 2002

Experimental Cell Research

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“…In the proposed mechanism, IL-6 binds to IL-6R and gp130 (Bravo et al 1998;Hibi et al 1990;Muller-Newen et al 2000) to form hexameric complex composed of two molecules of each component (Paonessa et al 1995;Skiniotis et al 2005;Ward et al 1996). This in turn triggers homodimerization and activation of gp130, leading to activation of the Janus kinase family (JAK1, JAK2, TYK2) of signal transducers, which further activate transcription activators (STAT1, STAT3) and mitogen-activated protein kinases (MAP-KKK, MAPKK, MAPK) (Matsuda et al 1999).…”

Section: Introductionmentioning

confidence: 99%

Growth control of hybridoma cells with an artificially induced EpoR-gp130 heterodimer

et al. 2006

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IL-6 has been known to modulate the growth of many hybridoma cells and also promote resultant antibody productivity. However, IL-6 is so expensive that the use of IL-6-dependent hybridomas for industrial antibody production is not practical. In this study, we aimed at designing antibody/gp130 and antibody/EpoR chimeras which could tightly control cell growth in response to more affordable cognate antigen. Retroviral vectors encoding V H or V L region of anti-hen egg lysozyme (HEL) antibody HyHEL-10 tethered to a pair of extracellular D2/transmembrane domains of erythropoietin receptor (EpoR) and cytoplasmic domains of either EpoR or gp130, were constructed, and a homodimeric or a heterodimeric pair of chimeric receptor combinations (V H -gp130 and V L -gp130 or V H -gp130 and V L -EpoR) were expressed in an IL-6-dependent hybridoma 7TD1. The chimeric receptor-derived growth signal was observed in both combinations, while some residual growth signal was observed in the absence of HEL. To reduce interchain interaction between the two receptor chains, we introduced mutations to the transmembrane domain of both chimera combinations. Consequently, the heterodimeric combination of V H -gp130 and V L -EpoR showed clear HEL-dependent cell growth, while the homodimeric combination of V H -gp130 and V L -gp130 showed reduced cell growth in the absence of HEL. This is the first report that an EpoR-gp130 cytoplasmic domain heterodimer could transduce a growth signal in hybridoma cells, indicating tight and economical growth control of hybridoma cells via our chimeric receptors.

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“…The cross‐talk between signaling and transcriptional levels has been widely studied in vitro in PSCs cultured in different conditions. LIF cause the activation of the LIF/JAK/Stat3 signaling pathway, through the activation of some Janus tyrosine kinases (JAK), triggering the phosphorylation of Stat3 and the activation of the expression of several genes required for mESCs and hESCs self‐renewal 46, 47, 48, 49. The combination of inhibitors in 2i and 3i culture mediums, which act on some specific genes from the Wnt/β‐catenin signaling pathway, promote pluripotency in mESCs through the stabilization of β‐catenin that override the inhibitory effect of Tcf3 on some important pluripotency regulators, such as Oct4 and Nanog 50, 51.…”

Section: Pluripotent State Gene Expression Heterogeneity Is Tightly Rmentioning

confidence: 99%

Modeling heterogeneity in the pluripotent state: A promising strategy for improving the efficiency and fidelity of stem cell differentiation

Angarica

Sol

2016

BioEssays

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Pluripotency can be considered a functional characteristic of pluripotent stem cells (PSCs) populations and their niches, rather than a property of individual cells. In this view, individual cells within the population independently adopt a variety of different expression states, maintained by different signaling, transcriptional, and epigenetics regulatory networks. In this review, we propose that generation of integrative network models from single cell data will be essential for getting a better understanding of the regulation of self‐renewal and differentiation. In particular, we suggest that the identification of network stability determinants in these integrative models will provide important insights into the mechanisms mediating the transduction of signals from the niche, and how these signals can trigger differentiation. In this regard, the differential use of these stability determinants in subpopulation‐specific regulatory networks would mediate differentiation into different cell fates. We suggest that this approach could offer a promising avenue for the development of novel strategies for increasing the efficiency and fidelity of differentiation, which could have a strong impact on regenerative medicine.

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STAT3 activation is sufficient to maintain an undifferentiated state of mouse embryonic stem cells

Abstract: Embryonic stem (ES) cells can be maintained in an

Cited by 807 publications

References 40 publications

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

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

Growth control of hybridoma cells with an artificially induced EpoR-gp130 heterodimer

Modeling heterogeneity in the pluripotent state: A promising strategy for improving the efficiency and fidelity of stem cell differentiation

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