Self-renewal of teratocarcinoma and embryonic stem cells

Chambers, Ian; Smith, Austin

doi:10.1038/sj.onc.1207930

Cited by 485 publications

(377 citation statements)

References 93 publications

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“…In undifferentiated mES cells, ERβ was expressed constitutively at relatively low levels. We estimated approximately 400 ERβ molecules per cell by ligand binding assay using 3 H-E 2 (data not shown). ERα was not expressed in undifferentiated mES cells or in the immediate 5 days following LIF withdrawal, but was expressed by day 7-8 in EBs (Figure 1; immunohistochemistry data not shown).…”

Section: Mechanism Of Pr Gene Induction During Differentiation Inducementioning

confidence: 99%

“…Embryonic stem (ES) cells are defined by the properties of pluripotency and self-renewal, and are capable of differentiating into cell lineages from all three germ layers as well as into germ cells [1][2][3][4][5]. They are derived from the inner cell mass of blastocysts and provide a powerful model system to study the molecular mechanisms regulating early and late lineage specific differentiation.…”

Section: Introductionmentioning

confidence: 99%

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Differentiation of murine embryonic stem cells induces progesterone receptor gene expression

Sauter

McDermid

Weinberg

et al. 2005

Experimental Cell Research

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The role of steroid hormone receptors in very early embryonic development remains unknown. Clearly, expression during organogenesis is important for tissue-specific development. However, progesterone receptor (PR) and estrogen receptors (ERα, ERβ), are expressed during early development through the blastocyst stage in mice and other species, and yet are not essential for embryonic viability. We have utilized the mouse embryonic stem (mES) cell model to investigate the regulated expression of these receptors during differentiation. Surprisingly, one of the earliest changes in gene expression in response to a differentiation signal observed is PR gene induction. It parallels the time course of expression for the patterning genes Hoxb1 and Hoxa5. Unexpectedly, PR gene expression is not regulated in an estrogen dependent manner by endogenous ERs or by transiently overexpressed ERα. Our results suggest a potentially novel mechanism of PR gene regulation within mES cells compared to adult tissues and the possibility of unique targets of PR action during early mES cell differentiation

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Section: Mechanism Of Pr Gene Induction During Differentiation Inducementioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Differentiation of murine embryonic stem cells induces progesterone receptor gene expression

Sauter

McDermid

Weinberg

et al. 2005

Experimental Cell Research

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“…bFGF provides an important medium component for culture of cow (Gjørret and MaddoxHyttel, 2005), pig (Li et al, 2004) and all three fish species (see Table 3), but not mouse ESCs (Chambers and Smith, 2004). Therefore, FGF may have variable success as a media supplement for other species.…”

Section: Media Supplementsmentioning

confidence: 99%

“…LIF, a member of the Interleukin (IL-6) family of cytokines, signals through receptor complexes including the transmembrane receptor gp130 (Chambers and Smith, 2004). Mouse LIF is dispensable for primate ESC (Carpenter et al, 2003) but vital for nonprimate mammals (excluding the dunnart) and chicken ESC cultures.…”

Section: Media Supplementsmentioning

confidence: 99%

The potential for derivation of embryonic stem cells in vertebrates

Familari

Selwood

2005

Mol. Reprod. Dev.

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An analysis of embryonic stem cell (ESC) derivation in vertebrates has revealed that the potential to form ESC is dependent on the setting aside of a pluripotent lineage from extraembryonic lineages early in development. Derivation of ESCs from all amniotes and also many lower vertebrates with that pattern of lineage allocation is thus predictable. Culture conditions during derivation in all groups share some similar characteristics, most of which are related to retaining potency coupled with extensive proliferative capacity. This in turn probably reflects the environment that maintains and causes the primordial germ cells (PGC) to proliferate in vivo. Hence culture usually involves feeder layers and serum or factors derived from them and the use of small clumps of pluriblast or epiblast cells instead of total dissociation, to facilitate cell-cell signalling. Currently addition of FGF has proven to be important but that of LIF has not been fully explored. Mol. Reprod. Dev. 73: 123-131, 2006. ß 2005 Wiley-Liss, Inc.

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“…In order to be able to exploit the rapid culture methods and safety of hESCs and hiPSCs for therapeutic purposes, it will be important to elucidate the molecular mechanisms that control the self-renewal and differentiation of ESCs. Many factors that control ESC pluripotency have now been identified and it has been demonstrated that an appropriate balance among several extrinsic signaling pathways is required for the maintenance of pluripotency [6][7][8]. However, the underlying molecular mechanisms that determine the regulation of these extrinsic signaling pathways in ESCs remain unknown.…”

Section: Introductionmentioning

confidence: 99%

LacdiNAc (GalNAcβ1-4GlcNAc) Contributes to Self-Renewal of Mouse Embryonic Stem Cells by Regulating Leukemia Inhibitory Factor/STAT3 Signaling

et al. 2011

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Self-renewal of mouse embryonic stem cells (mESCs) is maintained by leukemia inhibitory factor (LIF)/signal transducer and activator of transcription (STAT3) signaling. However, this signaling control does not function in neither mouse epiblast stem cells (mEpiSCs) nor human ESCs (hESCs) or human induced pluripotent stem cells (hiPSCs). To date, the underlying molecular mechanisms that determine this differential LIF-responsiveness have not been clarified. Here, we show that the cell surface glycan LacdiNAc (GalNAcb1-4GlcNAc) is required for LIF/ STAT3 signaling. Undifferentiated state mESCs expressed LacdiNAc at a higher level than differentiated state cells. Knockdown of b4GalNAc-T3 reduced LacdiNAc expression and caused a decrease in LIF/STAT3 signaling that lessened the rate of self-renewal of mESCs. A biochemical analysis showed that LacdiNAc expression on LIF receptor (LIFR) and gp130 was required for the stable localization of the receptors with lipid raft/caveolar components, such as caveolin-1. This localization is required for transduction of a sufficiently strong LIF/STAT3 signal. In primed state pluripotent stem cells, such as hiPSCs and mEpiSC-like cells produced from mESCs, LacdiNAc expression on LIFR and gp130 was extremely weak and the level of localization of these receptors on rafts/caveolae was also low. Furthermore, knockdown of b4GalNAc-T3 decreased LacdiNAc expression and reduced the efficiency of reversion of primed state mEpiSC-like cells into naïve state mESCs. These findings show that the different LIF-responsiveness of naïve state (mESCs) and primed state (mEpiSCs, hESCs, and hiPSCs) cells is dependent on the expression of LacdiNAc on LIFR and gp130 and that this expression is required for the induction and maintenance of the naïve state. STEM CELLS 2011;29:641-650 Disclosure of potential conflicts of interest is found at the end of this article.

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Self-renewal of teratocarcinoma and embryonic stem cells

Cited by 485 publications

References 93 publications

Differentiation of murine embryonic stem cells induces progesterone receptor gene expression

Differentiation of murine embryonic stem cells induces progesterone receptor gene expression

The potential for derivation of embryonic stem cells in vertebrates

LacdiNAc (GalNAcβ1-4GlcNAc) Contributes to Self-Renewal of Mouse Embryonic Stem Cells by Regulating Leukemia Inhibitory Factor/STAT3 Signaling

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