Expression of transforming growth factor-β3 by embryonal carcinoma cells, parietal endoderm-like cells and early mouse embryos

Campbell, Wendy J.; Kelly, David L.; Rizzino, Angie

doi:10.1007/bf02623696

Cited by 15 publications

(7 citation statements)

References 14 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…As this activity is heat stable up to 95°C and correlates with TGF-p3 mRNA expression, we propose that this activity is TGF-P3. Campbell et al (1990) and Missero et al (1991) report similar findings for PYS-2 cells and dermal fibroblasts, respectively; a residual activity after neutralization of TGF-p1 and TGF-p2 correlates with expression of TGF-P3. The expression of Brachyury (T) as a marker for embryonic mesoderm demonstrates to the mesenchymal character of the cells after LIF/DIA deprivation.…”

Section: Discussionsupporting

confidence: 77%

Secretion of transforming growth factor‐β isoforms by embryonic stem cells: Isoform and latency are dependent on direction of differentiation

Slager

Freund

Buiting³

et al. 1993

Journal Cellular Physiology

View full text Add to dashboard Cite

Murine embryonic stem (ES) cells are maintained in an undifferentiated state when cultured in medium conditioned by Buffalo rat liver (BRL) cells. BRL conditioned medium (CM) contains a differentiation inhibitory activity (DIA) that is synonymous with leukemia inhibitory factor (LIF). ES cells in monolayer culture can be induced to differentiate by addition of all-trans retinoic acid (RA) to the BRL CM, when they mainly form cells resembling parietal endoderm, or by culture in medium not conditioned by BRL cells. ES cells thus deprived of LIF/DIA differentiate spontaneously to a cell type that expresses Brachyury (T), a marker of early mesoderm. Northern blot analyses have shown previously that transcripts for transforming growth factor beta 1 (TGF-beta 1) are detected in undifferentiated cells while transcripts for TGF-beta 2 and TGF-beta 3 only become detectable after differentiation. We have now determined levels of TGF-beta protein in CM and in the extracellular matrix (ECM) and have used neutralizing antibodies specific for TGF-beta 1 and TGF-beta 2 that do not react with recombinant human TGF-beta 3 to determine the isoform secreted. Using the growth inhibition of mink lung CCL64 cells as a bioassay for TGF-beta activity, we demonstrate that undifferentiated ES cells secrete latent TGF-beta 1 into the medium but no activity is found in their ECM. Cells induced to differentiate with RA contain TGF-beta 2 in both active and latent forms in their CM. Likewise their ECM contains TGF-beta 2 as the sole isoform. ES cells deprived of LIF/DIA secrete both TGF-beta 1 and TGF-beta 2 isoforms in their CM but TGF-beta-like activity remains after addition of neutralizing antibodies for TGF-beta 1 and TGF-beta 2. This active TGF beta is the major component of the TGF-beta activity in this CM. By contrast, ECM from LIF/DIA deprived cells contains only the TGF-beta 1 and beta 2 isoforms. The remaining activity in CM correlates with high expression of TGF-beta 3 by Northern blot analysis in these cells. We speculate that TGF-beta 3 is secreted by these cells and may be activated more efficiently and/or in a different manner to TGF-beta 1 and TGF-beta 2, since it is present in CM only in its active form.

show abstract

Section: Discussionsupporting

confidence: 77%

Secretion of transforming growth factor‐β isoforms by embryonic stem cells: Isoform and latency are dependent on direction of differentiation

Slager

Freund

Buiting³

et al. 1993

Journal Cellular Physiology

View full text Add to dashboard Cite

show abstract

“…With respect to the possibility that TGF-p2 itself may be a mediator of implantation, blastocysts have been shown to express various growth factors including the TGF-Ps, transforming growth factor-a, Kaposi's sarcoma type fibroblast growth factor, platelet derived growth factor A [Campbell et al, 1990;Rappolee et al, 1988, 19901, as well as growth factor receptors: insulin like growth factor receptor-I and I1 [Rappolee et al, 19901, the epidermal growth factor receptor [EGF-R; Adamson and Meek, 1984;Paria and Dey, 19901, and TGF-P receptors [Paria et al, 19921. Cooperative factors during co-culture of blastocysts in vitro stimulate the rate of blastocoel formation as well as the number of cells in the embryo [Paria and Dey, 19901.…”

Section: Implantation and Tgf-pmentioning

confidence: 99%

Transforming growth factor‐β in the early mouse embryo: Implications for the regulation of muscle formation and implantation

et al. 1993

View full text Add to dashboard Cite

In a search for functions of transforming growth factor-beta during early embryonic development we used two different experimental approaches. In the first we made use of embryonic stem (ES) cells. ES cells in culture differentiate to derivatives of all three germ layers and mimic some aspects of organogenesis when grown as aggregates in suspension to form embryoid bodies. Differentiation proceeds further when the embryoid bodies attach to suitable substrates. Muscle and neuronal cells are among the most readily identified cell types then formed. We examined the effect of all-trans retinoic acid (RA) and members of the transforming growth factor-beta family (TGF-beta 1, TGF-beta 2) under these conditions in an assay where single aggregates formed in hanging microdrops in medium supplemented with serum depleted of lipophilic substances which would include retinoids. Endoderm-like cells formed under all conditions tested. RA at concentrations of 10(-8) M and 10(-7) M induced the formation of neurons but in the absence of RA or at concentrations up to 10(-9) M, neurons were not observed. Instead, beating muscle formed in about one-third of the plated aggregates; this was greatly reduced when RA concentrations increased above 10(-9) M. Immunofluorescent staining for muscle specific myosin showed that two muscle cell types could be distinguished: elongated, non-contractile myoblasts and mononucleate flat cells. The mononucleate flat cells appeared to correspond with rhythmically contracting muscle. The number of non-contractile myoblasts increased 3-fold over controls in the presence of 10(-9) M RA. TGF-beta s increased the number of contractile and non-contractile muscle cells by a factor 3 to 7 over controls, depending on the TGF-beta isoform added and the muscle cell type formed. TGF-beta 2 also invariably increased the rate at which contracting muscle cells were first observed in replated aggregates. The stimulatory effect of TGF-beta s on the formation of mononucleate flat cells was completely abrogated by RA at 10(-9) M while the number of myoblasts under similar conditions was unchanged. These data suggest that a complex interplay between retinoids and TGF-beta isoforms may be involved in regulation of differentiation in early myogenesis. In the second approach, neutralizing polyclonal rabbit antibodies specific for TGF-beta 2 were injected into the cavity of mouse blastocysts 3.5 days post coîtum (pc). After 1 day in culture, embryos were transferred to pseudopregnant females. The number of decidua, embryos and resorptions were counted at day 8.5-9.5 pc.(ABSTRACT TRUNCATED AT 400 WORDS)

show abstract

“…Based on these activities and the defined spatial and temporal pattern of expression of the three mammalian isoforms of TGF-␤ (TGF-␤1, TGF-␤2, and TGF-␤3) during mouse embryogenesis, it has been argued that the TGF-␤s play important roles in the generation and modification of extracellular signals that direct critical processes during mammalian development (5)(6)(7)(8)(9)(10)(11)(12). This is borne out by the induction of fetal defects in embryos that are unable to produce the different isoforms of TGF-␤ (13)(14)(15)(16)(17), in particular TGF-␤2, and in embryos that cannot produce functional TGF-␤ receptors due to inactivation of the T␤R-II gene by gene targeting (18).…”

mentioning

confidence: 99%

Transcriptional Activation of the Type II Transforming Growth Factor-β Receptor Gene upon Differentiation of Embryonal Carcinoma Cells

Kelly¹,

Kim²,

Rizzino³

1998

Journal of Biological Chemistry

Self Cite

View full text Add to dashboard Cite

Expression of transforming growth factor-β3 by embryonal carcinoma cells, parietal endoderm-like cells and early mouse embryos

Cited by 15 publications

References 14 publications

Secretion of transforming growth factor‐β isoforms by embryonic stem cells: Isoform and latency are dependent on direction of differentiation

Secretion of transforming growth factor‐β isoforms by embryonic stem cells: Isoform and latency are dependent on direction of differentiation

Transforming growth factor‐β in the early mouse embryo: Implications for the regulation of muscle formation and implantation

Transcriptional Activation of the Type II Transforming Growth Factor-β Receptor Gene upon Differentiation of Embryonal Carcinoma Cells

Contact Info

Product

Resources

About