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- W2475003015 abstract "Bone morphogenetic proteins (BMPs) have been identified as key regulatory molecules in the determination of cell fate in the developing ectoderm of invertebrates, mouse and chick. In contrast, little is known about the activity of BMP signalling in the human embryonic ectoderm and the specification of neural and epithelial lineages. In this study, we have used the clonal human embryonal carcinoma (EC) stem cell line, TERA2.cl.SP12, to investigate the role of BMPs in the formation of neural and epithelial tissues. Retinoic acid (RA) treatment of TERA2.cl.SP12 cells results in the loss of stem cell markers and the attainment of both neural and epithelial-like markers in adherent culture conditions. In contrast, when RA treated TERA2.cl.SP12 cells are cultured in suspension they form aggregates and show a strong up-regulation of neural differentiation and inhibition of epithelial development. BMPs have been characterized as strong endogenous repressors of neural fate. We propose that decreased BMP signalling may be the mechanism by which neural differentiation is enhanced when TERA2.cl.SP12 cells are grown in suspension. Treatment of TERA2.cl.SP12 cells with recombinant BMP2 blocked RA-induced neural differentiation in both adherent and suspension cultures and up-regulates the expression of epithelial associated proteins (as detected by immunostaining and Western blot analysis). Conversely, neural differentiation was notably up-regulated in differentiating adherent TERA2.cl.SP12 cells by cotreatment or pretreatment with the BMP antagonist Noggin. RT-PCR analysis indicated that the expression of homeobox genes downstream of BMP signalling increased following RA induction in adherent monolayers, but not cultures grown in suspension. Such patterns of differentiation have lead us to hypothesize that TERA2.cl.SP12 closely resemble cells of the embryonic ectoderm. Indeed, initial RT-PCR studies confirm that undifferentiated TERA2.cl.SP12 cells express genes associated with the primitive ectoderm whereas markers specific to endoderm or mesoderm were not detected. Accordingly, elucidation of the role of BMP signalling in neural fate specification using TERA2.cl.SP12 cells is likely to generate important insights into neural fate decisions made in the developing human embryonic ectoderm." @default.
- W2475003015 created "2016-07-22" @default.
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- W2475003015 date "2004-12-01" @default.
- W2475003015 modified "2023-09-27" @default.
- W2475003015 title "18: Determination of neural and epithelial cell fate in the human embryonic ectoderm: the role of bone morphogenetic proteins" @default.
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