| Regulation of extra-embryonic endoderm stem cell differentiation by Nodal and Cripto signaling. | |
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MedLine Citation:
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PMID: 21862554 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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The signaling pathway for Nodal, a ligand of the TGFβ superfamily, plays a central role in regulating the differentiation and/or maintenance of stem cell types that can be derived from the peri-implantation mouse embryo. Extra-embryonic endoderm stem (XEN) cells resemble the primitive endoderm of the blastocyst, which normally gives rise to the parietal and the visceral endoderm in vivo, but XEN cells do not contribute efficiently to the visceral endoderm in chimeric embryos. We have found that XEN cells treated with Nodal or Cripto (Tdgf1), an EGF-CFC co-receptor for Nodal, display upregulation of markers for visceral endoderm as well as anterior visceral endoderm (AVE), and can contribute to visceral endoderm and AVE in chimeric embryos. In culture, XEN cells do not express Cripto, but do express the related EGF-CFC co-receptor Cryptic (Cfc1), and require Cryptic for Nodal signaling. Notably, the response to Nodal is inhibited by the Alk4/Alk5/Alk7 inhibitor SB431542, but the response to Cripto is unaffected, suggesting that the activity of Cripto is at least partially independent of type I receptor kinase activity. Gene set enrichment analysis of genome-wide expression signatures generated from XEN cells under these treatment conditions confirmed the differing responses of Nodal- and Cripto-treated XEN cells to SB431542. Our findings define distinct pathways for Nodal and Cripto in the differentiation of visceral endoderm and AVE from XEN cells and provide new insights into the specification of these cell types in vivo. |
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Authors:
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Marianna Kruithof-de Julio; Mariano J Alvarez; Antonella Galli; Jianhua Chu; Sandy M Price; Andrea Califano; Michael M Shen |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural |
Journal Detail:
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Title: Development (Cambridge, England) Volume: 138 ISSN: 1477-9129 ISO Abbreviation: Development Publication Date: 2011 Sep |
Date Detail:
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Created Date: 2011-08-24 Completed Date: 2011-11-02 Revised Date: 2012-09-28 |
Medline Journal Info:
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Nlm Unique ID: 8701744 Medline TA: Development Country: England |
Other Details:
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Languages: eng Pagination: 3885-95 Citation Subset: IM |
Affiliation:
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Department of Medicine, Columbia University Medical Center, New York, NY 10032, USA. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Animals Cell Differentiation / drug effects, genetics* Cell Line Embryo, Mammalian Embryonic Stem Cells / drug effects, metabolism, physiology* Endoderm / cytology*, drug effects, metabolism, physiology* Epidermal Growth Factor / genetics, metabolism, pharmacology, physiology* Extraembryonic Membranes / cytology, physiology Female Gene Expression Profiling Membrane Glycoproteins / genetics, metabolism, pharmacology, physiology* Mice Mice, Inbred ICR Mice, Transgenic Microarray Analysis Neoplasm Proteins / genetics, metabolism, pharmacology, physiology* Nodal Protein / genetics, metabolism, pharmacology, physiology* Pregnancy Signal Transduction / drug effects, genetics |
| Grant Support | |
ID/Acronym/Agency:
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HD42837/HD/NICHD NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Membrane Glycoproteins; 0/Neoplasm Proteins; 0/Nodal Protein; 0/Nodal protein, mouse; 0/Tdgf1 protein, mouse; 62229-50-9/Epidermal Growth Factor |
| Comments/Corrections | |
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