Document Detail


Formation of a primitive ectoderm like cell population, EPL cells, from ES cells in response to biologically derived factors.
MedLine Citation:
PMID:  9973595     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The primitive ectoderm of the mouse embryo arises from the inner cell mass between 4.75 and 5.25 days post coitum, around the time of implantation. Positioned at a pivotal time in development, just prior to formation of the three germ layers of the embryo proper, the primitive ectoderm responds directly to the signals generated during gastrulation. We have identified a conditioned medium, MEDII, which caused the homogeneous conversion of ES cells to a morphologically distinct cell population, termed early primitive ectoderm-like (EPL) cells. EPL cells expressed the pluripotent cell markers Oct4, SSEA1 and alkaline phosphatase. However, the formation of EPL cells was accompanied by alterations in Fgf5, Gbx2 and Rex1 expression, a loss in chimaera forming ability, changes in factor responsiveness and modified differentiation capabilities, all consistent with the identification of EPL cells as equivalent to the primitive ectoderm population of the 5.5 to 6.0 days post coitum embryo. EPL cell formation could be reversed in the presence of LIF and withdrawal of MEDII, which suggested that EPL cell formation was not a terminal differentiation event but reflected the ability of pluripotent cells to adopt distinct cell states in response to specific factors. Partial purification of MEDII revealed the presence of two separable biological activities, both of which were required for the induction and maintenance of EPL cells. We show here the first demonstration of uniform differentiation of ES cells in response to biological factors. The formation of primitive ectoderm, both in vivo and in vitro, appears to be an obligatory step in the differentiation of the inner cell mass or ES cells into cell lineages of the embryonic germ layers. EPL cells potentially represent a model for the development of lineage specific differentiation protocols and analysis of gastrulation at a molecular level. An understanding of the active components of MEDII may provide a route for the identification of factors which induce primitive ectoderm formation in vivo.
Authors:
J Rathjen; J A Lake; M D Bettess; J M Washington; G Chapman; P D Rathjen
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Journal of cell science     Volume:  112 ( Pt 5)     ISSN:  0021-9533     ISO Abbreviation:  J. Cell. Sci.     Publication Date:  1999 Mar 
Date Detail:
Created Date:  1999-05-19     Completed Date:  1999-05-19     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  0052457     Medline TA:  J Cell Sci     Country:  ENGLAND    
Other Details:
Languages:  eng     Pagination:  601-12     Citation Subset:  IM    
Affiliation:
Department of Biochemistry, University of Adelaide, North Terrace, Adelaide 5005, South Australia.
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MeSH Terms
Descriptor/Qualifier:
Animals
Antigens, CD / metabolism
Biological Factors / isolation & purification,  pharmacology
Biological Markers
COS Cells
Cell Differentiation / drug effects
Chimera
Culture Media, Conditioned
Cytokine Receptor gp130
Ectoderm / cytology*,  drug effects,  metabolism
Gastrula / cytology
Gene Expression
Humans
Membrane Glycoproteins / metabolism
Mice
Signal Transduction
Stem Cells / cytology*,  drug effects,  metabolism
Tumor Cells, Cultured
Chemical
Reg. No./Substance:
0/Antigens, CD; 0/Biological Factors; 0/Biological Markers; 0/Culture Media, Conditioned; 0/IL6ST protein, human; 0/Il6st protein, mouse; 0/Membrane Glycoproteins; 133483-10-0/Cytokine Receptor gp130

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