Linked Life Data

18192227

Source:http://linkedlifedata.com/resource/pubmed/id/18192227

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
2008-3-14
pubmed:abstractText
Human embryonic stem cells (HESCs) are unique in their capacity to self-renew while remaining pluripotent. This undifferentiated state must be actively maintained by secreted factors. To identify autocrine factors that may support HESC growth, we have taken a global genetic approach. Microarray analysis identified fibroblast growth factor 4 (FGF4) as a prime candidate for autocrine signaling. Furthermore, the addition of recombinant FGF4 to HESCs supports their proliferation. We show that FGF4 is produced by multiple undifferentiated HESC lines, along with a novel fibroblast growth factor 4 splice isoform (FGF4si) that codes for the amino-terminal half of FGF4. Strikingly, although FGF4 supports the undifferentiated growth of HESCs, FGF4si effectively counters its effect. Furthermore, we show that FGF4si is an antagonist of FGF4, shutting down FGF4-induced Erk1/2 phosphorylation. Expression analysis shows that both isoforms are expressed in HESCs and early differentiated cells. However, whereas FGF4 ceases to be expressed in mature differentiated cells, FGF4si continues to be expressed after cell differentiation. Targeted knockdown of FGF4 using small interfering RNA increased differentiation of HESCs, demonstrating the importance of endogenous FGF4 signaling in maintaining their pluripotency. Taken together, these results suggest a growth-promoting role for FGF4 in HESCs and a putative feedback inhibition mechanism by a novel FGF4 splice isoform that may serve to promote differentiation at later stages of development.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Mar
pubmed:issn
1549-4918
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
26
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
767-74
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed-meshheading:18192227-Alternative Splicing, pubmed-meshheading:18192227-Animals, pubmed-meshheading:18192227-Autocrine Communication, pubmed-meshheading:18192227-Cell Count, pubmed-meshheading:18192227-Cell Differentiation, pubmed-meshheading:18192227-Cell Proliferation, pubmed-meshheading:18192227-Cells, Cultured, pubmed-meshheading:18192227-Embryonic Stem Cells, pubmed-meshheading:18192227-Enzyme Activation, pubmed-meshheading:18192227-Fibroblast Growth Factor 4, pubmed-meshheading:18192227-Humans, pubmed-meshheading:18192227-Mice, pubmed-meshheading:18192227-Mitogen-Activated Protein Kinase 1, pubmed-meshheading:18192227-Mitogen-Activated Protein Kinase 3, pubmed-meshheading:18192227-Phosphorylation, pubmed-meshheading:18192227-Pluripotent Stem Cells, pubmed-meshheading:18192227-Protein Isoforms
pubmed:year
2008
pubmed:articleTitle
Fibroblast growth factor 4 and its novel splice isoform have opposing effects on the maintenance of human embryonic stem cell self-renewal.
pubmed:affiliation
Department of Genetics, The Life Sciences Institute, The Hebrew University, Jerusalem 91904, Israel.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't