Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
2007-9-20
pubmed:abstractText
It is believed that adult tissues in mammals lack the plasticity needed to assume new developmental fates because of the absence of efficient pathways of dedifferentiation. However, the well-documented ability of the transcription factor pancreatic and duodenal homeobox gene 1 (PDX-1) to activate pancreatic lineage development and insulin production following ectopic expression in liver suggests a surprising degree of residual plasticity in adult liver cells. This study seeks a mechanistic explanation for the capacity of PDX-1 to endow liver cells with pancreatic characteristics and function. We demonstrate that PDX-1, previously shown to play an essential role in normal pancreatic organogenesis and pancreatic beta-cell function and to possess the potential to activate multiple pancreatic markers in liver, can also direct hepatic dedifferentiation. PDX-1 represses the adult hepatic repertoire of gene expression and activates the expression of the immature hepatic marker alpha-fetoprotein. We present evidence indicating that PDX-1 triggers hepatic dedifferentiation by repressing the key hepatic transcription factor CCAAT/enhancer-binding protein beta. Hepatic dedifferentiation is necessary though not sufficient for the activation of the mature pancreatic repertoire in liver. CONCLUSION: Our study suggests a dual role for PDX-1 in liver: inducing hepatic dedifferentiation and activating the pancreatic lineage. The identification of dedifferentiation signals may promote the capacity to endow mature tissues in mammals with the plasticity needed for acquiring novel developmental fates and functions to be implemented in the field of regenerative medicine.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Sep
pubmed:issn
0270-9139
pubmed:author
pubmed:issnType
Print
pubmed:volume
46
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
898-905
pubmed:dateRevised
2011-6-1
pubmed:meshHeading
pubmed:year
2007
pubmed:articleTitle
Pancreatic and duodenal homeobox gene 1 induces hepatic dedifferentiation by suppressing the expression of CCAAT/enhancer-binding protein beta.
pubmed:affiliation
The Endocrine Institute, Sheba Medical Center, Tel-Hashomer, Israel.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't