RGD Reference Report - NKX6.1 promotes PDX-1-induced liver to pancreatic beta-cells reprogramming. - Rat Genome Database

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NKX6.1 promotes PDX-1-induced liver to pancreatic beta-cells reprogramming.

Authors: Gefen-Halevi, S  Rachmut, IH  Molakandov, K  Berneman, D  Mor, E  Meivar-Levy, I  Ferber, S 
Citation: Gefen-Halevi S, etal., Cell Reprogram. 2010 Dec;12(6):655-64. doi: 10.1089/cell.2010.0030.
RGD ID: 8553608
Pubmed: PMID:21108535   (View Abstract at PubMed)
DOI: DOI:10.1089/cell.2010.0030   (Journal Full-text)

Reprogramming adult mammalian cells is an attractive approach for generating cell-based therapies for degenerative diseases, such as diabetes. Adult human liver cells exhibit a high level of developmental plasticity and have been suggested as a potential source of pancreatic progenitor tissue. An instructive role for dominant pancreatic transcription factors in altering the hepatic developmental fate along the pancreatic lineage and function has been demonstrated. Here we analyze whether transcription factors expressed in mature pancreatic beta-cells preferentially activate beta-cell lineage differentiation in liver. NKX6.1 is a transcription factor uniquely expressed in beta-cells of the adult pancreas, its potential role in reprogramming liver cells to pancreatic lineages has never been analyzed. Our results suggest that NKX6.1 activates immature pancreatic markers such as NGN-3 and ISL-1 but not pancreatic hormones gene expression in human liver cells. We hypothesized that its restricted capacity to activate a wide pancreatic repertoire in liver could be related to its incapacity to activate endogenous PDX-1 expression in liver cells. Indeed, the complementation of NKX6.1 by ectopic PDX-1 expression substantially and specifically promoted insulin expression and glucose regulated processed hormone secretion to a higher extent than that of PDX-1 alone, without increasing the reprogrammed cells. This may suggest a potential role for NKX6.1 in promoting PDX-1 reprogrammed cells maturation along the beta-cell-like lineage. By contrast, NKX6.1 repressed PDX-1 induced proglucagon gene expression. The individual and concerted effects of pancreatic transcription factors in adult extra-pancreatic cells, is expected to facilitate developing regenerative medicine approaches for cell replacement therapy in diabetics.

Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
glucose mediated signaling pathway involved_inIDA 8553608PMID:21108535BHF-UCL 
positive regulation of transcription by RNA polymerase II involved_inIMP 8553608PMID:21108535BHF-UCL 
type B pancreatic cell differentiation involved_inIMP 8553608PMID:21108535BHF-UCL 

Objects Annotated

Genes (Rattus norvegicus)
Pdx1  (pancreatic and duodenal homeobox 1)


Additional Information