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TAT-mediated neurogenin 3 protein transduction stimulates pancreatic endocrine differentiation in vitro
- Source :
- Diabetes. 54(3)
- Publication Year :
- 2005
-
Abstract
- Stem cell technologies hold great potential for the treatment of type 1 diabetes, provided that functional transplantable β-cells can be selectively generated in an efficient manner. Such a process should recapitulate, at least to a certain extent, the embryonic development of β-cells in vitro. However, progress at identifying the transcription factors involved in β-cell development has not been accompanied by a parallel success at unraveling the pattern of their instructive extracellular signals. Here we present proof of principle of a novel approach to circumvent this problem, based on the use of the HIV/TAT protein transduction domain. Neurogenin 3 (ngn3), a factor whose expression is essential for pancreatic endocrine differentiation, was fused to the TAT domain. Administration of TAT/ngn3 to cultured pancreatic explants results in efficient uptake, nuclear translocation, and stimulation of downstream reporter and endogenous genes. Consistent with the predicted activity of the protein, e9.5 and e13.5 mouse pancreatic explants cultured in the presence of TAT/ngn3 show an increased level of endocrine differentiation compared with control samples. Our results raise the possibility of sequentially specifying stem/progenitor cells toward the β-cell lineage, by using the appropriate sequence and combination of TAT-fused transcription factors.
- Subjects :
- Endocrinology, Diabetes and Metabolism
Cellular differentiation
Recombinant Fusion Proteins
Genetic Vectors
Gene Expression
Mice, Transgenic
Nerve Tissue Proteins
Biology
Cell Line
Transduction (genetics)
Islets of Langerhans
Mice
Transduction, Genetic
Gene expression
Internal Medicine
medicine
Basic Helix-Loop-Helix Transcription Factors
Animals
Progenitor cell
Transcription factor
Pancreas
Cell Differentiation
Molecular biology
Cell biology
medicine.anatomical_structure
Cell culture
Gene Products, tat
Stem cell
Subjects
Details
- ISSN :
- 00121797
- Volume :
- 54
- Issue :
- 3
- Database :
- OpenAIRE
- Journal :
- Diabetes
- Accession number :
- edsair.doi.dedup.....c7b9b74c23202b56b5544718d70b255d