TAT-mediated neurogenin 3 protein transduction stimulates pancreatic endocrine differentiation in vitro

Juan Domínguez-Bendala, Dagmar Klein, Melina Ribeiro, Camillo Ricordi, Luca Inverardi, Ricardo Pastori, Helena Edlund

Research output: Contribution to journalArticle

70 Scopus citations

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. Nenrogenin 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.

Original languageEnglish (US)
Pages (from-to)720-726
Number of pages7
JournalDiabetes
Volume54
Issue number3
DOIs
StatePublished - Mar 1 2005

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism

Fingerprint Dive into the research topics of 'TAT-mediated neurogenin 3 protein transduction stimulates pancreatic endocrine differentiation in vitro'. Together they form a unique fingerprint.

  • Cite this