Cellular origins of adult human islet in vitro dedifferentiation

  1. Get@NRC: Cellular origins of adult human islet in vitro dedifferentiation (Opens in a new window)
DOIResolve DOI: http://doi.org/10.1038/labinvest.2008.41
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Journal titleLaboratory Investigation
Pages761772; # of pages: 12
SubjectAdult; bio; cells; fluorescence; human; in vitro; insulin; protein; somatostatin; surgery; vitro; β-cell; cell lineage; differentiation; islet; plasticity
AbstractCultured human islets can be dedifferentiated to duct-like structures composed mainly of cytokeratin⁺ and nestin⁺ cells. Given that these structures possess the potential to redifferentiate into islet-like structures, we sought to elucidate their specific cellular origins. Adenoviral vectors were engineered for β-, α-, δ- or PP-cell-specific GFP expression. A doublestranded system was designed whereby cultures were infected with two vectors: one expressed GFP behind the cumateinducible promoter sequence, and the other expressed the requisite transactivator behind the human insulin, glucagon, somatostatin or pancreatic polypeptide promoter. This system labels hormone⁺ cells in the islet in a cell-specific manner, allowing these cells to be tracked during the course of transformation from islet to duct-like structure. Post-infection, islets were cultured to induce dedifferentiation. Fluorescence microscopy demonstrated that α-, δ- and PP-cells contributed equally to the cytokeratin⁺ population, with minimal b-cell contribution, whereas the converse was true for nestin⁺ cells. Complementary targeted cell ablation studies, using streptozotocin or similar adenoviral expression of the Bax (Bcl2-associated X protein) toxigene, validated these findings and suggested a redundancy between α-, δ- and PP-cells with respect to cytokeratin⁺ cell derivation. These results call into question the traditional understanding of islet cells as being terminally differentiated and provide support for the concept of adult islet morphogenetic plasticity.
Publication date
AffiliationNational Research Council Canada; NRC Biotechnology Research Institute
Peer reviewedNo
NRC number47821
NPARC number12400991
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Record identifierb2af08c2-71f7-48fc-84a0-caef01002aa4
Record created2009-10-26
Record modified2016-05-09
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