Neurogenin3 Is Sufficient for Transdetermination of Hepatic Progenitor Cells into Neo-Islets In Vivo but Not Transdifferentiation of Hepatocytes
| Autor: | Antoni Paul, Hideto Kojima, Vijay Yechoor, Lawrence Chan, Kazuhiro Oka, Victoria Liu, Christie Espiritu |
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| Jazyk: | angličtina |
| Předmět: |
medicine.medical_specialty
geography endocrine system geography.geographical_feature_category Cellular differentiation Cell Transdifferentiation DEVBIO Cell Biology Biology Islet STEMCELL General Biochemistry Genetics and Molecular Biology Cell biology medicine.anatomical_structure Endocrinology Internal medicine Cell Transdifferentiation medicine Stem cell Progenitor cell Molecular Biology Transcription factor Developmental Biology |
| Zdroj: | Developmental Cell. (3):358-373 |
| ISSN: | 1534-5807 |
| DOI: | 10.1016/j.devcel.2009.01.012 |
| Popis: | Summary The transcription factor Neurogenin3 (Ngn3) is required for islet-cell type specification. Here, we show that hepatic gene transfer of Ngn3 transiently induces insulin in terminally differentiated hepatocytes but fails to transdifferentiate them, i.e., switch their lineage into islet cells. However, Ngn3 leads to long-term diabetes reversal in mice due to the emergence of periportal islet-like cell clusters. These neo-islets display glycemia-regulated insulin, β-cell-specific transcripts, and an islet-specific transcription cascade, and they produce all four major islet hormones. They appear to arise from hepatic progenitor cells, most likely endoderm-derived oval cells. Thus, transfer of a single lineage-defining transcription factor, Ngn3, is sufficient to induce cell-lineage switching from a hepatic to an islet lineage in these progenitor cells, a process consistent with transdetermination, i.e, lineage switching in lineage-determined, but not terminally differentiated, cells. This paradigm of induced transdetermination of receptive progenitor cells in vivo may be generally applicable to therapeutic organogenesis for multiple diseases, including diabetes. |
| Databáze: | OpenAIRE |
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