ArticleDevelopmental cell2009
Neurogenin3 is sufficient for transdetermination of hepatic progenitor cells into neo-islets in vivo but not transdifferentiation of hepatocytes.
Article in Developmental cell, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 94 papers.
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Who cites it
94 citing papers in PubMed, 178 citations in OpenAlex.
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- Stem Cells Reprogramming in Diabetes Mellitus and Diabetic Complications: Recent Advances.Current diabetes reviews · 2025Review
- Enhancer landscape of lung neuroendocrine tumors reveals regulatory and developmental signatures with potential theranostic implications.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Direct reprogramming of human fibroblasts into insulin-producing cells using transcription factors.Communications biology · 2023Article
- Hepatic insulin synthesis increases in rat models of diabetes mellitus type 1 and 2 differently.PloS one · 2023Article
- Direct Reprogramming of Somatic Cells into Induced β-Cells: An Overview.Advances in experimental medicine and biology · 2023Article
- Pancreatic Transdifferentiation Using β-Cell Transcription Factors for Type 1 Diabetes Treatment.Cells · 2022Review
- Molecular mechanisms of transcription factor mediated cell reprogramming: conversion of liver to pancreas.Biochemical Society transactions · 2021Review
- Neonatal diabetes mutations disrupt a chromatin pioneering function that activates the human insulin gene.Cell reports · 2021Article
- Direct Lineage Reprogramming: Harnessing Cell Plasticity between Liver and Pancreas.Cold Spring Harbor perspectives in biology · 2020Review
- Vector-free in vivo trans-determination of adult hepatic stem cells to insulin-producing cells.Molecular biology reports · 2019Article
- Liver to Pancreas Transdifferentiation.Current diabetes reports · 2019Review
- Long-Term Correction of Diabetes in Mice by In Vivo Reprogramming of Pancreatic Ducts.Molecular therapy : the journal of the American Society of Gene Therapy · 2018Article
- PDX1, Neurogenin-3, and MAFA: critical transcription regulators for beta cell development and regeneration.Stem cell research & therapy · 2017Review
- Regenerative medicine and cell-based approaches to restore pancreatic function.Nature reviews. Gastroenterology & hepatology · 2017Review
- Anti-TCRβ mAb in Combination With Neurogenin3 Gene Therapy Reverses Established Overt Type 1 Diabetes in Female NOD Mice.Endocrinology · 2017Article
- A mouse tissue transcription factor atlas.Nature communications · 2017Article
- Stepwise reprogramming of liver cells to a pancreas progenitor state by the transcriptional regulator Tgif2.Nature communications · 2017Article
- Article
34 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 2 countries.
Funding
Abstract
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, beta-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.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.