ArticlePLoS genetics2013
Regulation of Neurod1 contributes to the lineage potential of Neurogenin3+ endocrine precursor cells in the pancreas.
Article in PLoS genetics, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers.
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Who cites it
42 citing papers in PubMed, 74 citations in OpenAlex.
- An optimized protocol for efficient derivation of pancreatic islets from multiple human pluripotent stem cell lines.Stem cell reports · 2026Article
- Genome-wide cell type-specific and sex-specific transcriptional dysregulation in the islet of Langerhans underlies islet dysfunction in Down syndrome-related diabetes.bioRxiv : the preprint server for biology · 2026Article
- Enhancement of functional insulin-producing cell differentiation from embryonic stem cells through MST1-silencing.Diabetology & metabolic syndrome · 2025Article
- NKX2.2 and KLF4 cooperate to regulate α-cell identity.Genes & development · 2025Article
- A Translational Regulatory Mechanism Mediated by Hypusinated Eukaryotic Initiation Factor 5A Facilitates β-Cell Identity and Function.Diabetes · 2024Article
- NEUROD1: transcriptional and epigenetic regulator of human and mouse neuronal and endocrine cell lineage programs.Frontiers in cell and developmental biology · 2024Review
- NEUROD1 reinforces endocrine cell fate acquisition in pancreatic development.Nature communications · 2023Article
- Single cell multiomic analysis reveals diabetes-associated β-cell heterogeneity driven by HNF1A.Nature communications · 2023Article
- Inferring regulators of cell identity in the human adult pancreas.NAR genomics and bioinformatics · 2023Article
- Not the second fiddle: α cell development, identity, and function in health and diabetes.The Journal of endocrinology · 2023Review
- Characterization of cell-fate decision landscapes by estimating transcription factor dynamics.Cell reports methods · 2023Article
- Disease-causing mutations in genes encoding transcription factors critical for photoreceptor development.Frontiers in molecular neuroscience · 2023Review
- Feline Adipose Derived Multipotent Stromal Cell Transdifferentiation Into Functional Insulin Producing Cell Clusters.Frontiers in bioengineering and biotechnology · 2022Article
- Emerging Treatment Strategies for Diabetes Mellitus and Associated Complications: An Update.Pharmaceutics · 2021Review
- Pancreatic Progenitor Commitment Is Marked by an Increase in Ink4a/Arf Expression.Biomolecules · 2021Article
- NEUROD1 Is Required for the Early α and β Endocrine Differentiation in the Pancreas.International journal of molecular sciences · 2021Article
- Deoxyhypusine synthase, an essential enzyme for hypusine biosynthesis, is required for proper exocrine pancreas development.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2021Article
- Groucho co-repressor proteins regulate β cell development and proliferation by repressingDevelopment (Cambridge, England) · 2021Article
- A Specialized Niche in the Pancreatic Microenvironment Promotes Endocrine Differentiation.Developmental cell · 2020Article
- Hypusinated eIF5A is expressed in the pancreas and spleen of individuals with type 1 and type 2 diabetes.PloS one · 2020Article
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
Abstract
During pancreatic development, transcription factor cascades gradually commit precursor populations to the different endocrine cell fate pathways. Although mutational analyses have defined the functions of many individual pancreatic transcription factors, the integrative transcription factor networks required to regulate lineage specification, as well as their sites of action, are poorly understood. In this study, we investigated where and how the transcription factors Nkx2.2 and Neurod1 genetically interact to differentially regulate endocrine cell specification. In an Nkx2.2 null background, we conditionally deleted Neurod1 in the Pdx1+ pancreatic progenitor cells, the Neurog3+ endocrine progenitor cells, or the glucagon+ alpha cells. These studies determined that, in the absence of Nkx2.2 activity, removal of Neurod1 from the Pdx1+ or Neurog3+ progenitor populations is sufficient to reestablish the specification of the PP and epsilon cell lineages. Alternatively, in the absence of Nkx2.2, removal of Neurod1 from the Pdx1+ pancreatic progenitor population, but not the Neurog3+ endocrine progenitor cells, restores alpha cell specification. Subsequent in vitro reporter assays demonstrated that Nkx2.2 represses Neurod1 in alpha cells. Based on these findings, we conclude that, although Nkx2.2 and Neurod1 are both necessary to promote beta cell differentiation, Nkx2.2 must repress Neurod1 in a Pdx1+ pancreatic progenitor population to appropriately commit a subset of Neurog3+ endocrine progenitor cells to the alpha cell lineage. These results are consistent with the proposed idea that Neurog3+ endocrine progenitor cells represent a heterogeneous population of unipotent cells, each restricted to a particular endocrine lineage.
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