ArticlePLoS genetics2013
Nkx6.1 controls a gene regulatory network required for establishing and maintaining pancreatic Beta cell identity.
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 142 papers.
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Who cites it
142 citing papers in PubMed, 250 citations in OpenAlex.
- The comparative cell physiology of stem cell-derived and primary human β cells.Nature reviews. Endocrinology · 2026Review
- Article
- Efficient control of enterochromaffin versus islet differentiation from human pluripotent stem cell-derived pancreatic progenitors.Nature communications · 2026Article
- Chicoric acid-rich extract ofFrontiers in pharmacology · 2026Article
- BMP5 signalling in beta cells and the impact on insulin secretion in the context of type 2 diabetes.Diabetologia · 2025Article
- Sex-specific astrocyte regulation of spinal motor circuits by Nkx6.1.Cell reports · 2025Article
- Post translational modification regulation of transcription factors governing pancreatic β-cell identity and functional mass.Frontiers in endocrinology · 2025Review
- Advancing diabetes management: Exploring pancreatic beta-cell restoration's potential and challenges.World journal of gastroenterology · 2024Review
- Generation of a pancreas derived hydrogel for the culture of hiPSC derived pancreatic endocrine cells.Scientific reports · 2024Article
- Targeting β-Cell Plasticity: A Promising Approach for Diabetes Treatment.Current issues in molecular biology · 2024Review
- Pump-Less, Recirculating Organ-on-Chip (rOoC) Platform to Model the Metabolic Crosstalk between Islets and Liver.Advanced healthcare materials · 2024Article
- IAPP Marks Mono-hormonal Stem-cell Derived β Cells that Maintain Stable Insulin ProductionbioRxiv : the preprint server for biology · 2024Article
- Article
- β-Cell Regeneration Is Driven by Pancreatic Plasticity.Advances in anatomy, embryology, and cell biology · 2024Review
- Characterization of cell-fate decision landscapes by estimating transcription factor dynamics.Cell reports methods · 2023Article
- Deficiency of WTAP in islet beta cells results in beta cell failure and diabetes in mice.Diabetologia · 2023Article
- Major β cell-specific functions of NKX2.2 are mediated via the NK2-specific domain.Genes & development · 2023Article
- p53 Inhibition in Pancreatic Progenitors Enhances the Differentiation of Human Pluripotent Stem Cells into Pancreatic β-Cells.Stem cell reviews and reports · 2023Article
- Presence of immunogenic alternatively spliced insulin gene product in human pancreatic delta cells.Diabetologia · 2023Article
- Human pluripotent stem cell-derived β cells: Truly immature islet β cells for type 1 diabetes therapy?World journal of stem cells · 2023Review
82 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
12 authors at 5 institutions in 2 countries.
Funding
Abstract
All pancreatic endocrine cell types arise from a common endocrine precursor cell population, yet the molecular mechanisms that establish and maintain the unique gene expression programs of each endocrine cell lineage have remained largely elusive. Such knowledge would improve our ability to correctly program or reprogram cells to adopt specific endocrine fates. Here, we show that the transcription factor Nkx6.1 is both necessary and sufficient to specify insulin-producing beta cells. Heritable expression of Nkx6.1 in endocrine precursors of mice is sufficient to respecify non-beta endocrine precursors towards the beta cell lineage, while endocrine precursor- or beta cell-specific inactivation of Nkx6.1 converts beta cells to alternative endocrine lineages. Remaining insulin(+) cells in conditional Nkx6.1 mutants fail to express the beta cell transcription factors Pdx1 and MafA and ectopically express genes found in non-beta endocrine cells. By showing that Nkx6.1 binds to and represses the alpha cell determinant Arx, we identify Arx as a direct target of Nkx6.1. Moreover, we demonstrate that Nkx6.1 and the Arx activator Isl1 regulate Arx transcription antagonistically, thus establishing competition between Isl1 and Nkx6.1 as a critical mechanism for determining alpha versus beta cell identity. Our findings establish Nkx6.1 as a beta cell programming factor and demonstrate that repression of alternative lineage programs is a fundamental principle by which beta cells are specified and maintained. Given the lack of Nkx6.1 expression and aberrant activation of non-beta endocrine hormones in human embryonic stem cell (hESC)-derived insulin(+) cells, our study has significant implications for developing cell replacement therapies.
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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.