ArticleStem cell reports2015
PDX1 binds and represses hepatic genes to ensure robust pancreatic commitment in differentiating human embryonic stem cells.
Article in Stem cell reports, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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Who cites it
27 citing papers in PubMed, 52 citations in OpenAlex.
- Integrative Mapping of Regulatory Variation in African American Hepatocytes Using Colocalization and MPRA: Toward Precision Drug Response.Research square · 2026Article
- Application and challenge of pancreatic organoids in therapeutic research.Frontiers in pharmacology · 2024Review
- Article
- A PDX1 cistrome and single-cell transcriptome resource of the developing pancreas.Development (Cambridge, England) · 2022Article
- Loss of TBX3 enhances pancreatic progenitor generation from human pluripotent stem cells.Stem cell reports · 2021Article
- Interspecies chimeras as a platform for exogenic organ production and transplantation.Experimental biology and medicine (Maywood, N.J.) · 2021Review
- Generation of Hepatobiliary Cell Lineages from Human Induced Pluripotent Stem Cells: Applications in Disease Modeling and Drug Screening.International journal of molecular sciences · 2021Review
- Protocol for the generation of pancreatic and hepatic progenitors from human pluripotent stem cells for gene regulatory assays.STAR protocols · 2021Article
- Evidence from oyster suggests an ancient role for Pdx in regulating insulin gene expression in animals.Nature communications · 2021Article
- A 3D system to model human pancreas development and its reference single-cell transcriptome atlas identify signaling pathways required for progenitor expansion.Nature communications · 2021Article
- Modeling different types of diabetes using human pluripotent stem cells.Cellular and molecular life sciences : CMLS · 2021Review
- NKX6.1 transcription factor: a crucial regulator of pancreatic β cell development, identity, and proliferation.Stem cell research & therapy · 2020Review
- Direct Lineage Reprogramming: Harnessing Cell Plasticity between Liver and Pancreas.Cold Spring Harbor perspectives in biology · 2020Review
- Dynamic proteome profiling of human pluripotent stem cell-derived pancreatic progenitors.Stem cells (Dayton, Ohio) · 2020Article
- Human stem cell models: lessons for pancreatic development and disease.Genes & development · 2019Review
- HNF4A Haploinsufficiency in MODY1 Abrogates Liver and Pancreas Differentiation from Patient-Derived Induced Pluripotent Stem Cells.iScience · 2019Article
- GATA6 Cooperates with EOMES/SMAD2/3 to Deploy the Gene Regulatory Network Governing Human Definitive Endoderm and Pancreas Formation.Stem cell reports · 2019Article
- Genome-wide analysis of PDX1 target genes in human pancreatic progenitors.Molecular metabolism · 2018Article
- Enhanced differentiation of human pluripotent stem cells into pancreatic progenitors co-expressing PDX1 and NKX6.1.Stem cell research & therapy · 2018Article
- Combinations of Activin A or Nicotinamide with the Pancreatic Transcription Factor PDX1 Support Differentiation of Human Amnion Epithelial Cells Toward a Pancreatic Lineage.Cellular reprogramming · 2017Article
Corrections and comments
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Authors and funding
7 authors at 3 institutions in 2 countries.
Funding
Abstract
Inactivation of the Pancreatic and Duodenal Homeobox 1 (PDX1) gene causes pancreatic agenesis, which places PDX1 high atop the regulatory network controlling development of this indispensable organ. However, little is known about the identity of PDX1 transcriptional targets. We simulated pancreatic development by differentiating human embryonic stem cells (hESCs) into early pancreatic progenitors and subjected this cell population to PDX1 chromatin immunoprecipitation sequencing (ChIP-seq). We identified more than 350 genes bound by PDX1, whose expression was upregulated on day 17 of differentiation. This group included known PDX1 targets and many genes not previously linked to pancreatic development. ChIP-seq also revealed PDX1 occupancy at hepatic genes. We hypothesized that simultaneous PDX1-driven activation of pancreatic and repression of hepatic programs underlie early divergence between pancreas and liver. In HepG2 cells and differentiating hESCs, we found that PDX1 binds and suppresses expression of endogenous liver genes. These findings rebrand PDX1 as a context-dependent transcriptional repressor and activator within the same cell type.
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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.