ArticlePloS one2015
The Role of ARX in Human Pancreatic Endocrine Specification.
Article in PloS one, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers, 1 of them a synthesis that pooled it.
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Who cites it
23 citing papers in PubMed, 1 synthesis or guideline pooled it, 47 citations in OpenAlex.
- Generation of human islet cell type-specific identity genesets.Nature communications · 2022Pooled it
- Resolving human α versus β cell fate allocation for the generation of stem cell-derived islets.Nature communications · 2026Article
- Comparative β-cell development: insights from Rodents, humans and induced pluripotent stem cell models.Stem cell research & therapy · 2025Review
- Single-cell transcriptomics of human organoid-derived enteroendocrine cell populations from the small intestine.The Journal of physiology · 2025Article
- Liver-specific glucagon dysfunction promotes PP-cell hyperplasia and formation of glucagon and PP double-positive cells.PloS one · 2025Article
- Pancreatic Differentiation of Oral Minor Salivary Gland Stem Cells.Stem cell reviews and reports · 2024Article
- Functional interrogation of twenty type 2 diabetes-associated genes using isogenic human embryonic stem cell-derived β-like cells.Cell metabolism · 2023Article
- PAX4 loss of function increases diabetes risk by altering human pancreatic endocrine cell development.Nature communications · 2023Article
- Intertumoral lineage diversity and immunosuppressive transcriptional programs in well-differentiated gastroenteropancreatic neuroendocrine tumors.Science advances · 2023Article
- Characterization of cell-fate decision landscapes by estimating transcription factor dynamics.Cell reports methods · 2023Article
- The Haematopoietically-expressed homeobox transcription factor: roles in development, physiology and disease.Frontiers in immunology · 2023Review
- The Human Islet: Mini-Organ With Mega-Impact.Endocrine reviews · 2021Review
- Human Pluripotent Stem Cells to Model Islet Defects in Diabetes.Frontiers in endocrinology · 2021Review
- Loss of the transcription factor MAFB limits β-cell derivation from human PSCs.Nature communications · 2020Article
- NovelHuman genome variation · 2020Article
- BERMUDA: a novel deep transfer learning method for single-cell RNA sequencing batch correction reveals hidden high-resolution cellular subtypes.Genome biology · 2019Article
- FOXA2 Is Required for Enhancer Priming during Pancreatic Differentiation.Cell reports · 2019Article
- Concise Review: Human Pluripotent Stem Cells for the Modeling of Pancreatic β-Cell Pathology.Stem cells (Dayton, Ohio) · 2019Review
- SIRT1 activation attenuates α cell hyperplasia, hyperglucagonaemia and hyperglycaemia in STZ-diabetic mice.Scientific reports · 2018Article
- Mutant Mice With Calcium-Sensing Receptor Activation Have Hyperglycemia That Is Rectified by Calcilytic Therapy.Endocrinology · 2017Article
Corrections and comments
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Authors and funding
10 authors at 5 institutions in 2 countries.
Funding
Abstract
The in vitro differentiation of human embryonic stem cells (hESCs) offers a model system to explore human development. Humans with mutations in the transcription factor Aristaless Related Homeobox (ARX) often suffer from the syndrome X-linked lissencephaly with ambiguous genitalia (XLAG), affecting many cell types including those of the pancreas. Indeed, XLAG pancreatic islets lack glucagon and pancreatic polypeptide-positive cells but retain somatostatin, insulin, and ghrelin-positive cells. To further examine the role of ARX in human pancreatic endocrine development, we utilized genomic editing in hESCs to generate deletions in ARX. ARX knockout hESCs retained pancreatic differentiation capacity and ARX knockout endocrine cells were biased toward somatostatin-positive cells (94% of endocrine cells) with reduced pancreatic polypeptide (rarely detected), glucagon (90% reduced) and insulin-positive (65% reduced) lineages. ARX knockout somatostatin-positive cells shared expression patterns with human fetal and adult δ-cells. Differentiated ARX knockout cells upregulated PAX4, NKX2.2, ISL1, HHEX, PCSK1, PCSK2 expression while downregulating PAX6 and IRX2. Re-expression of ARX in ARX knockout pancreatic progenitors reduced HHEX and increased PAX6 and insulin expression following differentiation. Taken together these data suggest that ARX plays a key role in pancreatic endocrine fate specification of pancreatic polypeptide, somatostatin, glucagon and insulin positive cells from hESCs.
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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.