ArticleNature communications2019
Sufu- and Spop-mediated downregulation of Hedgehog signaling promotes beta cell differentiation through organ-specific niche signals.
Article in Nature communications, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers, 2 of them syntheses that pooled it.
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The trial behind it
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Who cites it
23 citing papers in PubMed, 2 syntheses or guidelines pooled it, 44 citations in OpenAlex.
- Shared genetic effect of kidney function on bipolar and major depressive disorders: a large-scale genome-wide cross-trait analysis.Human genomics · 2024Pooled it
- Manipulation of Sonic Hedgehog Signaling Pathway in Maintenance, Differentiation, and Endocrine Activity of Insulin-Producing Cells: A Systematic Review.Iranian journal of medical sciences · 2024Pooled it
- Understanding development and cellular plasticity in the pancreas in health and disease.Nature reviews. Gastroenterology & hepatology · 2026Review
- Fuel to fire: developmental niche-empowered ApoEVs unlock adult hierarchical tissue regenerative potential via mitochondrial complex I-driven developmental metabolic profile.International journal of oral science · 2026Article
- Tankyrase inhibition promotes endocrine commitment of hPSC-derived pancreatic progenitors.Nature communications · 2024Article
- Heterozygous missense variant in GLI2 impairs human endocrine pancreas development.Nature communications · 2024Article
- The Role of G Protein-Coupled Receptors and Receptor Kinases in PancreaticPharmacological reviews · 2024Review
- Disrupting Hedgehog signaling in melanocytes by SUFU knockout leads to ocular melanocytosis and anterior segment malformation.Disease models & mechanisms · 2023Article
- Ultrasound-guided fine-needle aspiration/biopsy-based pancreatic organoids establishment: an alternative model for basic and preclinical research.Gastroenterology report · 2023Review
- Maturation of beta cells: lessons from in vivo and in vitro models.Diabetologia · 2022Review
- Human pancreatic microenvironment promotes β-cell differentiation via non-canonical WNT5A/JNK and BMP signaling.Nature communications · 2022Article
- Development of a 3D atlas of the embryonic pancreas for topological and quantitative analysis of heterologous cell interactions.Development (Cambridge, England) · 2022Article
- Suppressor of fused-restrained Hedgehog signaling in chondrocytes is critical for epiphyseal growth plate maintenance and limb elongation in juvenile mice.Frontiers in cell and developmental biology · 2022Article
- Improved Differentiation of hESC-Derived Pancreatic Progenitors by Using Human Fetal Pancreatic Mesenchymal Cells in a Micro-scalable Three-Dimensional Co-culture System.Stem cell reviews and reports · 2022Article
- Pancreatic cell fate specification: insights into developmental mechanisms and their application for lineage reprogramming.Current opinion in genetics & development · 2021Review
- A pancreas tumor derived organoid study: from drug screen to precision medicine.Cancer cell international · 2021Review
- Ultrafiltration and Injection of Islet Regenerative Stimuli Secreted by Pancreatic Mesenchymal Stromal Cells.Stem cells and development · 2021Article
- Gene regulatory network inference as relaxed graph matching.Proceedings of the ... AAAI Conference on Artificial Intelligence. AAAI Conference on Artificial Intelligence · 2021Article
- Harnessing Proliferation for the Expansion of Stem Cell-Derived Pancreatic Cells: Advantages and Limitations.Frontiers in endocrinology · 2021Review
- SPOP and CUL3 Modulate the Sonic Hedgehog Signal Response Through Controlled Degradation of GLI Family Transcription Factors.Frontiers in cell and developmental biology · 2021Review
Corrections and comments
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
Abstract
Human embryonic stem cell-derived beta cells offer a promising cell-based therapy for diabetes. However, efficient stem cell to beta cell differentiation has proven difficult, possibly due to the lack of cross-talk with the appropriate mesenchymal niche. To define organ-specific niche signals, we isolated pancreatic and gastrointestinal stromal cells, and analyzed their gene expression during development. Our genetic studies reveal the importance of tightly regulated Hedgehog signaling in the pancreatic mesenchyme: inactivation of mesenchymal signaling leads to annular pancreas, whereas stroma-specific activation of signaling via loss of Hedgehog regulators, Sufu and Spop, impairs pancreatic growth and beta cell genesis. Genetic rescue and transcriptome analyses show that these Sufu and Spop knockout defects occur through Gli2-mediated activation of gastrointestinal stromal signals such as Wnt ligands. Importantly, inhibition of Wnt signaling in organoid and human stem cell cultures significantly promotes insulin-producing cell generation, altogether revealing the requirement for organ-specific regulation of stromal niche signals.
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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.