ArticlePLoS biology2017
Pancreas lineage allocation and specification are regulated by sphingosine-1-phosphate signalling.
Article in PLoS biology, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
What it found
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Who cites it
21 citing papers in PubMed, 33 citations in OpenAlex.
- Role of Sphingosine-1-Phosphate Signaling Pathway in Pancreatic Diseases.International journal of molecular sciences · 2024Review
- Generation and application of novel hES cell reporter lines for the differentiation and maturation of hPS cell-derived islet-like clusters.Scientific reports · 2024Article
- Article
- Review
- Uncovering the 'sphinx' of sphingosine 1-phosphate signalling: from cellular events to organ morphogenesis.Biological reviews of the Cambridge Philosophical Society · 2022Review
- Angiocrine Sphingosine-1-Phosphate Activation of S1PR2-YAP Signaling Axis in Alveolar Type II Cells Is Essential for Lung Repair.Cell reports · 2020Article
- Life-long impairment of glucose homeostasis upon prenatal exposure to psychostimulants.The EMBO journal · 2020Article
- Role of Hippo-YAP1/TAZ pathway and its crosstalk in cardiac biology.International journal of biological sciences · 2020Review
- Sphingosine-1-phosphate induces islet β-cell proliferation and decreases cell apoptosis in high-fat diet/streptozotocin diabetic mice.Experimental and therapeutic medicine · 2019Article
- Bioactive lipids in cancer stem cells.World journal of stem cells · 2019Review
- Hippo signalling during development.Development (Cambridge, England) · 2019Review
- Review
- Protein Methyltransferase Inhibition Decreases Endocrine Specification Through the Upregulation of Aldh1b1 Expression.Stem cells (Dayton, Ohio) · 2019Article
- Defining multistep cell fate decision pathways during pancreatic development at single-cell resolution.The EMBO journal · 2019Article
- Modelling the endocrine pancreas in health and disease.Nature reviews. Endocrinology · 2019Review
- Article
- Modulatory Effects of Fingolimod (FTY720) on the Expression of Sphingolipid Metabolism-Related Genes in an Animal Model of Alzheimer's Disease.Molecular neurobiology · 2019Article
- Effect of Sphingosine-1-Phosphate on Intracellular Free Ca²⁺ in Cat Esophageal Smooth Muscle Cells.Biomolecules & therapeutics · 2018Article
- Regulatory role of sphingosine kinase and sphingosine-1-phosphate receptor signaling in progenitor/stem cells.World journal of stem cells · 2018Review
- Lineage dynamics of murine pancreatic development at single-cell resolution.Nature communications · 2018Article
Corrections and comments
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Authors and funding
8 authors at 7 institutions in 4 countries.
Funding
Abstract
During development, progenitor expansion, lineage allocation, and implementation of differentiation programs need to be tightly coordinated so that different cell types are generated in the correct numbers for appropriate tissue size and function. Pancreatic dysfunction results in some of the most debilitating and fatal diseases, including pancreatic cancer and diabetes. Several transcription factors regulating pancreas lineage specification have been identified, and Notch signalling has been implicated in lineage allocation, but it remains unclear how these processes are coordinated. Using a combination of genetic approaches, organotypic cultures of embryonic pancreata, and genomics, we found that sphingosine-1-phosphate (S1p), signalling through the G protein coupled receptor (GPCR) S1pr2, plays a key role in pancreas development linking lineage allocation and specification. S1pr2 signalling promotes progenitor survival as well as acinar and endocrine specification. S1pr2-mediated stabilisation of the yes-associated protein (YAP) is essential for endocrine specification, thus linking a regulator of progenitor growth with specification. YAP stabilisation and endocrine cell specification rely on Gαi subunits, revealing an unexpected specificity of selected GPCR intracellular signalling components. Finally, we found that S1pr2 signalling posttranscriptionally attenuates Notch signalling levels, thus regulating lineage allocation. Both S1pr2-mediated YAP stabilisation and Notch attenuation are necessary for the specification of the endocrine lineage. These findings identify S1p signalling as a novel key pathway coordinating cell survival, lineage allocation, and specification and linking these processes by regulating YAP levels and Notch signalling. Understanding lineage allocation and specification in the pancreas will shed light in the origins of pancreatic diseases and may suggest novel therapeutic approaches.
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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.