ArticleNature communications2024
Identification of unique cell type responses in pancreatic islets to stress.
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Article in Nature communications, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers.
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Who cites it
42 citing papers in PubMed.
- Interleukin-1 mediates innate immune signaling and antiviral defense in islets.Life science alliance · 2026Article
- ProtectiveiScience · 2026Article
- Article
- Applications of Stem Cell-Derived Islets and Emerging Experimental Platforms to Understand Diabetes.Diabetes · 2026Review
- Temporal single-cell transcriptional dynamics of murine pancreatic islet remodeling during hyperglycaemia progression.Molecular metabolism · 2026Article
- Differential immune- and apoptosis-related gene signatures in pancreatic alpha and beta cells contribute to their fate in type 1 diabetes.Cell death and differentiation · 2026Article
- From Disposal to Display: Crinophagy as a β-Cell Source of Neoantigens in Type 1 Diabetes.Immunological reviews · 2026Review
- Human pancreatic ductal cells from non-diabetic donors function as non-professional antigen-presenting cells upon inflammatory cytokine exposure.Diabetologia · 2026Article
- Protocol to stress human primary pancreatic islets with diabetogenic factors for subsequent single-cell RNA sequencing.STAR protocols · 2026Article
- Condition-Associated Pattern Extraction and Recovery From Multi-Condition Single-Cell RNA-seq Data With CAPER.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- A dish-to-biobank framework links β-cell nutrient-stress programs to genetic and dietary risk for Type 2 Diabetes.bioRxiv : the preprint server for biology · 2026Article
- Regenerative macrophages enhance stem cell-derived β cell function and engraftment.Science advances · 2026Article
- Sensing and Communicating β-Cell Stress in the Context of T1D Etiology: New Opportunities for Therapeutic Impact.Comprehensive Physiology · 2026Review
- Deep single-cell decoding of human pancreatic islets reveals T2D β-cell gene expression defects.The EMBO journal · 2026Article
- A surviving beta cell subpopulation enriched in patients with T1D.bioRxiv : the preprint server for biology · 2026Article
- Divergent cell-type specific hypoxia responses in human stem cell-derived and primary islets.Scientific reports · 2026Article
- From bats to humans: uncoveringbioRxiv : the preprint server for biology · 2026Article
- Functional genomics reveals mediators of beta cell survival in ER stress and type 2 diabetes risk.bioRxiv : the preprint server for biology · 2026Article
- Whole-genome CRISPR screening identifies genetic modifiers of stem cell-derived islet transplantation.Stem cells translational medicine · 2026Article
- Beta cell-derived cholecystokinin drives obesity-associated pancreatic adenocarcinoma development.Nature communications · 2026Article
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Authors and funding
12 authors.
Marlie M MaestasRoy and Diana Vagelos Division of Biology and Biomedical Sciences, Washington University School of Medicine, MSC 8127-057-08, 660 South Euclid Avenue, St. Louis, MO, 63110, USA.
Matthew IshahakDivision of Endocrinology, Metabolism, and Lipid Research, Washington University School of Medicine, MSC 8127-057-08, St. Louis, USA.ORCID 0000-0002-7494-6048
Punn AugsornworawatDepartment of Immunology, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, 10700, Thailand.ORCID 0000-0001-8602-5433
Daniel A Veronese-PaniaguaRoy and Diana Vagelos Division of Biology and Biomedical Sciences, Washington University School of Medicine, MSC 8127-057-08, 660 South Euclid Avenue, St. Louis, MO, 63110, USA.
Kristina G MaxwellDivision of Endocrinology, Metabolism, and Lipid Research, Washington University School of Medicine, MSC 8127-057-08, St. Louis, USA.ORCID 0000-0003-0869-1662
Leonardo Velazco-CruzRoy and Diana Vagelos Division of Biology and Biomedical Sciences, Washington University School of Medicine, MSC 8127-057-08, 660 South Euclid Avenue, St. Louis, MO, 63110, USA.
Erica MarquezDivision of Endocrinology, Metabolism, and Lipid Research, Washington University School of Medicine, MSC 8127-057-08, St. Louis, USA.
Jiameng SunRoy and Diana Vagelos Division of Biology and Biomedical Sciences, Washington University School of Medicine, MSC 8127-057-08, 660 South Euclid Avenue, St. Louis, MO, 63110, USA.
Mira ShunkarovaDivision of Endocrinology, Metabolism, and Lipid Research, Washington University School of Medicine, MSC 8127-057-08, St. Louis, USA.
Sarah E GaleDivision of Endocrinology, Metabolism, and Lipid Research, Washington University School of Medicine, MSC 8127-057-08, St. Louis, USA.
Fumihiko UranoRoy and Diana Vagelos Division of Biology and Biomedical Sciences, Washington University School of Medicine, MSC 8127-057-08, 660 South Euclid Avenue, St. Louis, MO, 63110, USA.ORCID 0000-0002-9944-6293
Jeffrey R MillmanRoy and Diana Vagelos Division of Biology and Biomedical Sciences, Washington University School of Medicine, MSC 8127-057-08, 660 South Euclid Avenue, St. Louis, MO, 63110, USA. jmillman@wustl.edu.ORCID 0000-0003-0426-3492
Funding
Washington University Center for Cellular ImagingP30CA091842 · NCI · WASHINGTON UNIVERSITY · PI TIMOTHY J. EBERLEIN · 2001 to 2026
$128.0MWU INSTITUTE OF CLINICAL AND TRANSLATIONAL SCIENCESUL1TR002345 · NCATS · WASHINGTON UNIVERSITY · PI William G. Powderly · 2017 to 2026
$97.8MWU P&FP30DK020579 · NIDDK · WASHINGTON UNIVERSITY · PI Clay F. Semenkovich · 2013 to 2026
$27.1MTRANSGENICS COREP60DK020579 · NIDDK · WASHINGTON UNIVERSITY · PI SCHAFFER, JEAN E. · 1986 to 2012
$25.2MThe Human Pancreas Analysis Program for Type 2 DiabetesU01DK123594 · NIDDK · UNIVERSITY OF PENNSYLVANIA · PI Robert Babak Faryabi, KLAUS H KAESTNER · 2019 to 2026
$25.0MPenn integrated Human Pancreas procurement and Analysis ProgramUC4DK112217 · NIDDK · UNIVERSITY OF PENNSYLVANIA · PI BETTS, MICHAEL R, FELDMAN, MICHAEL D · 2016 to 2020
$17.8MDIABETES &RELATED METABOLIC DISEASEST32DK007120 · NIDDK · WASHINGTON UNIVERSITY · PI MARCO COLONNA, Maria Sara Remedi · 1986 to 2026
$15.7MSupplement to Integrated Program for Human Pancreas Procurement and AnalysisUC4DK112232 · NIDDK · VANDERBILT UNIVERSITY MEDICAL CENTER · PI ATKINSON, MARK A., POWERS, ALVIN C · 2016 to 2020
$8.4MTraining Program in Cellular and Molecular BiologyT32GM139774 · NIGMS · WASHINGTON UNIVERSITY · PI HEATHER L TRUE-KROB · 2021 to 2026
$6.7MHuman Pancreas Analysis Program-T2DU01DK123716 · NIDDK · VANDERBILT UNIVERSITY MEDICAL CENTER · PI ATKINSON, MARK A., BOTTINO, RITA · 2019 to 2024
$6.6MDetermining the mechanism of IFIH1 disease-associated variants on beta-cell and immune responses in Type 1 diabetesR01DK127497 · NIDDK · UNIVERSITY OF KANSAS MEDICAL CENTER · PI MATHEWS, CLAYTON E, MILLMAN, JEFFREY ROBERT · 2020 to 2023
$4.7MSTUDYING THE ROLE OF THE MICROENVIRONMENT ON DIFFERENTIATION AND MATURATION OF BETA CELLSR01DK114233 · NIDDK · WASHINGTON UNIVERSITY · PI Jeffrey Robert Millman · 2017 to 2026
$3.6MBreakthrough T1D 3-SRA-2023-1295-S-BNational Science Foundation (NSF) DGE-2139839 and DGE-1745038NCATS NIH HHS UL1 TR002345NCI NIH HHS P30 CA091842NIDDK NIH HHS F31 DK125068NIDDK NIH HHS P30 DK020579NIDDK NIH HHS P60 DK020579NIDDK NIH HHS R01 DK114233NIDDK NIH HHS R01 DK127497NIDDK NIH HHS R01 DK132090NIDDK NIH HHS R01 DK138469NIDDK NIH HHS T32 DK007120NIDDK NIH HHS T32 DK108742NIDDK NIH HHS U01 DK123594NIDDK NIH HHS U01 DK123716NIDDK NIH HHS UC4 DK112217NIDDK NIH HHS UC4 DK112232NIGMS NIH HHS T32 GM139774U.S. Department of Health & Human Services | NIH | National Institute of Diabetes and Digestive and Kidney Diseases (National Institute of Diabetes & Digestive & Kidney Diseases) F31DK125068U.S. Department of Health & Human Services | NIH | National Institute of Diabetes and Digestive and Kidney Diseases (National Institute of Diabetes & Digestive & Kidney Diseases) Human Islet Research Network (HIRN) Catalyst AwardU.S. Department of Health & Human Services | NIH | National Institute of Diabetes and Digestive and Kidney Diseases (National Institute of Diabetes & Digestive & Kidney Diseases) R01DK020579U.S. Department of Health & Human Services | NIH | National Institute of Diabetes and Digestive and Kidney Diseases (National Institute of Diabetes & Digestive & Kidney Diseases) R01DK114233U.S. Department of Health & Human Services | NIH | National Institute of Diabetes and Digestive and Kidney Diseases (National Institute of Diabetes & Digestive & Kidney Diseases) R01DK127497U.S. Department of Health & Human Services | NIH | National Institute of Diabetes and Digestive and Kidney Diseases (National Institute of Diabetes & Digestive & Kidney Diseases) R01DK132090U.S. Department of Health & Human Services | NIH | National Institute of Diabetes and Digestive and Kidney Diseases (National Institute of Diabetes & Digestive & Kidney Diseases) R01DK138469U.S. Department of Health & Human Services | NIH | National Institute of Diabetes and Digestive and Kidney Diseases (National Institute of Diabetes & Digestive & Kidney Diseases) T32DK007120U.S. Department of Health & Human Services | NIH | National Institute of Diabetes and Digestive and Kidney Diseases (National Institute of Diabetes & Digestive & Kidney Diseases) T32DK108742U.S. Department of Health & Human Services | NIH | National Institute of General Medical Sciences (NIGMS) T32GM139774WUSTL | Washington University School of Medicine in St. Louis Rita Levi-Montalcini Postdoctoral Fellowship in Regenerative Medicine
Abstract
Diabetes involves the death or dysfunction of pancreatic β-cells. Analysis of bulk sequencing from human samples and studies using in vitro and in vivo models suggest that endoplasmic reticulum and inflammatory signaling play an important role in diabetes progression. To better characterize cell type-specific stress response, we perform multiplexed single-cell RNA sequencing to define the transcriptional signature of primary human islet cells exposed to endoplasmic reticulum and inflammatory stress. Through comprehensive pair-wise analysis of stress responses across pancreatic endocrine and exocrine cell types, we define changes in gene expression for each cell type under different diabetes-associated stressors. We find that β-, α-, and ductal cells have the greatest transcriptional response. We utilize stem cell-derived islets to study islet health through the candidate gene CIB1, which was upregulated under stress in primary human islets. Our findings provide insights into cell type-specific responses to diabetes-associated stress and establish a resource to identify targets for diabetes therapeutics.
Indexed as
Endoplasmic Reticulum StressInsulin-Secreting CellsIslets of LangerhansCalcium-Binding ProteinsGlucagon-Secreting CellsHumansSequence Analysis, RNASingle-Cell AnalysisStress, PhysiologicalTranscriptomeCalcium-Binding Proteins
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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 Socratic graph.