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pmid:37924378
Apolipoprotein L genes are novel mediators of inflammation in beta cells.
Miriam Paz-Barba · Amadeo Muñoz Garcia · Twan J J de Winter · Natascha de Graaf · Maarten van Agen · Elisa van der Sar · Ferdy Lambregtse · Lizanne Daleman · Arno van der Slik · Arnaud Zaldumbide · Eelco J P de Koning · Françoise Carlotti
Diabetologia · 2024 doi:10.1007/s00125-023-06033-z
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Experiment
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Data
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Analysis
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Complete file
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The apolipoprotein L (APOL) family of genes has been associated with innate immunity and apoptosis in non-pancreatic cell types, but also with metabolic syndrome and type 2 diabetes mellitus. Here, we hypothesised that APOL genes play a role in inflammation-induced beta cell damage.\nMETHODS: We used single-cell transcriptomics datasets of primary human pancreatic islet cells to study the expression of APOL genes upon specific stress conditions. Validation of the findings was carried out in EndoC-βH1 cells and primary human islets. Finally, we performed loss- and gain-of-function experiments to investigate the role of APOL genes in beta cells.\nRESULTS: APOL genes are expressed in primary human beta cells and APOL1, 2 and 6 are strongly upregulated upon inflammation via the Janus kinase (JAK)-signal transducer and activator of transcription (STAT) pathway. APOL1 overexpression increases endoplasmic reticulum stress while APOL1 knockdown prevents cytokine-induced beta cell death and interferon-associated response. Furthermore, we found that APOL genes are upregulated in beta cells from donors with type 2 diabetes compared with donors without diabetes mellitus.\nCONCLUSIONS/INTERPRETATION: APOLs are novel regulators of islet inflammation and may contribute to beta cell damage during the development of diabetes.\nDATA AVAILABILITY: scRNAseq data generated by our laboratory and used in this study are available in the Gene Expression Omnibus (GEO; www.ncbi.nlm.nih.gov/geo/ ), accession number GSE218316.", "claims": [{"id": "claim-method", "statement": "We used our single-cell RNA-sequencing Gene Expression Omnibus (GEO; www.ncbi.nlm.nih.gov/geo/) dataset generated from human pancreatic islets treated with beta cell stressors (GSE218316) and performed a differential gene expression analysis of human islet cells treated with IL-1β + IFNγ using a Wilcoxon rank-sum test.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:37924378", "locator": "sections[5] \"Single-cell RNA-sequencing\" paragraph 2", "quote": "We used our single-cell RNA-sequencing Gene Expression Omnibus (GEO; www.ncbi.nlm.nih.gov/geo/) dataset generated from human pancreatic islets treated with beta cell stressors (GSE218316) and performed a differential gene expression analysis of human islet cells treated with IL-1β + IFNγ using a Wilcoxon rank-sum test."}], "state": "complete"}, {"id": "claim-data-access", "statement": "scRNAseq data generated by our laboratory and used in this study are available in the Gene Expression Omnibus (GEO; www.ncbi.nlm.nih.gov/geo/), accession number GSE218316.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:37924378", "locator": "sections[0] \"Abstract\" paragraph 5", "quote": "scRNAseq data generated by our laboratory and used in this study are available in the Gene Expression Omnibus (GEO; www.ncbi.nlm.nih.gov/geo/), accession number GSE218316."}], "state": "complete"}, {"id": "claim-target-result", "statement": "APOLs are novel regulators of islet inflammation and may contribute to beta cell damage during the development of diabetes.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:37924378", "locator": "sections[0] \"Abstract\" paragraph 4", "quote": "APOLs are novel regulators of islet inflammation and may contribute to beta cell damage during the development of diabetes."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "partial", "objective": "APOLs are novel regulators of islet inflammation and may contribute to beta cell damage during the development of diabetes.", "steps": [{"id": "read_published_estimate", "order": 1, "name": "Read the published estimate from the source", "kind": "other", "state": "complete", "blocked_on": null, "description": "The claim, method and evidence span published with the source article.", "duration_hours": null, "parameters": {}, "inputs": ["source:pmid:37924378"], "outputs": ["the published estimate and its evidence"], "instruments": [], "reagents": []}, {"id": "obtain_source_data", "order": 2, "name": "Obtain the source data from the named repository", "kind": "data-preparation", "state": "complete", "blocked_on": null, "description": "The GEO series accession resolves and its sample accessions are listed. 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"GSM2172371", "GSM2172372", "GSM2172373", "GSM2172374", "GSM2172375", "GSM2172376", "GSM2172377", "GSM2172378", "GSM2172379", "GSM2172380", "GSM2172381", "GSM2172382", "GSM2172383", "GSM2172384", "GSM2172385", "GSM2172386", "GSM2172387", "GSM2172388", "GSM2172389", "GSM2172390", "GSM2172391", "GSM2172392", "GSM2172393", "GSM2172394", "GSM2172395", "GSM2172396", "GSM2172397", "GSM2172398", "GSM2172399", "GSM2172400", "GSM2172401", "GSM2172402", "GSM2172403", "GSM2172404", "GSM2172405", "GSM2172406", "GSM2172407", "GSM2172408", "GSM2172409", "GSM2172410", "GSM2172411", "GSM2172412", "GSM2172413", "GSM2172414", "GSM2172415", "GSM2172416", "GSM2172417", "GSM2172418", "GSM2172419", "GSM2172420", "GSM2172421", "GSM2172422", "GSM2172423", "GSM2172424", "GSM2172425", "GSM2172426", "GSM2172427", "GSM2172428", "GSM2172429", "GSM2172430", "GSM2172431", "GSM2172432", "GSM2172433", "GSM2172434", "GSM2172435", "GSM2172436", "GSM2172437", "GSM2172438", "GSM2172439", "GSM2172440", "GSM2172441", "GSM2172442", "GSM2172443", "GSM2172444", "GSM2172445", "GSM2172446", "GSM2172447", "GSM2172448", "GSM2172449", "GSM2172450", "GSM2172451", "GSM2172452", "GSM2172453", "GSM2172454", "GSM2172455", "GSM2172456", "GSM2172457", "GSM2172458", "GSM2172459", "GSM2172460", "GSM2172461", "GSM2172462", "GSM2172463", "GSM2172464", "GSM2172465", "GSM2172466", "GSM2172467", "GSM2172468", "GSM2172469", "GSM2172470", "GSM2172471", "GSM2172472", "GSM2172473", "GSM2172474", "GSM2172475", "GSM2172476", "GSM2172477", "GSM2172478", "GSM2172479", "GSM2172480", "GSM2172481", "GSM2172482", "GSM2172483", "GSM2172484", "GSM2172485", "GSM2172486", "GSM2172487", "GSM2172488", "GSM2172489", "GSM2172490", "GSM2172491", "GSM2172492", "GSM2172493", "GSM2172494", "GSM2172495", "GSM2172496", "GSM2172497", "GSM2172498", "GSM2172499", "GSM2172500", "GSM2172501", "GSM2172502", "GSM2172503", "GSM2172504", "GSM2172505", "GSM2172506", "GSM2172507", "GSM2172508", "GSM2172509", "GSM2172510", "GSM2172511", "GSM2172512", "GSM2172513", "GSM2172514", "GSM2172515", "GSM2172516", "GSM2172517", "GSM2172518", "GSM2172519", "GSM2172520", "GSM2172521", "GSM2172522", "GSM2172523", "GSM2172524", "GSM2172525", "GSM2172526", "GSM2172527", "GSM2172528", "GSM2172529", "GSM2172530", "GSM2172531", "GSM2172532", "GSM2172533", "GSM2172534", "GSM2172535", "GSM2172536", "GSM2172537", "GSM2172538", "GSM2172539", "GSM2172540", "GSM2172541", "GSM2172542", "GSM2172543", "GSM2172544", "GSM2172545", "GSM2172546", "GSM2172547", "GSM2172548", "GSM2172549", "GSM2172550", "GSM2172551", "GSM2172552", "GSM2172553", "GSM2172554", "GSM2172555", "GSM2172556", "GSM2172557", "GSM2172558", "GSM2172559", "GSM2172560", "GSM2172561", "GSM2172562", "GSM2172563", "GSM2172564", "GSM2172565", "GSM2172566", "GSM2172567", "GSM2172568", "GSM2172569", "GSM2172570", "GSM2172571", "GSM2172572", "GSM2172573", "GSM2172574", "GSM2172575", "GSM2172576", "GSM2172577", "GSM2172578", "GSM2172579", "GSM2172580", "GSM2172581", "GSM2172582", "GSM2172583", "GSM2172584", "GSM2172585", "GSM2172586", "GSM2172587", "GSM2172588", "GSM2172589", "GSM2172590", "GSM2172591", "GSM2172592", "GSM2172593", "GSM2172594", "GSM2172595", "GSM2172596", "GSM2172597", "GSM2172598", "GSM2172599", "GSM2172600", "GSM2172601", "GSM2172602", "GSM2172603", "GSM2172604", "GSM2172605", "GSM2172606", "GSM2172607", "GSM2172608", "GSM2172609", "GSM2172610", "GSM2172611", "GSM2172612", "GSM2172613", "GSM2172614", "GSM2172615", "GSM2172616", "GSM2172617", "GSM2172618", "GSM2172619", "GSM2172620", "GSM2172621", "GSM2172622", "GSM2172623", "GSM2172624", "GSM2172625", "GSM2172626", "GSM2172627", "GSM2172628", "GSM2172629", "GSM2172630", "GSM2172631", "GSM2172632", "GSM2172633", "GSM2172634", "GSM2172635", "GSM2172636", "GSM2172637", "GSM2172638", "GSM2172639", "GSM2172640", "GSM2172641", "GSM2172642", "GSM2172643", "GSM2172644", "GSM2172645", "GSM2172646", "GSM2172647", "GSM2172648", "GSM2172649", "GSM2172650", "GSM2172651", "GSM2172652", "GSM2172653", "GSM2172654", "GSM2172655", "GSM2172656", "GSM2172657", "GSM2172658", "GSM2172659", "GSM2172660", "GSM2172661", "GSM2172662", "GSM2172663", "GSM2172664", "GSM2172665", "GSM2172666", "GSM2172667", "GSM2172668", "GSM2172669", "GSM2172670", "GSM2172671", "GSM2172672", "GSM2172673", "GSM2172674", "GSM2172675", "GSM2172676", "GSM2172677", "GSM2172678", "GSM2172679", "GSM2172680", "GSM2172681", "GSM2172682", "GSM2172683", "GSM2172684", "GSM2172685", "GSM2172686", "GSM2172687", "GSM2172688", "GSM2172689", "GSM2172690", "GSM2172691", "GSM2172692", "GSM2172693", "GSM2172694", "GSM2172695", "GSM2172696", "GSM2172697", "GSM2172698", "GSM2172699", "GSM2172700", "GSM2172701", "GSM2172702", "GSM2172703", "GSM2172704", "GSM2172705", "GSM2172706", "GSM2172707", "GSM2172708", "GSM2172709", "GSM2172710", "GSM2172711", "GSM2172712", "GSM2172713", "GSM2172714", "GSM2172715", "GSM2172716", "GSM2172717", "GSM2172718", "GSM2172719", "GSM2172720", "GSM2172721", "GSM2172722", "GSM2172723", "GSM2172724", "GSM2172725", "GSM2172726", "GSM2172727", "GSM2172728", "GSM2172729", "GSM2172730", "GSM2172731", "GSM2172732", "GSM2172733", "GSM2172734", "GSM2172735", "GSM2172736", "GSM2172737", "GSM2172738", "GSM2172739", "GSM2172740", "GSM2172741", "GSM2172742", "GSM2172743", "GSM2172744", "GSM2172745", "GSM2172746", "GSM2172747", "GSM2172748", "GSM2172749", "GSM2172750", "GSM2172751", "GSM2172752", "GSM2172753", "GSM2172754", "GSM2172755", "GSM2172756", "GSM2172757", "GSM2172758", "GSM2172759", "GSM2172760", "GSM2172761", "GSM2172762", "GSM2172763", "GSM2172764", "GSM2172765", "GSM2172766", "GSM2172767", "GSM2172768", "GSM2172769", "GSM2172770", "GSM2172771", "GSM2172772", "GSM2172773", "GSM2172774", "GSM2172775", "GSM2172776", "GSM2172777", "GSM2172778", "GSM2172779", "GSM2172780", "GSM2172781", "GSM2172782", "GSM2172783", "GSM2172784", "GSM2172785", "GSM2172786", "GSM2172787", "GSM2172788", "GSM2172789", "GSM2172790", "GSM2172791", "GSM2172792", "GSM2172793", "GSM2172794", "GSM2172795", "GSM2172796", "GSM2172797", "GSM2172798", "GSM2172799", "GSM2172800", "GSM2172801", "GSM2172802", "GSM2172803", "GSM2172804", "GSM2172805", "GSM2172806", "GSM2172807", "GSM2172808", "GSM2172809", "GSM2172810", "GSM2172811", "GSM2172812", "GSM2172813", "GSM2172814", "GSM2172815", "GSM2172816", "GSM2172817", "GSM2172818", "GSM2172819", "GSM2172820", "GSM2172821", "GSM2172822", "GSM2172823", "GSM2172824", "GSM2172825", "GSM2172826", "GSM2172827", "GSM2172828", "GSM2172829", "GSM2172830", "GSM2172831", "GSM2172832", "GSM2172833", "GSM2172834", "GSM2172835", "GSM2172836", "GSM2172837", "GSM2172838", "GSM2172839", "GSM2172840", "GSM2172841", "GSM2172842", "GSM2172843", "GSM2172844", "GSM2172845", "GSM2172846", "GSM2172847", "GSM2172848", "GSM2172849", "GSM2172850", "GSM2172851", "GSM2172852", "GSM2172853", "GSM2172854", "GSM2172855", "GSM2172856", "GSM2172857", "GSM2172858", "GSM2172859", "GSM2172860", "GSM2172861", "GSM2172862", "GSM2172863", "GSM2172864", "GSM2172865", "GSM2172866", "GSM2172867", "GSM2172868", "GSM2172869", "GSM2172870", "GSM2172871", "GSM2172872", "GSM2172873", "GSM2172874", "GSM2172875", "GSM2172876", "GSM2172877", "GSM2172878", "GSM2172879", "GSM2172880", "GSM2172881", "GSM2172882", "GSM2172883", "GSM2172884", "GSM2172885", "GSM2172886", "GSM2172887", "GSM2172888", "GSM2172889", "GSM2172890", "GSM2172891", "GSM2172892", "GSM2172893", "GSM2172894", "GSM2172895", "GSM2172896", "GSM2172897", "GSM2172898", "GSM2172899", "GSM2172900", "GSM2172901", "GSM2172902", "GSM2172903", "GSM2172904", "GSM2172905", "GSM2172906", "GSM2172907", "GSM2172908", "GSM2172909", "GSM2172910", "GSM2172911", "GSM2172912", "GSM2172913", "GSM2172914", "GSM2172915", "GSM2172916", "GSM2172917", "GSM2172918", "GSM2172919", "GSM2172920", "GSM2172921", "GSM2172922", "GSM2172923", "GSM2172924", "GSM2172925", "GSM2172926", "GSM2172927", "GSM2172928", "GSM2172929", "GSM2172930", "GSM2172931", "GSM2172932", "GSM2172933", "GSM2172934", "GSM2172935", "GSM2172936", "GSM2172937", "GSM2172938", "GSM2172939", "GSM2172940", "GSM2172941", "GSM2172942", "GSM2172943", "GSM2172944", "GSM2172945", "GSM2172946", "GSM2172947", "GSM2172948", "GSM2172949", "GSM2172950", "GSM2172951", "GSM2172952", "GSM2172953", "GSM2172954", "GSM2172955", "GSM2172956", "GSM2172957", "GSM2172958", "GSM2172959", "GSM2172960", "GSM2172961", "GSM2172962", "GSM2172963", "GSM2172964", "GSM2172965", "GSM2172966", "GSM2172967", "GSM2172968", "GSM2172969", "GSM2172970", "GSM2172971", "GSM2172972", "GSM2172973", "GSM2172974", "GSM2172975", "GSM2172976", "GSM2172977", "GSM2172978", "GSM2172979", "GSM2172980", "GSM2172981", "GSM2172982", "GSM2172983", "GSM2172984", "GSM2172985", "GSM2172986", "GSM2172987", "GSM2172988", "GSM2172989", "GSM2172990", "GSM2172991", "GSM2172992", "GSM2172993", "GSM2172994", "GSM2172995", "GSM2172996", "GSM2172997", "GSM2172998", "GSM2172999", "GSM2173000", "GSM2173001", "GSM2173002", "GSM2173003", "GSM2173004", "GSM2173005", "GSM2173006", "GSM2173007", "GSM2173008", "GSM2173009", "GSM2173010", "GSM2173011", "GSM2173012", "GSM2173013", "GSM2173014", "GSM2173015", "GSM2173016", "GSM2173017", "GSM2173018", "GSM2173019", "GSM2173020", "GSM2173021", "GSM2173022", "GSM2173023", "GSM2173024", "GSM2173025", "GSM2173026", "GSM2173027", "GSM2173028", "GSM2173029", "GSM2173030", "GSM2173031", "GSM2173032", "GSM2173033", "GSM2173034", "GSM2173035", "GSM2173036", "GSM2173037", "GSM2173038", "GSM2173039", "GSM2173040", "GSM2173041", "GSM2173042", "GSM2173043", "GSM2173044", "GSM2173045", "GSM2173046", "GSM2173047", "GSM2173048", "GSM2173049", "GSM2173050", "GSM2173051", "GSM2173052", "GSM2173053", "GSM2173054", "GSM2173055", "GSM2173056", "GSM2173057", "GSM2173058", "GSM2173059", "GSM2173060", "GSM2173061", "GSM2173062", "GSM2173063", "GSM2173064", "GSM2173065", "GSM2173066", "GSM2173067", "GSM2173068", "GSM2173069", "GSM2173070", "GSM2173071", "GSM2173072", "GSM2173073", "GSM2173074", "GSM2173075", "GSM2173076", "GSM2173077", "GSM2173078", "GSM2173079", "GSM2173080", "GSM2173081", "GSM2173082", "GSM2173083", "GSM2173084", "GSM2173085", "GSM2173086", "GSM2173087", "GSM2173088", "GSM2173089", "GSM2173090", "GSM2173091", "GSM2173092", "GSM2173093", "GSM2173094", "GSM2173095", "GSM2173096", "GSM2173097", "GSM2173098", "GSM2173099", "GSM2173100", "GSM2173101", "GSM2173102", "GSM2173103", "GSM2173104", "GSM2173105", "GSM2173106", "GSM2173107", "GSM2173108", "GSM2173109", "GSM2173110", "GSM2173111", "GSM2173112", "GSM2173113", "GSM2173114", "GSM2173115", "GSM2173116", "GSM2173117", "GSM2173118", "GSM2173119", "GSM2173120", "GSM2173121", "GSM2173122", "GSM2173123", "GSM2173124", "GSM2173125", "GSM2173126", "GSM2173127", "GSM2173128", "GSM2173129", "GSM2173130", "GSM2173131", "GSM2173132", "GSM2173133", "GSM2173134", "GSM2173135", "GSM2173136", "GSM2173137", "GSM2173138", "GSM2173139", "GSM2173140", "GSM2173141", "GSM2173142", "GSM2173143", "GSM2173144", "GSM2173145", "GSM2173146", "GSM2173147", "GSM2173148", "GSM2173149", "GSM2173150", "GSM2173151", "GSM2173152", "GSM2173153", "GSM2173154", "GSM2173155", "GSM2173156", "GSM2173157", "GSM2173158", "GSM2173159", "GSM2173160", "GSM2173161", "GSM2173162", "GSM2173163", "GSM2173164", "GSM2173165", "GSM2173166", "GSM2173167", "GSM2173168", "GSM2173169", "GSM2173170", "GSM2173171", "GSM2173172", "GSM2173173", "GSM2173174", "GSM2173175", "GSM2173176", "GSM2173177", "GSM2173178", "GSM2173179", "GSM2173180", "GSM2173181", "GSM2173182", "GSM2173183", "GSM2173184", "GSM2173185", "GSM2173186", "GSM2173187", "GSM2173188", "GSM2173189", "GSM2173190", "GSM2173191", "GSM2173192", "GSM2173193", "GSM2173194", "GSM2173195", "GSM2173196", "GSM2173197", "GSM2173198", "GSM2173199", "GSM2173200", "GSM2173201", "GSM2173202", "GSM2173203", "GSM2173204", "GSM2173205", "GSM2173206", "GSM2173207", "GSM2173208", "GSM2173209", "GSM2173210", "GSM2173211", "GSM2173212", "GSM2173213", "GSM2173214", "GSM2173215", "GSM2173216", "GSM2173217", "GSM2173218", "GSM2173219", "GSM2173220", "GSM2173221", "GSM2173222", "GSM2173223", "GSM2173224", "GSM2173225", "GSM2173226", "GSM2173227", "GSM2173228", "GSM2173229", "GSM2173230", "GSM2173231", "GSM2173232", "GSM2173233", "GSM2173234", "GSM2173235", "GSM2173236", "GSM2173237", "GSM2173238", "GSM2173239", "GSM2173240", "GSM2173241", "GSM2173242", "GSM2173243", "GSM2173244", "GSM2173245", "GSM2173246", "GSM2173247", "GSM2173248", "GSM2173249", "GSM2173250", "GSM2173251", "GSM2173252", "GSM2173253", "GSM2173254", "GSM2173255", "GSM2173256", "GSM2173257", "GSM2173258", "GSM2173259", "GSM2173260", "GSM2173261", "GSM2173262", "GSM2173263", "GSM2173264", "GSM2173265", "GSM2173266", "GSM2173267", "GSM2173268", "GSM2173269", "GSM2173270", "GSM2173271", "GSM2173272", "GSM2173273", "GSM2173274", "GSM2173275", "GSM2173276", "GSM2173277", "GSM2173278", "GSM2173279", "GSM2173280", "GSM2173281", "GSM2173282", "GSM2173283", "GSM2173284", "GSM2173285", "GSM2173286", "GSM2173287", "GSM2173288", "GSM2173289", "GSM2173290", "GSM2173291", "GSM2173292", "GSM2173293", "GSM2173294", "GSM2173295", "GSM2173296", "GSM2173297", "GSM2173298", "GSM2173299", "GSM2173300", "GSM2173301", "GSM2173302", "GSM2173303", "GSM2173304", "GSM2173305", "GSM2173306", "GSM2173307", "GSM2173308", "GSM2173309", "GSM2173310", "GSM2173311", "GSM2173312", "GSM2173313", "GSM2173314", "GSM2173315", "GSM2173316", "GSM2173317", "GSM2173318", "GSM2173319", "GSM2173320", "GSM2173321", "GSM2173322", "GSM2173323", "GSM2173324", "GSM2173325", "GSM2173326", "GSM2173327", "GSM2173328", "GSM2173329", "GSM2173330", "GSM2173331", "GSM2173332", "GSM2173333", "GSM2173334", "GSM2173335", "GSM2173336", "GSM2173337", "GSM2173338", "GSM2173339", "GSM2173340", "GSM2173341", "GSM2173342", "GSM2173343", "GSM2173344", "GSM2173345", "GSM2173346", "GSM2173347", "GSM2173348", "GSM2173349", "GSM2173350", "GSM2173351", "GSM2173352", "GSM2173353", "GSM2173354", "GSM2173355", "GSM2173356", "GSM2173357", "GSM2173358", "GSM2173359", "GSM2173360", "GSM2173361", "GSM2173362", "GSM2173363", "GSM2173364", "GSM2173365", "GSM2173366", "GSM2173367", "GSM2173368", "GSM2173369", "GSM2173370", "GSM2173371", "GSM2173372", "GSM2173373", "GSM2173374", "GSM2173375", "GSM2173376", "GSM2173377", "GSM2173378", "GSM2173379", "GSM2173380", "GSM2173381", "GSM2173382", "GSM2173383", "GSM2173384", "GSM2173385", "GSM2173386", "GSM2173387", "GSM2173388", "GSM2173389", "GSM2173390", "GSM2173391", "GSM2173392", "GSM2173393", "GSM2173394", "GSM2173395", "GSM2173396", "GSM2173397", "GSM2173398", "GSM2173399", "GSM2173400", "GSM2173401", "GSM2173402", "GSM2173403", "GSM2173404", "GSM2173405", "GSM2173406", "GSM2173407", "GSM2173408", "GSM2173409", "GSM2173410", "GSM2173411", "GSM2173412", "GSM2173413", "GSM2173414", "GSM2173415", "GSM2173416", "GSM2173417", "GSM2173418", "GSM2173419", "GSM2173420", "GSM2173421", "GSM2173422", "GSM2173423", "GSM2173424", "GSM2173425", "GSM2173426", "GSM2173427", "GSM2173428", "GSM2173429", "GSM2173430", "GSM2173431", "GSM2173432", "GSM2173433", "GSM2173434", "GSM2173435", "GSM2173436", "GSM2173437", "GSM2173438", "GSM2173439", "GSM2173440", "GSM2173441", "GSM2173442", "GSM2173443", "GSM2173444", "GSM2173445", "GSM2173446", "GSM2173447", "GSM2173448", "GSM2173449", "GSM2173450", "GSM2173451", "GSM2173452", "GSM2173453", "GSM2173454", "GSM2173455", "GSM2173456", "GSM2173457", "GSM2173458", "GSM2173459", "GSM2173460", "GSM2173461", "GSM2173462", "GSM2173463", "GSM2173464", "GSM2173465", "GSM2173466", "GSM2173467", "GSM2173468", "GSM2173469", "GSM2173470", "GSM2173471", "GSM2173472", "GSM2173473", "GSM2173474", "GSM2173475", "GSM2173476", "GSM2173477", "GSM2173478", "GSM2173479", "GSM2173480", "GSM2173481", "GSM2173482", "GSM2173483", "GSM2173484", "GSM2173485", "GSM2173486", "GSM2173487", "GSM2173488", "GSM2173489", "GSM2173490", "GSM2173491", "GSM2173492", "GSM2173493", "GSM2173494", "GSM2173495", "GSM2173496", "GSM2173497", "GSM2173498", "GSM2173499", "GSM2173500", "GSM2173501", "GSM2173502", "GSM2173503", "GSM2173504", "GSM2173505", "GSM2173506", "GSM2173507", "GSM2173508", "GSM2173509", "GSM2173510", "GSM2173511", "GSM2173513", "GSM2173515", "GSM2173516", "GSM2173517", "GSM2173518", "GSM2173519", "GSM2173520", "GSM2173521", "GSM2173522", "GSM2173523", "GSM2173524", "GSM2173525", "GSM2173526", "GSM2173527", "GSM2173528", "GSM2173529", "GSM2173530", "GSM2173531", "GSM2173532", "GSM2173533", "GSM2173534", "GSM2173535", "GSM2173536", "GSM2173537", "GSM2173538", "GSM2173539", "GSM2173540", "GSM2173541", "GSM2173542", "GSM2173543", "GSM2173544", "GSM2173545", "GSM2173546", "GSM2173547", "GSM2173548", "GSM2173549", "GSM2173550", "GSM2173551", "GSM2173552", "GSM2173553", "GSM2173554", "GSM2173555", "GSM2173556", "GSM2173557", "GSM2173558", "GSM2173559", "GSM2173560", "GSM2173561", "GSM2173562", "GSM2173563", "GSM2173564", "GSM2173565", "GSM2173566", "GSM2173567", "GSM2173568", "GSM2173569", "GSM2173570", "GSM2173571", "GSM2173572", "GSM2173573", "GSM2173574", "GSM2173575", "GSM2173576", "GSM2173577", "GSM2173578", "GSM2173579", "GSM2173580", "GSM2173581", "GSM2173582", "GSM2173583", "GSM2173584", "GSM2173585", "GSM2173586", "GSM2173587", "GSM2173588", "GSM2173589", "GSM2173590", "GSM2173591", "GSM2173592", "GSM2173593", "GSM2173594", "GSM2173595", "GSM2173596", "GSM2173597", "GSM2173598", "GSM2173599", "GSM2173600", "GSM2173601", "GSM2173602", "GSM2173603", "GSM2173604", "GSM2173605", "GSM2173606", "GSM2173607", "GSM2173608", "GSM2173609", "GSM2173610", "GSM2173611", "GSM2173612", "GSM2173613", "GSM2173614", "GSM2173615", "GSM2173616", "GSM2173617", "GSM2173618", "GSM2173619", "GSM2173620", "GSM2173621", "GSM2173622", "GSM2173623", "GSM2173624", "GSM2173625", "GSM2173626", "GSM2173627", "GSM2173628", "GSM2173629", "GSM2173630", "GSM2173631", "GSM2173632", "GSM2173633", "GSM2173634", "GSM2173635", "GSM2173636", "GSM2173637", "GSM2173638", "GSM2173639", "GSM2173640", "GSM2173641", "GSM2173642", "GSM2173643", "GSM2173644", "GSM2173645", "GSM2173646", "GSM2173647", "GSM2173648", "GSM2173649", "GSM2173650", "GSM2173651", "GSM2173652", "GSM2173653", "GSM2173654", "GSM2173655", "GSM2173656", "GSM2173657", "GSM2173658", "GSM2173659", "GSM2173660", "GSM2173661", "GSM2173662", "GSM2173663", "GSM2173664", "GSM2173665", "GSM2173666", "GSM2173667", "GSM2173668", "GSM2173669", "GSM2173670", "GSM2173671", "GSM2173672", "GSM2173673", "GSM2173674", "GSM2173675", "GSM2173676", "GSM2173677", "GSM2173678", "GSM2173679", "GSM2173680", "GSM2173681", "GSM2173682", "GSM2173683", "GSM2173684", "GSM2173685", "GSM2173686", "GSM2173687", "GSM2173688", "GSM2173689", "GSM2173690", "GSM2173691", "GSM2173692", "GSM2173693", "GSM2173694", "GSM2173695", "GSM2173696", "GSM2173697", "GSM2173698", "GSM2173699", "GSM2173700", "GSM2173701", "GSM2173702", "GSM2173703", "GSM2173704", "GSM2173705", "GSM2173706", "GSM2173707", "GSM2173708", "GSM2173709", "GSM2173710", "GSM2173711", "GSM2173712", "GSM2173713", "GSM2173714", "GSM2173715", "GSM2173716", "GSM2173717", "GSM2173718", "GSM2173719", "GSM2173720", "GSM2173721", "GSM2173722", "GSM2173723", "GSM2173724", "GSM2173725", "GSM2173726", "GSM2173727", "GSM2173728", "GSM2173729", "GSM2173730", "GSM2173731", "GSM2173732", "GSM2173733", "GSM2173734", "GSM2173735", "GSM2173736", "GSM2173737", "GSM2173738", "GSM2173739", "GSM2173740", "GSM2173741", "GSM2173742", "GSM2173743", "GSM2173744", "GSM2173745", "GSM2173746", "GSM2173747", "GSM2173748", "GSM2173749", "GSM2173750", "GSM2173751", "GSM2173752", "GSM2173753", "GSM2173754", "GSM2173755", "GSM2173756", "GSM2173757", "GSM2173758", "GSM2173759", "GSM2173760", "GSM2173761", "GSM2173762", "GSM2173763", "GSM2173764", "GSM2173765", "GSM2173766", "GSM2173767", "GSM2173768", "GSM2173769", "GSM2173770", "GSM2173771", "GSM2173772", "GSM2173773", "GSM2173774", "GSM2173775", "GSM2173776", "GSM2173777", "GSM2173778", "GSM2173779", "GSM2173780", "GSM2173781", "GSM2173782", "GSM2173783", "GSM2173784", "GSM2173785", "GSM2173786", "GSM2173787", "GSM2173788", "GSM2173789", "GSM2173790", "GSM2173791", "GSM2173792", "GSM2173793", "GSM2173794", "GSM2173795", "GSM2173796", "GSM2173797", "GSM2173798", "GSM2173799", "GSM2173800", "GSM2173801", "GSM2173802", "GSM2173803", "GSM2173804", "GSM2173805", "GSM2173806", "GSM2173807", "GSM2173808", "GSM2173809", "GSM2173810", "GSM2173811", "GSM2173812", "GSM2173813", "GSM2173814", "GSM2173815", "GSM2173816", "GSM2173817", "GSM2173818", "GSM2173819", "GSM2173820", "GSM2173821", "GSM2173822", "GSM2173823", "GSM2173824", "GSM2173825", "GSM2173826", "GSM2173827", "GSM2173828", "GSM2173829", "GSM2173830", "GSM2173831", "GSM2173832", "GSM2173833", "GSM2173834", "GSM2173835", "GSM2173836", "GSM2173837", "GSM2173838", "GSM2173839", "GSM2173840", "GSM2173841", "GSM2173842", "GSM2173843", "GSM2173844", "GSM2173845", "GSM2173846", "GSM2173847", "GSM2173848", "GSM2173849", "GSM2173850", "GSM2173851", "GSM2173852", "GSM2173853", "GSM2173854", "GSM2173855", "GSM2173856", "GSM2173857", "GSM2173858", "GSM2173859", "GSM2173860", "GSM2173861", "GSM2173862", "GSM2173863", "GSM2173864", "GSM2173865", "GSM2173866", "GSM2173867", "GSM2173868", "GSM2173869", "GSM2173870", "GSM2173871", "GSM2173872", "GSM2173873", "GSM2173874", "GSM2173875", "GSM2173876", "GSM2173877", "GSM2173878", "GSM2173879", "GSM2173880", "GSM2173881", "GSM2173882", "GSM2173883", "GSM2173884", "GSM2173885", "GSM2173886", "GSM2173887", "GSM2173888", "GSM2173889", "GSM2173890", "GSM2173891", "GSM2173892", "GSM2173893", "GSM2173894", "GSM2173895", "GSM2173896", "GSM2173897", "GSM2173898", "GSM2173899", "GSM2173900", "GSM2173901", "GSM2173902", "GSM2173903", "GSM2173904", "GSM2173905", "GSM2173906", "GSM2173907", "GSM2173908", "GSM2173909", "GSM2173910", "GSM2173911", "GSM2173912", "GSM2173913", "GSM2173914", "GSM2173915", "GSM2173916", "GSM2173917", "GSM2173918", "GSM2173919", "GSM2173920", "GSM2173921", "GSM2173922", "GSM2173923", "GSM2173924", "GSM2173925", "GSM2173926", "GSM2173927", "GSM2173928", "GSM2173929", "GSM2173930", "GSM2173931", "GSM2173932", "GSM2173933", "GSM2173934", "GSM2173935", "GSM2173936", "GSM2173937", "GSM2173938", "GSM2173939", "GSM2173940", "GSM2173941", "GSM2173942", "GSM2173943", "GSM2173944", "GSM2173945", "GSM2173946", "GSM2173947", "GSM2173948", "GSM2173949", "GSM2173950", "GSM2173951", "GSM2173952", "GSM2173953", "GSM2173954", "GSM2173955", "GSM2173956", "GSM2173957", "GSM2173958", "GSM2173959", "GSM2173960", "GSM2173961", "GSM2173962", "GSM2173963", "GSM2173964", "GSM2173965", "GSM2173966", "GSM2173967", "GSM2173968", "GSM2173969", "GSM2173970", "GSM2173971", "GSM2173972", "GSM2173973", "GSM2173974", "GSM2173975", "GSM2173976", "GSM2173977", "GSM2173978", "GSM2173979", "GSM2173980", "GSM2173981", "GSM2173982", "GSM2173983", "GSM2173984", "GSM2173985", "GSM2173986", "GSM2173987", "GSM2173988", "GSM2173989", "GSM2173990", "GSM2173991", "GSM2173992", "GSM2173993", "GSM2173994", "GSM2173995", "GSM2173996", "GSM2173997", "GSM2173998", "GSM2173999", "GSM2174000", "GSM2174001", "GSM2174002", "GSM2174003", "GSM2174004", "GSM2174005", "GSM2174006", "GSM2174007", "GSM2174008", "GSM2174009", "GSM2174010", "GSM2174011", "GSM2174012", "GSM2174013", "GSM2174014", "GSM2174015", "GSM2174016", "GSM2174017", "GSM2174018", "GSM2174019", "GSM2174020", "GSM2174021", "GSM2174022", "GSM2174023", "GSM2174024", "GSM2174025", "GSM2174026", "GSM2174027", "GSM2174028", "GSM2174029", "GSM2174030", "GSM2174031", "GSM2174032", "GSM2174033", "GSM2174034", "GSM2174035", "GSM2174036", "GSM2174037", "GSM2174038", "GSM2174039", "GSM2174040", "GSM2174041", "GSM2174042", "GSM2174043", "GSM2174044", "GSM2174045", "GSM2174046", "GSM2174047", "GSM2174048", "GSM2174049", "GSM2174050", "GSM2174051", "GSM2174052", "GSM2174053", "GSM2174054", "GSM2174055", "GSM2174056", "GSM2174057", "GSM2174058", "GSM2174059", "GSM2174060", "GSM2174061", "GSM2174062", "GSM2174063", "GSM2174064", "GSM2174065", "GSM2174066", "GSM2174067", "GSM2174068", "GSM2174069", "GSM2174070", "GSM2174071", "GSM2174072", "GSM2174073", "GSM2174074", "GSM2174075", "GSM2174076", "GSM2174077", "GSM2174078", "GSM2174079", "GSM2174080", "GSM2174081", "GSM2174082", "GSM2174083", "GSM2174084", "GSM2174085", "GSM2174086", "GSM2174087", "GSM2174088", "GSM2174089", "GSM2174090", "GSM2174091", "GSM2174092", "GSM2174093", "GSM2174094", "GSM2174095", "GSM2174096", "GSM2174097", "GSM2174098", "GSM2174099", "GSM2174100", "GSM2174101", "GSM2174102", "GSM2174103", "GSM2174104", "GSM2174105", "GSM2174106", "GSM2174107", "GSM2174108", "GSM2174109", "GSM2174110", "GSM2174111", "GSM2174112", "GSM2174113", "GSM2174114", "GSM2174115", "GSM2174116", "GSM2174117", "GSM2174118", "GSM2174119", "GSM2174120", "GSM2174121", "GSM2174122", "GSM2174123", "GSM2174124", "GSM2174125", "GSM2174126", "GSM2174127", "GSM2174128", "GSM2174129", "GSM2174130", "GSM2174131", "GSM2174132", "GSM2174133", "GSM2174134", "GSM2174135", "GSM2174136", "GSM2174137", "GSM2174138", "GSM2174139", "GSM2174140", "GSM2174141", "GSM2174142", "GSM2174143", "GSM2174144", "GSM2174145", "GSM2174146", "GSM2174147", "GSM2174148", "GSM2174149", "GSM2174150", "GSM2174151", "GSM2174152", "GSM2174153", "GSM2174154", "GSM2174155", "GSM2174156", "GSM2174157", "GSM2174158", "GSM2174159", "GSM2174160", "GSM2174161", "GSM2174162", "GSM2174163", "GSM2174164", "GSM2174165", "GSM2174166", "GSM2174167", "GSM2174168", "GSM2174169", "GSM2174170", "GSM2174171", "GSM2174172", "GSM2174173", "GSM2174174", "GSM2174175", "GSM2174176", "GSM2174177", "GSM2174178", "GSM2174179", "GSM2174180", "GSM2174181", "GSM2174182", "GSM2174183", "GSM2174184", "GSM2174185", "GSM2174186", "GSM2174187", "GSM2174188", "GSM2174189", "GSM2174190", "GSM2174191", "GSM2174192", "GSM2174193", "GSM2174194", "GSM2174195", "GSM2174196", "GSM2174197", "GSM2174198", "GSM2174199", "GSM2174200", "GSM2174201", "GSM2174202", "GSM2174203", "GSM2174204", "GSM2174205", "GSM2174206", "GSM2174207", "GSM2174208", "GSM2174209", "GSM2174210", "GSM2174211", "GSM2174212", "GSM2174213", "GSM2174214", "GSM2174215", "GSM2174216", "GSM2174217", "GSM2174218", "GSM2174219", "GSM2174220", "GSM2174221", "GSM2174222", "GSM2174223", "GSM2174224", "GSM2174225", "GSM2174226", "GSM2174227", "GSM2174228", "GSM2174229", "GSM2174230", "GSM2174231", "GSM2174232", "GSM2174233", "GSM2174234", "GSM2174235", "GSM2174236", "GSM2174237", "GSM2174238", "GSM2174239", "GSM2174240", "GSM2174241", "GSM2174242", "GSM2174243", "GSM2174244", "GSM2174245", "GSM2174246", "GSM2174247", "GSM2174248", "GSM2174249", "GSM2174250", "GSM2174251", "GSM2174252", "GSM2174253", "GSM2174254", "GSM2174255", "GSM2174256", "GSM2174257", "GSM2174258", "GSM2174259", "GSM2174260", "GSM2174261", "GSM2174262", "GSM2174263", "GSM2174264", "GSM2174265", "GSM2174266", "GSM2174267", "GSM2174268", "GSM2174269", "GSM2174270", "GSM2174271", "GSM2174272", "GSM2174273", "GSM2174274", "GSM2174275", "GSM2174276", "GSM2174277", "GSM2174278", "GSM2174279", "GSM2174280", "GSM2174281", "GSM2174282", "GSM2174283", "GSM2174284", "GSM2174285", "GSM2174286", "GSM2174287", "GSM2174288", "GSM2174289", "GSM2174290", "GSM2174291", "GSM2174292", "GSM2174293", "GSM2174294", "GSM2174295", "GSM2174296", "GSM2174297", "GSM2174298", "GSM2174299", "GSM2174300", "GSM2174301", "GSM2174302", "GSM2174303", "GSM2174304", "GSM2174305", "GSM2174306", "GSM2174307", "GSM2174308", "GSM2174309", "GSM2174310", "GSM2174311", "GSM2174312", "GSM2174313", "GSM2174314", "GSM2174315", "GSM2174316", "GSM2174317", "GSM2174318", "GSM2174319", "GSM2174320", "GSM2174321", "GSM2174322", "GSM2174323", "GSM2174324", "GSM2174325", "GSM2174326", "GSM2174327", "GSM2174328", "GSM2174329", "GSM2174330", "GSM2174331", "GSM2174332", "GSM2174333", "GSM2174334", "GSM2174335", "GSM2174336", "GSM2174337", "GSM2174338", "GSM2174339", "GSM2174340", "GSM2174341", "GSM2174342", "GSM2174343", "GSM2174344", "GSM2174345", "GSM2174346", "GSM2174347", "GSM2174348", "GSM2174349", "GSM2174350", "GSM2174351", "GSM2174352", "GSM2174353", "GSM2174354", "GSM2174355", "GSM2174356", "GSM2174357", "GSM2174358", "GSM2174359", "GSM2174360", 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"18573", "taxon": "Homo sapiens", "title": "Single cell transcriptome analysis of human pancreas reveals transcriptional signatures of aging and somatic mutation patterns.", "resolution_checked_at": "2026-11-01T19:09:46Z", "resolution_check": "identifier_resolution_only_no_download_no_licence_read", "downloaded": false, "licence_read": false}}, {"id": "data:geo:GSE81608", "role": "raw", "format": "geo-series", "media_type": "application/vnd.ncbi.geo-series+json", "uri": "https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE81608", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE81608", "version": null, "note": "scRNAseq data generated by our laboratory and used in this study are available in the Gene Expression Omnibus (GEO; www.ncbi.nlm.nih.gov/geo/), accession number GSE218316.", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "scRNAseq 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"2026-11-01T18:46:34Z", "resolution_check": "identifier_resolution_only_no_download_no_licence_read", "downloaded": false, "licence_read": false}}, {"id": "data:geo:GSE83139", "role": "raw", "format": "geo-series", "media_type": "application/vnd.ncbi.geo-series+json", "uri": "https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE83139", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE83139", "version": null, "note": "scRNAseq data generated by our laboratory and used in this study are available in the Gene Expression Omnibus (GEO; www.ncbi.nlm.nih.gov/geo/), accession number GSE218316.", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "scRNAseq data generated by our laboratory and used in this study are available in the Gene Expression Omnibus (GEO; www.ncbi.nlm.nih.gov/geo/), accession number GSE218316.", "access_statement_kind": 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"sample_count": 635, "group_sizes": null, "group_sizes_basis": null, "platform": "11154;16791", "taxon": "Homo sapiens", "title": "Single cell RNA-seq of human pancreatic endocrine cells from Juvenile, adult control and type 2 diabetic donors.", "resolution_checked_at": "2026-11-01T19:09:46Z", "resolution_check": "identifier_resolution_only_no_download_no_licence_read", "downloaded": false, "licence_read": false}}], "gaps": ["asset:data:geo:E-MTAB-5061 not downloaded", "asset:data:geo:E-MTAB-5061 licence not read", "asset:data:geo:GSE218316 not downloaded", "asset:data:geo:GSE218316 licence not read", "asset:data:geo:GSE81547 not downloaded", "asset:data:geo:GSE81547 licence not read", "asset:data:geo:GSE81608 not downloaded", "asset:data:geo:GSE81608 licence not read", "asset:data:geo:GSE83139 not downloaded", "asset:data:geo:GSE83139 licence not read"]}, "analysis": {"state": "partial", "methods": [{"id": "method-1", "family": "group_comparison", "specific": "wilcoxon", "label": 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METHODS: We used single-cell transcriptomics datasets of primary human pancreatic islet c", "development of diabetes. DATA AVAILABILITY: scRNAseq data generated by our laboratory and used in", "n Bioinformatics Institute E-MTAB-5061 [36]) scRNA-seq datasets of human pancreatic islets were sel"], "order_basis": "paper_text_order:453", "id": "assay:2"}, {"role": "data_generation", "definition_id": "rna_seq", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.83, "evidence": ["ta cell damage. METHODS: We used single-cell transcriptomics datasets of primary human pancreatic islet c", "Methods Transcriptomic analysis of type 2 diabetes datasets Four pr"], "order_basis": "paper_text_order:465", "id": "assay:3"}, {"role": "data_generation", "definition_id": "transfection", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.85, "evidence": ["ses endoplasmic reticulum stress while APOL1 knockdown prevents cytokine-induced beta cell death an"], "order_basis": "paper_text_order:1091", "id": "assay:4"}, {"role": "analysis", "definition_id": "group_comparison", "definition_version": "f2132e96ae6c7a4e", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"dsl_catalogue": "f2132e96ae6c7a4e"}, "confidence": 1.0, "evidence": ["We used our single-cell RNA-sequencing Gene Expression Omnibus (GEO; www.ncbi.nlm.nih.gov/geo/) dataset generated from human pancreatic islets treated with beta cell stressors (GSE218316) and performed a differential gene expression analysis of human islet cells treated with IL-1β + IFNγ using a Wilcoxon rank-sum test."], "order_basis": "consumes_earlier_output", "id": "assay:5"}]}