{"Id":"af16f9a5-fb42-4977-ad91-bc973bda18d3","CanonicalId":"GSE101207","Url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE101207","Name":"High-throughput single cell transcriptome analysis and CRISPR screen identify key β cell-specific disease genes","Description":"Pancreatic endocrine cells orchestrate the precise control of blood glucose levels, but the contribution of each cell type to diabetes or obesity remains elusive. Here we used a massively parallel single-cell RNA-seq technology (Drop-Seq) to analyze the transcriptome of 26,677 pancreatic islets cells from both healthy and type II diabetic (T2D) donors. We have analyzed cell type-specific gene signatures, and detected several rare α or β cell subpopulations with high sensitivity. We also developed RePACT, a sensitive single cell analysis algorithm to identify genes associated with rare disease causing cells, or to capture the subtle disease-relevant cellular variation. We successfully identified both common and specific signature genes of obesity and T2D with only a small number of islet samples. We also performed an unbiased genome-wide CRISPR screen and mapped these Drop-Seq signature genes to the core insulin regulatory network in β cells. Notably, our integrative analysis discovered a β cell-specific function of the cohesin loading complex in regulating insulin gene transcription, and a previously unrecognized role of the NuA4/Tip60 histone acetyltransferase complex in regulating insulin release. These data demonstrated that single-cell trancriptomics is necessary to dissect the heterogeneity, disease state, and functionality of islet β cells and other cell types.","ResourceType":"Dataset","ParentResourceType":null,"DefiningManuscriptId":"PMID35440614","Publications":[],"Contributors":[{"Role":{"CanonicalId":"hirn-cv-ResourceRole-contact","Url":null,"Name":"Contact","OntologyId":null},"HirnUserId":"jkaddis@hirnetwork.org","FirstName":"John","LastName":"Kaddis","EmailAddress":"jkaddis@coh.org","Organization":"City of Hope","Consortia":[]},{"Role":{"CanonicalId":"hirn-cv-ResourceRole-contact","Url":null,"Name":"Contact","OntologyId":null},"HirnUserId":"daniel@hirnetwork.org","FirstName":"Daniel","LastName":"Oropeza","EmailAddress":"Daniel.Oropeza@unige.ch","Organization":"University of Geneva","Consortia":["CTAR"]}],"Vendor":{"id":null,"Name":"","Url":""},"VendorResourceName":"","VendorResourceUrl":"","VendorCatNumber":"","VendorLotNumber":"","DateCreated":"2022-04-29T21:10:12.9919362+00:00","DateModified":"2022-07-01T03:37:21.3873934+00:00","VersionId":"2","ModelVersion":"4.0","DatasetData":{"DatasetType":{"CanonicalId":"http://purl.bioontology.org/ontology/NCIT?conceptid=http%3A%2F%2Fncicb.nci.nih.gov%2Fxml%2Fowl%2FEVS%2FThesaurus.owl%23C153189","Url":"http://purl.bioontology.org/ontology/NCIT?conceptid=http%3A%2F%2Fncicb.nci.nih.gov%2Fxml%2Fowl%2FEVS%2FThesaurus.owl%23C153189","Name":"Transcriptomics Dataset","OntologyId":"NCIT"},"ExperimentDesign":{"CanonicalId":"","Url":"","Name":"","OntologyId":""},"BiosampleCharacteristics":[],"BiosampleType":[],"TechnologyType":{"CanonicalId":"","Url":"","Name":"","OntologyId":""}}}