Single cell transcriptome data analysis of human and mice beta cells from diabetic and non-diabetic donors.Lavrenčič, Eva (Avtor) Jakše, Jernej (Mentor) Theis, Fabian (Komentor) beta-cell heterogeneitydiabeteshumansmicepancreatic isletsscRNA-seq data analysisspecies comparisonPancreatic β-cells, which are a highly plastic, heterogeneous group of cells, produce insulin and have a key role in glucose homeostasis. Because malfunctioning of β-cells causes diabetes, they represent a potential target for diabetes regenerative therapies. Since most diabetes studies are done on animal models that are not directly comparable to humans, the translation of the findings from animal models to humans is needed. Here, we integrated, annotated and jointly analysed five human pancreatic islet scRNA-seq datasets, focusing on the variability of more than 50.000 β-cells in health and dysfunction. We compared the human atlas to a similar previously developed resource of murine data. We found that batch effects were less effectively removed in human data than in mice, possibly due to additional, unexplained heterogeneity in humans. Differential expression analysis of β-cells from middle-aged type 2 diabetic and healthy samples identified 24 human and 2049 mice differentially expressed genes (DEGs), of which four (ALDOB, CPNE4, ITIH5, LAMB1) were differentially expressed in the same direction in both organisms. We found that disease states could explain a relatively higher proportion of variability in mice than in humans, which could explain the difference in the number of identified DEGs. Lastly, we defined ten human β-cell gene programmes (GPs) as groups of spatially covariable genes, some of which were shared with previously defined mice gene programmes. Our discoveries also corresponded to previous observations on human data, for example, the data showed heterogeneous activity of β-cell insulin production and subsequent regeneration-associated GPs. We evaluated how likely each of the gene programs resulted from true biological variability or batch effects.20242024-06-01 07:16:19Magistrsko delo/naloga158270VisID: 236591COBISS_ID: 198113795sl