@article{bosi_integration_2020, title = {Integration of single-cell datasets reveals novel transcriptomic signatures of β-cells in human type 2 diabetes}, volume = {2}, issn = {2631-9268}, url = {https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7679065/}, doi = {10.1093/nargab/lqaa097}, abstract = {Pancreatic islet β-cell failure is key to the onset and progression of type 2 diabetes (T2D). The advent of single-cell {RNA} sequencing ({scRNA}-seq) has opened the possibility to determine transcriptional signatures specifically relevant for T2D at the β-cell level. Yet, applications of this technique have been underwhelming, as three independent studies failed to show shared differentially expressed genes in T2D β-cells. We performed an integrative analysis of the available datasets from these studies to overcome confounding sources of variability and better highlight common T2D β-cell transcriptomic signatures. After removing low-quality transcriptomes, we retained 3046 single cells expressing 27 931 genes. Cells were integrated to attenuate dataset-specific biases, and clustered into cell type groups. In T2D β-cells (n = 801), we found 210 upregulated and 16 downregulated genes, identifying key pathways for T2D pathogenesis, including defective insulin secretion, {SREBP} signaling and oxidative stress. We also compared these results with previous data of human T2D β-cells from laser capture microdissection and diabetic rat islets, revealing shared β-cell genes. Overall, the present study encourages the pursuit of single β-cell {RNA}-seq analysis, preventing presently identified sources of variability, to identify transcriptomic changes associated with human T2D and underscores specific traits of dysfunctional β-cells across different models and techniques.}, pages = {lqaa097}, number = {4}, journaltitle = {{NAR} genomics and bioinformatics}, shortjournal = {{NAR} Genom Bioinform}, author = {Bosi, Emanuele and Marselli, Lorella and De Luca, Carmela and Suleiman, Mara and Tesi, Marta and Ibberson, Mark and Eizirik, Decio L. and Cnop, Miriam and Marchetti, Piero}, date = {2020-12}, pmid = {33575641}, pmcid = {PMC7679065}, keywords = {{WP}4, {WP}5}, }