Human alpha cell transcriptomic signatures of types 1 and 2 diabetes highlight disease-specific dysfunction pathways
Summary: Although glucagon secretion is perturbed in both T1D and T2D, the pathophysiological changes in individual pancreatic alpha cells are still obscure. Using recently curated single-cell RNASeq data from T1D or T2D donors and their controls, we identified alpha cell transcriptomic alterations...
| Main Authors: | , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2022-10-01
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| Series: | iScience |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2589004222013281 |
| _version_ | 1811268112606035968 |
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| author | Emanuele Bosi Piero Marchetti Guy Allen Rutter Decio Laks Eizirik |
| author_facet | Emanuele Bosi Piero Marchetti Guy Allen Rutter Decio Laks Eizirik |
| author_sort | Emanuele Bosi |
| collection | DOAJ |
| description | Summary: Although glucagon secretion is perturbed in both T1D and T2D, the pathophysiological changes in individual pancreatic alpha cells are still obscure. Using recently curated single-cell RNASeq data from T1D or T2D donors and their controls, we identified alpha cell transcriptomic alterations consistent with both common and discrete pathways. Although alterations in alpha cell identity gene (ARX, MAFB) expression were conserved, cytokine-regulated genes and genes involved in glucagon biosynthesis and processing were up-regulated in T1D. Conversely, mitochondrial genes associated with ROS (COX7B, NQO2) were dysregulated in T2D. Additionally, T1D alpha cells displayed altered expression of autoimmune-induced ER stress genes (ERLEC1, HSP90), whilst those from T2D subjects showed modified glycolytic and citrate cycle gene (LDHA?, PDHB, PDK4) expression. Thus, despite conserved alterations related to loss of function, alpha cells display disease-specific gene signatures which may be secondary to the main pathogenic events in each disease, namely immune- or metabolism-mediated-stress, in T1D and T2D, respectively. |
| first_indexed | 2024-04-12T21:15:54Z |
| format | Article |
| id | doaj.art-3d50bb63ec9c47b0a381164e3b5b3cb8 |
| institution | Directory Open Access Journal |
| issn | 2589-0042 |
| language | English |
| last_indexed | 2024-04-12T21:15:54Z |
| publishDate | 2022-10-01 |
| publisher | Elsevier |
| record_format | Article |
| series | iScience |
| spelling | doaj.art-3d50bb63ec9c47b0a381164e3b5b3cb82022-12-22T03:16:26ZengElsevieriScience2589-00422022-10-012510105056Human alpha cell transcriptomic signatures of types 1 and 2 diabetes highlight disease-specific dysfunction pathwaysEmanuele Bosi0Piero Marchetti1Guy Allen Rutter2Decio Laks Eizirik3Department of Experimental and Clinical Medicine, Pancreatic Islets Laboratory, University of Pisa, Pisa, Italy; Department of Earth, Environmental and Life Sciences (DISTAV), University of Genoa, Genova, Italy; Corresponding authorDepartment of Experimental and Clinical Medicine, Pancreatic Islets Laboratory, University of Pisa, Pisa, ItalyCR-CHUM and Université de Montréal, Montréal, QC, Canada; Section of Cell Biology and Functional Genomics, Division of Diabetes, Endocrinology and Metabolism, Department of Metabolism, Digestion and Reproduction, Imperial College London, London, UK; Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore, SingaporeULB Center for Diabetes Research, Université Libre de Bruxelles, Brussels, BelgiumSummary: Although glucagon secretion is perturbed in both T1D and T2D, the pathophysiological changes in individual pancreatic alpha cells are still obscure. Using recently curated single-cell RNASeq data from T1D or T2D donors and their controls, we identified alpha cell transcriptomic alterations consistent with both common and discrete pathways. Although alterations in alpha cell identity gene (ARX, MAFB) expression were conserved, cytokine-regulated genes and genes involved in glucagon biosynthesis and processing were up-regulated in T1D. Conversely, mitochondrial genes associated with ROS (COX7B, NQO2) were dysregulated in T2D. Additionally, T1D alpha cells displayed altered expression of autoimmune-induced ER stress genes (ERLEC1, HSP90), whilst those from T2D subjects showed modified glycolytic and citrate cycle gene (LDHA?, PDHB, PDK4) expression. Thus, despite conserved alterations related to loss of function, alpha cells display disease-specific gene signatures which may be secondary to the main pathogenic events in each disease, namely immune- or metabolism-mediated-stress, in T1D and T2D, respectively.http://www.sciencedirect.com/science/article/pii/S2589004222013281Biological sciencesbioinformaticstranscriptomics |
| spellingShingle | Emanuele Bosi Piero Marchetti Guy Allen Rutter Decio Laks Eizirik Human alpha cell transcriptomic signatures of types 1 and 2 diabetes highlight disease-specific dysfunction pathways iScience Biological sciences bioinformatics transcriptomics |
| title | Human alpha cell transcriptomic signatures of types 1 and 2 diabetes highlight disease-specific dysfunction pathways |
| title_full | Human alpha cell transcriptomic signatures of types 1 and 2 diabetes highlight disease-specific dysfunction pathways |
| title_fullStr | Human alpha cell transcriptomic signatures of types 1 and 2 diabetes highlight disease-specific dysfunction pathways |
| title_full_unstemmed | Human alpha cell transcriptomic signatures of types 1 and 2 diabetes highlight disease-specific dysfunction pathways |
| title_short | Human alpha cell transcriptomic signatures of types 1 and 2 diabetes highlight disease-specific dysfunction pathways |
| title_sort | human alpha cell transcriptomic signatures of types 1 and 2 diabetes highlight disease specific dysfunction pathways |
| topic | Biological sciences bioinformatics transcriptomics |
| url | http://www.sciencedirect.com/science/article/pii/S2589004222013281 |
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