dc.contributor.author | Oropeza, Daniel | |
dc.contributor.author | Cigliola, Valentina | |
dc.contributor.author | Romero, Agustín | |
dc.contributor.author | Chera, Simona | |
dc.contributor.author | Rodríguez-Seguí, Santiago | |
dc.contributor.author | Herrera, Pedro L. | |
dc.date.accessioned | 2022-04-21T09:00:45Z | |
dc.date.available | 2022-04-21T09:00:45Z | |
dc.date.created | 2022-01-19T18:21:29Z | |
dc.date.issued | 2021 | |
dc.identifier.issn | 1471-2164 | |
dc.identifier.uri | https://hdl.handle.net/11250/2991872 | |
dc.description.abstract | Background
Loss of pancreatic insulin-secreting β-cells due to metabolic or autoimmune damage leads to the development of diabetes. The discovery that α-cells can be efficiently reprogrammed into insulin-secreting cells in mice and humans has opened promising avenues for innovative diabetes therapies. β-cell loss triggers spontaneous reprogramming of only 1–2% of α-cells, limiting the extent of regeneration. Most α-cells are refractory to conversion and their global transcriptomic response to severe β-cell loss as well as the mechanisms opposing their reprogramming into insulin producers are largely unknown. Here, we performed RNA-seq on FAC-sorted α-cells to characterize their global transcriptional responses at different time points after massive β-cell ablation.
Results
Our results show that α-cells undergo stage-specific transcriptional changes 5- and 15-days post-diphtheria toxin (DT)-mediated β-cell ablation. At 5 days, α-cells transiently upregulate various genes associated with interferon signaling and proliferation, including Interferon Induced Protein with Tetratricopeptide Repeats 3 (Ifit3). Subsequently, at 15 days post β-cell ablation, α-cells undergo a transient downregulation of genes from several pathways including Insulin receptor, mTOR and MET signaling.
Conclusions
The results presented here pinpoint novel markers discriminating α-cells at different stages after acute β-cell loss, and highlight additional signaling pathways that are modulated in α-cells in this context. | en_US |
dc.language.iso | eng | en_US |
dc.publisher | BioMed Central | en_US |
dc.rights | Navngivelse 4.0 Internasjonal | * |
dc.rights.uri | http://creativecommons.org/licenses/by/4.0/deed.no | * |
dc.title | Stage-specific transcriptomic changes in pancreatic α-cells after massive β-cell loss | en_US |
dc.type | Journal article | en_US |
dc.type | Peer reviewed | en_US |
dc.description.version | publishedVersion | en_US |
dc.rights.holder | Copyright 2021 The Author(s) | en_US |
dc.source.articlenumber | 585 | en_US |
cristin.ispublished | true | |
cristin.fulltext | original | |
cristin.qualitycode | 1 | |
dc.identifier.doi | 10.1186/s12864-021-07812-x | |
dc.identifier.cristin | 1985342 | |
dc.source.journal | BMC Genomics | en_US |
dc.identifier.citation | BMC Genomics. 2021, 22, 585 | en_US |
dc.source.volume | 22 | en_US |