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dc.contributor.author
Oropeza, Daniel
dc.contributor.author
Cigliola, Valentina
dc.contributor.author
Romero, Agustín
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dc.contributor.author
Chera, Simona
dc.contributor.author
Rodríguez Seguí, Santiago Andrés
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dc.contributor.author
Herrera, Pedro L.
dc.date.available
2022-12-22T15:04:48Z
dc.date.issued
2021-08
dc.identifier.citation
Oropeza, Daniel; Cigliola, Valentina; Romero, Agustín; Chera, Simona; Rodríguez Seguí, Santiago Andrés; et al.; Stage-specific transcriptomic changes in pancreatic α-cells after massive β-cell loss; BioMed Central; BMC Genomics; 22; 1; 8-2021; 1-14
dc.identifier.issn
1471-2164
dc.identifier.uri
http://hdl.handle.net/11336/182187
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.
dc.format
application/pdf
dc.language.iso
eng
dc.publisher
BioMed Central
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dc.rights
info:eu-repo/semantics/openAccess
dc.rights.uri
https://creativecommons.org/licenses/by/2.5/ar/
dc.subject
ALPHA CELL
dc.subject
BETA CELL
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CONVERSION
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IFIT3
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PANCREAS
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PANCREATIC ISLET
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PLASTICITY
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REGENERATION
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RNA-SEQ
dc.subject
TRANSCRIPTOME
dc.subject.classification
Bioquímica y Biología Molecular
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dc.subject.classification
Ciencias Biológicas
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dc.subject.classification
CIENCIAS NATURALES Y EXACTAS
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dc.title
Stage-specific transcriptomic changes in pancreatic α-cells after massive β-cell loss
dc.type
info:eu-repo/semantics/article
dc.type
info:ar-repo/semantics/artículo
dc.type
info:eu-repo/semantics/publishedVersion
dc.date.updated
2022-09-23T14:25:46Z
dc.journal.volume
22
dc.journal.number
1
dc.journal.pagination
1-14
dc.journal.pais
Reino Unido
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dc.journal.ciudad
Londres
dc.description.fil
Fil: Oropeza, Daniel. University Of Geneva (ug);
dc.description.fil
Fil: Cigliola, Valentina. University Of Geneva (ug);
dc.description.fil
Fil: Romero, Agustín. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Fisiología, Biología Molecular y Neurociencias. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Fisiología, Biología Molecular y Neurociencias; Argentina
dc.description.fil
Fil: Chera, Simona. University Of Geneva (ug);
dc.description.fil
Fil: Rodríguez Seguí, Santiago Andrés. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Fisiología, Biología Molecular y Neurociencias. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Fisiología, Biología Molecular y Neurociencias; Argentina
dc.description.fil
Fil: Herrera, Pedro L.. University Of Geneva (ug);
dc.journal.title
BMC Genomics
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dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/url/https://bmcgenomics.biomedcentral.com/articles/10.1186/s12864-021-07812-x
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/doi/http://dx.doi.org/10.1186/s12864-021-07812-x
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