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http://purl.uniprot.org/citations/37870650http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/37870650http://www.w3.org/2000/01/rdf-schema#comment"

Aims/hypothesis

Glucagon-expressing pancreatic alpha cells have attracted much attention for their plasticity to transdifferentiate into insulin-producing beta cells; however, it remains unclear precisely when, and from where, alpha cells emerge and what regulates alpha cell fate. We therefore explored the spatial and transcriptional heterogeneity of alpha cell differentiation using a novel time-resolved reporter system.

Methods

We established the mouse model, 'Gcg-Timer', in which newly generated alpha cells can be distinguished from more-differentiated cells by their fluorescence. Fluorescence imaging and transcriptome analysis were performed with Gcg-Timer mice during the embryonic and postnatal stages.

Results

Fluorescence imaging and flow cytometry demonstrated that green fluorescence-dominant cells were present in Gcg-Timer mice at the embryonic and neonatal stages but not after 1 week of age, suggesting that alpha cell neogenesis occurs during embryogenesis and early neonatal stages under physiological conditions. Transcriptome analysis of Gcg-Timer embryos revealed that the mRNAs related to angiogenesis were enriched in newly generated alpha cells. Histological analysis revealed that some alpha cells arise close to the pancreatic ducts, whereas the others arise away from the ducts and adjacent to the blood vessels. Notably, when the glucagon signal was suppressed by genetic ablation or by chemicals, such as neutralising glucagon antibody, green-dominant cells emerged again in adult mice.

Conclusions/interpretation

Novel time-resolved analysis with Gcg-Timer reporter mice uncovered spatiotemporal features of alpha cell neogenesis that will enhance our understanding of cellular identity and plasticity within the islets.

Data availability

Raw and processed RNA sequencing data for this study has been deposited in the Gene Expression Omnibus under accession number GSE229090."xsd:string
http://purl.uniprot.org/citations/37870650http://purl.org/dc/terms/identifier"doi:10.1007/s00125-023-06028-w"xsd:string
http://purl.uniprot.org/citations/37870650http://purl.uniprot.org/core/author"Ogihara T."xsd:string
http://purl.uniprot.org/citations/37870650http://purl.uniprot.org/core/author"Oshima S."xsd:string
http://purl.uniprot.org/citations/37870650http://purl.uniprot.org/core/author"Hiraoka Y."xsd:string
http://purl.uniprot.org/citations/37870650http://purl.uniprot.org/core/author"Nishida Y."xsd:string
http://purl.uniprot.org/citations/37870650http://purl.uniprot.org/core/author"Sasaki S."xsd:string
http://purl.uniprot.org/citations/37870650http://purl.uniprot.org/core/author"Taguchi T."xsd:string
http://purl.uniprot.org/citations/37870650http://purl.uniprot.org/core/author"Wakabayashi Y."xsd:string
http://purl.uniprot.org/citations/37870650http://purl.uniprot.org/core/author"Iida H."xsd:string
http://purl.uniprot.org/citations/37870650http://purl.uniprot.org/core/author"Okamoto R."xsd:string
http://purl.uniprot.org/citations/37870650http://purl.uniprot.org/core/author"Lynn F.C."xsd:string
http://purl.uniprot.org/citations/37870650http://purl.uniprot.org/core/author"Fujitani Y."xsd:string
http://purl.uniprot.org/citations/37870650http://purl.uniprot.org/core/author"Katahira T."xsd:string
http://purl.uniprot.org/citations/37870650http://purl.uniprot.org/core/author"Watada H."xsd:string
http://purl.uniprot.org/citations/37870650http://purl.uniprot.org/core/author"Suzuki L."xsd:string
http://purl.uniprot.org/citations/37870650http://purl.uniprot.org/core/author"Miyatsuka T."xsd:string
http://purl.uniprot.org/citations/37870650http://purl.uniprot.org/core/author"Himuro M."xsd:string
http://purl.uniprot.org/citations/37870650http://purl.uniprot.org/core/date"2024"xsd:gYear
http://purl.uniprot.org/citations/37870650http://purl.uniprot.org/core/name"Diabetologia"xsd:string
http://purl.uniprot.org/citations/37870650http://purl.uniprot.org/core/pages"156-169"xsd:string
http://purl.uniprot.org/citations/37870650http://purl.uniprot.org/core/title"Novel time-resolved reporter mouse reveals spatial and transcriptional heterogeneity during alpha cell differentiation."xsd:string
http://purl.uniprot.org/citations/37870650http://purl.uniprot.org/core/volume"67"xsd:string
http://purl.uniprot.org/citations/37870650http://www.w3.org/2004/02/skos/core#exactMatchhttp://purl.uniprot.org/pubmed/37870650
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