Please use this identifier to cite or link to this item: https://hdl.handle.net/10356/171807
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dc.contributor.authorChabosseau, Paulineen_US
dc.contributor.authorYong, Fionaen_US
dc.contributor.authorDelgadillo-Silva, Luis F.en_US
dc.contributor.authorLee, Eun Youngen_US
dc.contributor.authorMelhem, Ranaen_US
dc.contributor.authorLi, Shiyingen_US
dc.contributor.authorGandhi, Nidhien_US
dc.contributor.authorWastin, Julesen_US
dc.contributor.authorNoriega, Livia Lopezen_US
dc.contributor.authorLeclerc, Isabelleen_US
dc.contributor.authorAli, Yusufen_US
dc.contributor.authorHughes, Jing W.en_US
dc.contributor.authorSladek, Roberten_US
dc.contributor.authorMartinez-Sanchez, Aidaen_US
dc.contributor.authorRutter, Guy A.en_US
dc.date.accessioned2023-11-08T05:10:52Z-
dc.date.available2023-11-08T05:10:52Z-
dc.date.issued2023-
dc.identifier.citationChabosseau, P., Yong, F., Delgadillo-Silva, L. F., Lee, E. Y., Melhem, R., Li, S., Gandhi, N., Wastin, J., Noriega, L. L., Leclerc, I., Ali, Y., Hughes, J. W., Sladek, R., Martinez-Sanchez, A. & Rutter, G. A. (2023). Molecular phenotyping of single pancreatic islet leader beta cells by "Flash-Seq". Life Sciences, 316, 121436-. https://dx.doi.org/10.1016/j.lfs.2023.121436en_US
dc.identifier.issn0024-3205en_US
dc.identifier.urihttps://hdl.handle.net/10356/171807-
dc.description.abstractAims: Spatially-organized increases in cytosolic Ca2+ within pancreatic beta cells in the pancreatic islet underlie the stimulation of insulin secretion by high glucose. Recent data have revealed the existence of subpopulations of beta cells including “leaders” which initiate Ca2+ waves. Whether leader cells possess unique molecular features, or localisation, is unknown. Main methods: High speed confocal Ca2+ imaging was used to identify leader cells and connectivity analysis, running under MATLAB and Python, to identify highly connected “hub” cells. To explore transcriptomic differences between beta cell sub-groups, individual leaders or followers were labelled by photo-activation of the cryptic fluorescent protein PA-mCherry and subjected to single cell RNA sequencing (“Flash-Seq”). Key findings: Distinct Ca2+ wave types were identified in individual islets, with leader cells present in 73 % (28 of 38 islets imaged). Scale-free, power law-adherent behaviour was also observed in 29 % of islets, though “hub” cells in these islets did not overlap with leaders. Transcripts differentially expressed (295; padj < 0.05) between leader and follower cells included genes involved in cilium biogenesis and transcriptional regulation. Providing some support for these findings, ADCY6 immunoreactivity tended to be higher in leader than follower cells, whereas cilia number and length tended to be lower in the former. Finally, leader cells were located significantly closer to delta, but not alpha, cells in Euclidian space than were follower cells. Significance: The existence of both a discrete transcriptome and unique localisation implies a role for these features in defining the specialized function of leaders. These data also raise the possibility that localised signalling between delta and leader cells contributes to the initiation and propagation of islet Ca2+ waves.en_US
dc.language.isoenen_US
dc.relation.ispartofLife Sciencesen_US
dc.rights© 2023 The Authors. Published by Elsevier Inc. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).en_US
dc.subjectScience::Medicineen_US
dc.titleMolecular phenotyping of single pancreatic islet leader beta cells by "Flash-Seq"en_US
dc.typeJournal Articleen
dc.contributor.schoolLee Kong Chian School of Medicine (LKCMedicine)en_US
dc.identifier.doi10.1016/j.lfs.2023.121436-
dc.description.versionPublished versionen_US
dc.identifier.pmid36706832-
dc.identifier.scopus2-s2.0-85147277582-
dc.identifier.volume316en_US
dc.identifier.spage121436en_US
dc.subject.keywordsDiabetesen_US
dc.subject.keywordsBeta Cellen_US
dc.description.acknowledgementG.R. was supported by a Wellcome Trust Investigator (212625/Z/ 18/Z) Award, MRC Programme grant (MR/R022259/1), and Diabetes UK (BDA/11/0004210, BDA/15/0005275, BDA 16/0005485) grants, start-up funds from the CRCHUM and a John R. Evans Leaders Award from Innovation Canada. This project has received funding from the European Union's Horizon 2020 research and innovation programme via the Innovative Medicines Initiative 2 Joint Undertaking under grant agreement No. 115881 (RHAPSODY) to G.R. I.L. was supported by a project grant from Diabetes UK (16/0005485). E.L. and J.H. were supported by NIH grants DK115795 and DK127748.en_US
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