Please use this identifier to cite or link to this item: https://hdl.handle.net/10356/171807
Title: Molecular phenotyping of single pancreatic islet leader beta cells by "Flash-Seq"
Authors: Chabosseau, Pauline
Yong, Fiona
Delgadillo-Silva, Luis F.
Lee, Eun Young
Melhem, Rana
Li, Shiying
Gandhi, Nidhi
Wastin, Jules
Noriega, Livia Lopez
Leclerc, Isabelle
Ali, Yusuf
Hughes, Jing W.
Sladek, Robert
Martinez-Sanchez, Aida
Rutter, Guy A.
Keywords: Science::Medicine
Issue Date: 2023
Source: Chabosseau, 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.2023.121436
Journal: Life Sciences 
Abstract: Aims: 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.
URI: https://hdl.handle.net/10356/171807
ISSN: 0024-3205
DOI: 10.1016/j.lfs.2023.121436
Schools: Lee Kong Chian School of Medicine (LKCMedicine) 
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/).
Fulltext Permission: open
Fulltext Availability: With Fulltext
Appears in Collections:LKCMedicine Journal Articles

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