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ID 117216
Author
Fukaishi, Takahiro Gunma University|Tokyo Medical and Dental University
Nakagawa, Yuko Gunma University
Fukunaka, Ayako Gunma University
Sato, Takashi Gunma University
Hara, Akemi Juntendo University|Saitama Medical University
Nakao, Keiko Saitama Medical University
Saito, Michiko Nara Institute of Science and Technology|Kyoto Pharmaceutical University
Kohno, Kenji Nara Institute of Science and Technology
Miyatsuka, Takeshi Juntendo University
Matsuoka, Taka-aki Wakayama Medical University
Yamada, Tetsuya Tokyo Medical and Dental University
Watada, Hirotaka Juntendo University
Fujitani, Yoshio Gunma University
Keywords
Beta cell heterogeneity
Ca2+ imaging
Diphtheria toxin
GLUT2
Pancreatic polypeptide
Ppy
Single-cell RNA sequence
Streptozotocin
TSPAN8
UCN3
Content Type
Journal Article
Description
Aims/hypothesis
Pancreatic polypeptide (PP) cells, which secrete PP (encoded by the Ppy gene), are a minor population of pancreatic endocrine cells. Although it has been reported that the loss of beta cell identity might be associated with beta-to-PP cell-fate conversion, at present, little is known regarding the characteristics of Ppy-lineage cells.
Methods
We used Ppy-Cre driver mice and a PP-specific monoclonal antibody to investigate the association between Ppy-lineage cells and beta cells. The molecular profiles of endocrine cells were investigated by single-cell transcriptome analysis and the glucose responsiveness of beta cells was assessed by Ca2+ imaging. Diabetic conditions were experimentally induced in mice by either streptozotocin or diphtheria toxin.
Results
Ppy-lineage cells were found to contribute to the four major types of endocrine cells, including beta cells. Ppy-lineage beta cells are a minor subpopulation, accounting for 12–15% of total beta cells, and are mostly (81.2%) localised at the islet periphery. Unbiased single-cell analysis with a Ppy-lineage tracer demonstrated that beta cells are composed of seven clusters, which are categorised into two groups (i.e. Ppy-lineage and non-Ppy-lineage beta cells). These subpopulations of beta cells demonstrated distinct characteristics regarding their functionality and gene expression profiles. Ppy-lineage beta cells had a reduced glucose-stimulated Ca2+ signalling response and were increased in number in experimental diabetes models.
Conclusions/interpretation
Our results indicate that an unexpected degree of beta cell heterogeneity is defined by Ppy gene activation, providing valuable insight into the homeostatic regulation of pancreatic islets and future therapeutic strategies against diabetes.
Journal Title
Diabetologia
ISSN
0012186X
14320428
NCID
AA00628104
Publisher
Springer Nature|European Association for the Study of Diabetes
Volume
64
Issue
12
Start Page
2803
End Page
2816
Published Date
2021-09-09
Rights
This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.
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DOI (Published Version)
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language
eng
TextVersion
Publisher
departments
Institute of Advanced Medical Sciences