PUBLICATION
Decoding pancreatic endocrine cell differentiation and β cell regeneration in zebrafish
- Authors
- Mi, J., Liu, K.C., Andersson, O.
- ID
- ZDB-PUB-230819-46
- Date
- 2023
- Source
- Science advances 9: eadf5142eadf5142 (Journal)
- Registered Authors
- Liu, Ka-Cheuk
- Keywords
- none
- Datasets
- GEO:GSE226841
- MeSH Terms
-
- Animals
- Cell Differentiation
- Endocrine Cells*
- Humans
- Insulin-Secreting Cells*
- Mice
- Regeneration
- Zebrafish
- PubMed
- 37595046 Full text @ Sci Adv
Citation
Mi, J., Liu, K.C., Andersson, O. (2023) Decoding pancreatic endocrine cell differentiation and β cell regeneration in zebrafish. Science advances. 9:eadf5142eadf5142.
Abstract
In contrast to mice, zebrafish have an exceptional yet elusive ability to replenish lost β cells in adulthood. Understanding this framework would provide mechanistic insights for β cell regeneration, which may be extrapolated to humans. Here, we characterize a krt4-expressing ductal cell type, which is distinct from the putative Notch-responsive cells, showing neogenic competence and giving rise to the majority of endocrine cells during postembryonic development. Furthermore, we demonstrate a marked ductal remodeling process featuring a Notch-responsive to krt4+ luminal duct transformation during late development, indicating several origins of krt4+ ductal cells displaying similar transcriptional patterns. Single-cell transcriptomics upon a series of time points during β cell regeneration unveil a previously unrecognized dlb+ transitional endocrine precursor cell, distinct regulons, and a differentiation trajectory involving cellular shuffling through differentiation and dedifferentiation dynamics. These results establish a model of zebrafish pancreatic endocrinogenesis and highlight key values of zebrafish for translational studies of β cell regeneration.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping