PUBLICATION
Insulin-producing β-cells regenerate ectopically from a mesodermal origin under the perturbation of hemato-endothelial specification
- Authors
- Liu, K.C., Villasenor, A., Bertuzzi, M., Schmitner, N., Radros, N., Rautio, L., Mattonet, K., Matsuoka, R.L., Reischauer, S., Stainier, D.Y., Andersson, O.
- ID
- ZDB-PUB-210818-9
- Date
- 2021
- Source
- eLIFE 10: (Journal)
- Registered Authors
- Liu, Ka-Cheuk, Matsuoka, Ryota, Reischauer, Sven, Stainier, Didier
- Keywords
- beta-cell regeneration, cellular origin, developmental biology, differentiation, ectopic beta-cells, regenerative medicine, stem cells, zebrafish
- MeSH Terms
-
- Animals
- Cell Differentiation*
- Endothelium/physiology
- Insulin-Secreting Cells/physiology*
- Insulins/metabolism
- Mesoderm/embryology*
- Regeneration*
- Zebrafish/embryology*
- Zebrafish/physiology
- PubMed
- 34403334 Full text @ Elife
Citation
Liu, K.C., Villasenor, A., Bertuzzi, M., Schmitner, N., Radros, N., Rautio, L., Mattonet, K., Matsuoka, R.L., Reischauer, S., Stainier, D.Y., Andersson, O. (2021) Insulin-producing β-cells regenerate ectopically from a mesodermal origin under the perturbation of hemato-endothelial specification. eLIFE. 10:.
Abstract
To investigate the role of the vasculature in pancreatic β-cell regeneration, we crossed a zebrafish β-cell ablation model into the avascular npas4l mutant (i.e. cloche). Surprisingly, β-cell regeneration increased markedly in npas4l mutants owing to the ectopic differentiation of β-cells in the mesenchyme, a phenotype not previously reported in any models. The ectopic β-cells expressed endocrine markers of pancreatic β-cells, and also responded to glucose with increased calcium influx. Through lineage tracing, we determined that the vast majority of these ectopic β-cells has a mesodermal origin. Notably, ectopic β-cells were found in npas4l mutants as well as following knockdown of the endothelial/myeloid determinant Etsrp. Together, these data indicate that under the perturbation of endothelial/myeloid specification, mesodermal cells possess a remarkable plasticity enabling them to form β-cells, which are normally endodermal in origin. Understanding the restriction of this differentiation plasticity will help exploit an alternative source for β-cell regeneration.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping