| RRC ID |
75868
|
| 著者 |
Liu KC, Villasenor A, Bertuzzi M, Schmitner N, Radros N, Rautio L, Mattonet K, Matsuoka RL, Reischauer S, Stainier DY, Andersson O.
|
| タイトル |
Insulin-producing β-cells regenerate ectopically from a mesodermal origin under the perturbation of hemato-endothelial specification.
|
| ジャーナル |
Elife
|
| 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.
|
| 巻・号 |
10
|
| 公開日 |
2021-8-17
|
| DOI |
10.7554/eLife.65758
|
| PII |
65758
|
| PMID |
34403334
|
| PMC |
PMC8370765
|
| MeSH |
Animals
Cell Differentiation*
Endothelium / physiology
Insulin-Secreting Cells / physiology*
Insulins / metabolism
Mesoderm / embryology*
Regeneration*
Zebrafish / embryology*
Zebrafish / physiology
|
| IF |
7.08
|
| リソース情報 |
| ゼブラフィッシュ |
UAS:GFP |
