Cargando…
Insulin-producing β-cells regenerate ectopically from a mesodermal origin under the perturbation of hemato-endothelial specification
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 mes...
Autores principales: | , , , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
eLife Sciences Publications, Ltd
2021
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8370765/ https://www.ncbi.nlm.nih.gov/pubmed/34403334 http://dx.doi.org/10.7554/eLife.65758 |
_version_ | 1783739502390411264 |
---|---|
author | Liu, Ka-Cheuk Villasenor, Alethia Bertuzzi, Maria Schmitner, Nicole Radros, Niki Rautio, Linn Mattonet, Kenny Matsuoka, Ryota L Reischauer, Sven Stainier, Didier YR Andersson, Olov |
author_facet | Liu, Ka-Cheuk Villasenor, Alethia Bertuzzi, Maria Schmitner, Nicole Radros, Niki Rautio, Linn Mattonet, Kenny Matsuoka, Ryota L Reischauer, Sven Stainier, Didier YR Andersson, Olov |
author_sort | Liu, Ka-Cheuk |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-8370765 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | eLife Sciences Publications, Ltd |
record_format | MEDLINE/PubMed |
spelling | pubmed-83707652021-08-18 Insulin-producing β-cells regenerate ectopically from a mesodermal origin under the perturbation of hemato-endothelial specification Liu, Ka-Cheuk Villasenor, Alethia Bertuzzi, Maria Schmitner, Nicole Radros, Niki Rautio, Linn Mattonet, Kenny Matsuoka, Ryota L Reischauer, Sven Stainier, Didier YR Andersson, Olov eLife Developmental Biology 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. eLife Sciences Publications, Ltd 2021-08-17 /pmc/articles/PMC8370765/ /pubmed/34403334 http://dx.doi.org/10.7554/eLife.65758 Text en © 2021, Liu et al https://creativecommons.org/licenses/by/4.0/This article is distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use and redistribution provided that the original author and source are credited. |
spellingShingle | Developmental Biology Liu, Ka-Cheuk Villasenor, Alethia Bertuzzi, Maria Schmitner, Nicole Radros, Niki Rautio, Linn Mattonet, Kenny Matsuoka, Ryota L Reischauer, Sven Stainier, Didier YR Andersson, Olov Insulin-producing β-cells regenerate ectopically from a mesodermal origin under the perturbation of hemato-endothelial specification |
title | Insulin-producing β-cells regenerate ectopically from a mesodermal origin under the perturbation of hemato-endothelial specification |
title_full | Insulin-producing β-cells regenerate ectopically from a mesodermal origin under the perturbation of hemato-endothelial specification |
title_fullStr | Insulin-producing β-cells regenerate ectopically from a mesodermal origin under the perturbation of hemato-endothelial specification |
title_full_unstemmed | Insulin-producing β-cells regenerate ectopically from a mesodermal origin under the perturbation of hemato-endothelial specification |
title_short | Insulin-producing β-cells regenerate ectopically from a mesodermal origin under the perturbation of hemato-endothelial specification |
title_sort | insulin-producing β-cells regenerate ectopically from a mesodermal origin under the perturbation of hemato-endothelial specification |
topic | Developmental Biology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8370765/ https://www.ncbi.nlm.nih.gov/pubmed/34403334 http://dx.doi.org/10.7554/eLife.65758 |
work_keys_str_mv | AT liukacheuk insulinproducingbcellsregenerateectopicallyfromamesodermaloriginundertheperturbationofhematoendothelialspecification AT villasenoralethia insulinproducingbcellsregenerateectopicallyfromamesodermaloriginundertheperturbationofhematoendothelialspecification AT bertuzzimaria insulinproducingbcellsregenerateectopicallyfromamesodermaloriginundertheperturbationofhematoendothelialspecification AT schmitnernicole insulinproducingbcellsregenerateectopicallyfromamesodermaloriginundertheperturbationofhematoendothelialspecification AT radrosniki insulinproducingbcellsregenerateectopicallyfromamesodermaloriginundertheperturbationofhematoendothelialspecification AT rautiolinn insulinproducingbcellsregenerateectopicallyfromamesodermaloriginundertheperturbationofhematoendothelialspecification AT mattonetkenny insulinproducingbcellsregenerateectopicallyfromamesodermaloriginundertheperturbationofhematoendothelialspecification AT matsuokaryotal insulinproducingbcellsregenerateectopicallyfromamesodermaloriginundertheperturbationofhematoendothelialspecification AT reischauersven insulinproducingbcellsregenerateectopicallyfromamesodermaloriginundertheperturbationofhematoendothelialspecification AT stainierdidieryr insulinproducingbcellsregenerateectopicallyfromamesodermaloriginundertheperturbationofhematoendothelialspecification AT anderssonolov insulinproducingbcellsregenerateectopicallyfromamesodermaloriginundertheperturbationofhematoendothelialspecification |