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  Insulin-producing beta-cells regenerate ectopically from a mesodermal origin under the perturbation of hemato-endothelial specification

Liu, K.-C., Villasenor, A., Bertuzzi, M., Schmitner, N., Radros, N., Rautio, L., et al. (2021). Insulin-producing beta-cells regenerate ectopically from a mesodermal origin under the perturbation of hemato-endothelial specification. ELIFE, 10: e65758. doi:10.7554/eLife.65758.

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 Creators:
Liu, Ka-Cheuk, Author
Villasenor, Alethia1, Author           
Bertuzzi, Maria, Author
Schmitner, Nicole, Author
Radros, Niki, Author
Rautio, Linn, Author
Mattonet, Kenny1, Author           
Matsuoka, Ryota L.1, Author           
Reischauer, Sven1, Author           
Stainier, Didier Y. R.1, Author           
Andersson, Olov, Author
Affiliations:
1Developmental Genetics, Max Planck Institute for Heart and Lung Research, Max Planck Society, ou_2591697              

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Free keywords: TRANSCRIPTION FACTOR; DIRECT CONVERSION; ZEBRAFISH GENE; EXPRESSION; FIBROBLASTS; SUPPRESSION; PROTEIN; CLOCHE; PANCREAS; PROMOTERLife Sciences & Biomedicine - Other Topics;
 Abstract: To investigate the role of the vasculature in pancreatic beta-cell regeneration, we crossed a zebrafish beta-cell ablation model into the avascular npas4l mutant (i.e. cloche). Surprisingly, beta-cell regeneration increased markedly in npas4l mutants owing to the ectopic differentiation of beta-cell in the mesenchyme, a phenotype not previously reported in any models. The ectopic beta-cell expressed endocrine markers of pancreatic beta-cell, and also responded to glucose with increased calcium influx. Through lineage tracing, we determined that the vast majority of these ectopic beta-cell has a mesodermal origin. Notably, ectopic beta-cell 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 beta-cell, which are normally endodermal in origin. Understanding the restriction of this differentiation plasticity will help exploit an alternative source for beta-cell regeneration.

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Language(s): eng - English
 Dates: 2021-08-17
 Publication Status: Published online
 Pages: 23
 Publishing info: -
 Table of Contents: -
 Rev. Type: -
 Identifiers: ISI: 000687045200001
DOI: 10.7554/eLife.65758
PMID: 34403334
 Degree: -

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Title: ELIFE
Source Genre: Journal
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Publ. Info: SHERATON HOUSE, CASTLE PARK, CAMBRIDGE, CB3 0AX, ENGLAND : ELIFE SCIENCES PUBLICATIONS LTD
Pages: - Volume / Issue: 10 Sequence Number: e65758 Start / End Page: - Identifier: ISSN: 2050-084X