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

Author:

Liu Ka-Cheuk1ORCID,Villasenor Alethia2,Bertuzzi Maria3,Schmitner Nicole1,Radros Niki4,Rautio Linn1,Mattonet Kenny2ORCID,Matsuoka Ryota L25ORCID,Reischauer Sven26ORCID,Stainier Didier YR2ORCID,Andersson Olov1ORCID

Affiliation:

1. Department of Cell and Molecular Biology, Karolinska Institutet, Stockholm, Sweden

2. Department of Developmental Genetics, Max Planck Institute for Heart and Lung Research, Bad Nauheim, Germany

3. Department of Neuroscience, Karolinska Institutet, Stockholm, Sweden

4. Dermatology and Venereology Division, Department of Medicine (Solna), Karolinska Institutet, Stockholm, Sweden

5. Department of Cardiovascular and Metabolic Sciences, Lerner Research Institute, Cleveland Clinic, Cleveland, United States

6. Cardio-Pulmonary Institute, Frankfurt, Germany; Medical Clinic I, (Cardiology/Angiology) and Campus Kerckhoff, Justus-Liebig-University Giessen, Giessen, Germany

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.

Funder

Ragnar Söderbergs stiftelse

Max Planck Society

Vetenskapsrådet

Novo Nordisk Fonden

Karolinska Institutetvia SRP Diabetes & StratRegen

H2020 European Research Council

Publisher

eLife Sciences Publications, Ltd

Subject

General Immunology and Microbiology,General Biochemistry, Genetics and Molecular Biology,General Medicine,General Neuroscience

同舟云学术

1.学者识别学者识别

2.学术分析学术分析

3.人才评估人才评估

"同舟云学术"是以全球学者为主线,采集、加工和组织学术论文而形成的新型学术文献查询和分析系统,可以对全球学者进行文献检索和人才价值评估。用户可以通过关注某些学科领域的顶尖人物而持续追踪该领域的学科进展和研究前沿。经过近期的数据扩容,当前同舟云学术共收录了国内外主流学术期刊6万余种,收集的期刊论文及会议论文总量共计约1.5亿篇,并以每天添加12000余篇中外论文的速度递增。我们也可以为用户提供个性化、定制化的学者数据。欢迎来电咨询!咨询电话:010-8811{复制后删除}0370

www.globalauthorid.com

TOP

Copyright © 2019-2024 北京同舟云网络信息技术有限公司
京公网安备11010802033243号  京ICP备18003416号-3