Reconstructing human pancreatic differentiation by mapping specific cell populations during development
- Cochin Institute, France
- Faculty of Health Sciences, University of Copenhagen, Denmark
- Novo Nordisk A/S, Denmark
Abstract
Information remains scarce on human development compared to animal models. Here, we reconstructed human fetal pancreatic differentiation using cell surface markers. We demonstrate that at 7 weeks of development, the glycoprotein 2 (GP2) marks a multipotent cell population that will differentiate into the acinar, ductal or endocrine lineages. Development towards the acinar lineage is paralleled by an increase in GP2 expression. Conversely, a subset of the GP2+ population undergoes endocrine differentiation by down-regulating GP2 and CD142 and turning on NEUROG3, a marker of endocrine differentiation. Endocrine maturation progresses by up-regulating SUSD2 and lowering ECAD levels. Finally, in vitro differentiation of pancreatic endocrine cells derived from human pluripotent stem cells mimics key in vivo events. Our work paves the way to extend our understanding of the origin of mature human pancreatic cell types and how such lineage decisions are regulated.
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Author details
Raphaël Scharfmann
Funding
European commition's seventh framework program (602587)
- Raphaël Scharfmann
Innovative medicines initiative (115439)
- Raphaël Scharfmann
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Reviewing Editor
- Neil A Hanley, University of Manchester, United Kingdom
Version history
- Received: April 7, 2017
- Accepted: July 17, 2017
- Accepted Manuscript published: July 21, 2017 (version 1)
- Version of Record published: August 2, 2017 (version 2)
Copyright
© 2017, Ramond et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Reconstructing human pancreatic differentiation by mapping specific cell populations during development
eLife 6:e27564.
https://doi.org/10.7554/eLife.27564
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