Human axial progenitors generate trunk neural crest cells in vitro
- University of Sheffield, United Kingdom
- High Performance Computing and Networking Institute (ICAR), National Research Council of Italy (CNR), Italy
- Technische Universität Dresden, Germany
- University of Cambridge, United Kingdom
- Max Delbrück Center for Molecular Medicine, Germany
- The Francis Crick Institute, United Kingdom
- University of Edinburgh, United Kingdom
Abstract
The neural crest (NC) is a multipotent embryonic cell population that generates distinct cell types in an axial position-dependent manner. The production of NC cells from human pluripotent stem cells (hPSCs) is a valuable approach to study human NC biology. However, the origin of human trunk NC remains undefined and current in vitro differentiation strategies induce only a modest yield of trunk NC cells. Here we show that hPSC-derived axial progenitors, the posteriorly-located drivers of embryonic axis elongation, give rise to trunk NC cells and their derivatives. Moreover, we define the molecular signatures associated with the emergence of human NC cells of distinct axial identities in vitro. Collectively, our findings indicate that there are two routes toward a human post-cranial NC state: the birth of cardiac and vagal NC is facilitated by retinoic acid-induced posteriorisation of an anterior precursor whereas trunk NC arises within a pool of posterior axial progenitors.
Data availability
The microarray and RNAseq data have been deposited to GEO (GSE109267 and GSE110608).
Article and author information
Author details
James O S Hackland
Konstantinos Anastassiadis
Anestis Tsakiridis
Funding
Biotechnology and Biological Sciences Research Council (BB/P000444/1)
- Mina Gouti
- Anestis Tsakiridis
Medical Research Council (Mr/K011200/1)
- James Briscoe
- Valerie Wilson
Royal Society (RG160249)
- Anestis Tsakiridis
Cancer Research UK (FC001051)
- James Briscoe
Wellcome (FC001051)
- James Briscoe
Seventh Framework Programme (Plurimes)
- Konstantinos Anastassiadis
- Peter W Andrews
Royal Society
- Stuart L Johnson
Biotechnology and Biological Sciences Research Council (BB/J015539/1)
- Mina Gouti
- Anestis Tsakiridis
Medical Research Council (FC001051)
- James Briscoe
- Valerie Wilson
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Reviewing Editor
- Richard M White, Memorial Sloan Kettering Cancer Center, United States
Version history
- Received: February 8, 2018
- Accepted: August 9, 2018
- Accepted Manuscript published: August 10, 2018 (version 1)
- Version of Record published: August 20, 2018 (version 2)
Copyright
© 2018, Frith 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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Human axial progenitors generate trunk neural crest cells in vitro
eLife 7:e35786.
https://doi.org/10.7554/eLife.35786
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