Human axial progenitors generate trunk neural crest cells in vitro

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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.
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Funding Information
  • University of Sheffield (Biomedical Science Departmental PhD studentship)
  • Seventh Framework Programme (FP7/2007-2013 agreement no. 602423 (Plurimes))
  • Biotechnology and Biological Sciences Research Council (BB/J015539/1)
  • Cancer Research UK (FC001051)
  • Wellcome (FC001051)
  • Medical Research Council (FC001051)
  • Medical Research Council (Mr/K011200/1)
  • Royal Society (University Research Fellow)
  • Ministero dell’Istruzione, dell’Università e della Ricerca (Iteromics Flagship project)
  • Biotechnology and Biological Sciences Research Council (BB/P000444/1)
  • Royal Society (RG160249)
  • Little Princess Trust and Children's Cancer and Leukaemia Group (CCLGA 2016 01)

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