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.
Highlights
The neural crest (NC) is a multipotent cell population which arises in the dorsal neural plate/non-neural ectoderm border region during vertebrate embryogenesis
To interrogate the transcriptome changes associated with the induction of such progenitors in a human system and identify the presence of trunk NC precursors, we carried out RNA sequencing (RNAseq) following 3- day treatment of human pluripotent stem cells (hPSCs) with recombinant FGF2 and the WNT agonist/GSK-3 inhibitor CHIR99021 (CHIR)
We found that the transcriptomes of axial progenitors/NMPs and hPSCs were distinct from each other (Figure 1—figure supplement 1A,B) with marked global gene expression changes accompanying the acquisition of an axial progenitor character: 1911 and 1895 genes were significantly up- and down-regulated compared to hPSCs respectively (Supplementary file 1)
Summary
The neural crest (NC) is a multipotent cell population which arises in the dorsal neural plate/non-neural ectoderm border region during vertebrate embryogenesis. Studies utilising chick and amphibian embryos have indicated that different levels of BMP, WNT and FGF signals, emanating from the mesoderm/non-neural ectoderm, orchestrate NC induction and specification (Stuhlmiller and Garcıa-Castro, 2012). This occurs via the action, first of neural plate border-specific transcription factors such as PAX3/7, MSX and ZIC family members, and via definitive NC-specifiers (e.g. SOX9/10) (Simoes-Costa and Bronner, 2015).
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