Differentiation of neural rosettes from human pluripotent stem cells in vitro is sequentially regulated on a molecular level and accomplished by the mechanism reminiscent of secondary neurulation

Publication date: Available online 29 August 2019Source: Stem Cell ResearchAuthor(s): Veronika Fedorova, Tereza Vanova, Lina Elrefae, Jakub Pospisil, Martina Petrasova, Veronika Kolajova, Zuzana Hudacova, Jana Baniariova, Martin Barak, Lucie Peskova, Tomas Barta, Marketa Kaucka, Michael Killinger, Josef Vecera, Ondrej Bernatik, Lukas Cajanek, Hana Hribkova, Dasa BohaciakovaAbstractDevelopment of neural tube has been extensively modeled in vitro using human pluripotent stem cells (hPSCs) that are able to form radially organized cellular structures called neural rosettes. While a great amount of research has been done using neural rosettes, studies have only inadequately addressed how rosettes are formed and what the molecular mechanisms and pathways involved in their formation are. Here we address this question by detailed analysis of the expression of pluripotency and differentiation-associated proteins during the early onset of differentiation of hPSCs towards neural rosettes. Additionally, we show that the BMP signaling is likely contributing to the formation of the complex cluster of neural rosettes and its inhibition leads to the altered expression of PAX6, SOX2 and SOX1 proteins and the rosette morphology. Finally, we provide evidence that the mechanism of neural rosettes formation in vitro is reminiscent of the process of secondary neurulation rather than that of primary neurulation in vivo. Since secondary neurulation is a largely unexplored process, its understanding ...
Source: Stem Cell Research - Category: Stem Cells Source Type: research