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

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Authors

FEDOROVÁ Veronika VÁŇOVÁ Tereza ELREFAE Lina Mohamed Bahaael POSPÍŠIL Jakub PETRÁŠOVÁ Martina KOLAJOVÁ Veronika HUDACOVA Zuzana BANIARIOVÁ Jana BARÁK Martin PEŠKOVÁ Lucie BÁRTA Tomáš KAUCKÁ Markéta KILLINGER Michael VEČEŘA Josef BERNATÍK Ondřej ČAJÁNEK Lukáš HŘÍBKOVÁ Hana BOHAČIAKOVÁ Dáša

Year of publication 2019
Type Article in Periodical
Magazine / Source Stem Cell Research
MU Faculty or unit

Faculty of Medicine

Citation
Web https://www.sciencedirect.com/science/article/pii/S187350611930193X?via%3Dihub
Doi http://dx.doi.org/10.1016/j.scr.2019.101563
Keywords BMP; Differentiation; Human embryonic stem cells; Induced pluripotent stem cells; Neural rosettes; Secondary neurulation
Description Development 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 will ultimately assist the development of methods to prevent caudal neural tube defects in humans.
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