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
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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DOI：
10.1016/j.scr.2019.101563
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发表时间：
2019-10-01
影响因子：
1.2
通讯作者：
Bohaciakova, Dasa
中科院分区：
文献类型：
--
作者：
Fedorova, Veronika;Vanova, Tereza;Bohaciakova, Dasa
神经管的发育已经在体外使用人类多能干细胞（hPSC）进行了广泛建模，所述人类多能干细胞能够形成称为神经管的放射状组织的细胞结构。虽然大量的研究已经完成使用神经rotoplasty，研究只是不充分地解决rotoplasty是如何形成的，以及参与其形成的分子机制和途径是什么。在这里，我们解决这个问题，通过详细分析的表达的多能性和分化相关蛋白在早期开始分化的hPSC向神经roximus。此外，我们表明，BMP信号可能有助于形成复杂的神经丛，其抑制导致PAX6，SOX 2和SOX 1蛋白的表达和玫瑰花结形态的改变。最后，我们提供的证据表明，在体外的神经形成的机制是让人想起的过程中，而不是在体内的初级神经形成的次级神经形成。由于继发性神经形成是一个很大程度上未探索的过程，它的理解将最终有助于预防人类尾神经管缺陷的方法的发展。
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.