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过表达Lhx1的P19细胞通过重现胚胎发育途径分化为定形内胚层。

P19 Cells Overexpressing Lhx1 Differentiate into the Definitive Endoderm by Recapitulating an Embryonic Developmental Pathway.

作者信息

Hasegawa Akira, Shirayoshi Yasuaki

机构信息

Division of Regenerative Medicine and Therapeutics, Department of Genetic Medicine and Regenerative Therapeutics, Institute of Regenerative Medicine and Biofunction, Tottori University Graduate School of Medical Science, Yonago 683-8503, Japan.

出版信息

Yonago Acta Med. 2015 Mar;58(1):15-22. Epub 2015 Mar 27.

Abstract

BACKGROUND

Epiblasts occur at the last pluripotent stage of embryonic development and are important in elucidating how the three germ layers are formed. However, little is known of the molecular mechanisms of their development. We have shown that LIM homeobox 1 (Lhx1) was involved in epiblast development in embryonic stem cells, especially meso- and endodermal differentiation. However, since epiblasts in embryoid bodies spontaneously develop into a further stage, it is difficult to study their development in this system.

METHODS

Mouse embryonal carcinoma P19 cells which have properties similar to those of epiblasts provided new avenues of investigation into the regulatory mechanism of epiblasts.

RESULTS

Overexpression of Lhx1 in P19 cells induced expression of organizer marker genes (Cer1, Gsc) and endoderm marker genes (Gata6, Foxa2, Sox17) but not extra-embryonic endoderm marker genes (Sox7 or Hnf4alpha).

CONCLUSION

This study suggested that Lhx1 overexpression caused P19 cells to differentiate into an endodermal lineage. Thus, P19 cells and their derivatives can be a useful model system to study how the three germ layers are formed.

摘要

背景

上胚层出现在胚胎发育的最后一个多能阶段,对于阐明三个胚层如何形成很重要。然而,对其发育的分子机制知之甚少。我们已经表明,LIM同源盒1(Lhx1)参与胚胎干细胞中的上胚层发育,特别是中胚层和内胚层分化。然而,由于胚状体中的上胚层会自发发育到进一步阶段,因此在这个系统中研究它们的发育很困难。

方法

具有与上胚层相似特性的小鼠胚胎癌P19细胞为研究上胚层的调控机制提供了新的研究途径。

结果

P19细胞中Lhx1的过表达诱导了组织者标记基因(Cer1、Gsc)和内胚层标记基因(Gata6、Foxa2、Sox17)的表达,但未诱导胚外内胚层标记基因(Sox7或Hnf4alpha)的表达。

结论

这项研究表明,Lhx1过表达导致P19细胞分化为内胚层谱系。因此,P19细胞及其衍生物可以成为研究三个胚层如何形成的有用模型系统。

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