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小鼠胚胎干细胞起源的遗传调控

 GCTA 2022-06-11 发布于贵州


Genetic regulation of stem cell origins in the mouse embryo.


|核心内容:

“干细胞”实际上已经成为一个家喻户晓的术语,但什么是干细胞,它从何而来?

胚胎干细胞来自于小鼠早期胚胎,即囊胚,它们分化出三种干细胞: 胚胎干细胞(ESC)、滋养层干细胞(TSC)和胚外内胚层细胞(extraembryonic endoderm, XEN)


这些干细胞似乎来源于囊胚内三个不同的组织谱系: 外胚层、营养外胚层和胚外内胚层。

了解这些谱系是如何在发育过程中产生的,将有助于理解干细胞状态的建立和维持以及限制干细胞效力的机制。

遗传学分析已经能够鉴定几个对小鼠囊胚的谱系决定很重要的基因。

其中,Oct4、 Nanog、 Cdx2和 Gata6编码三个胚泡谱系所需的转录因子,以及维持各自干细胞类型所需的转录因子。

 Precursor (totipotent)+cdx2=tsc

 Precursor (totipotent)+oct4+Gata6=xen

 Precursor (totipotent)+oct4+Nanog=epiblast


有趣的是,对其中几个因素的基因操纵可以导致这些干细胞之间的谱系转换,这表明关键谱系决定基因的知识可以帮助更广泛地控制干细胞的分化。

从人类囊胚中也分离出了多能干细胞,但这些细胞与小鼠囊胚干细胞之间的关系仍有待探索。

本文综述了胚泡形成过程中谱系分配的遗传调控,并讨论了小鼠胚胎干细胞与人胚胎干细胞的异同。

原文摘要:


'Stem cell' has practically become a household term, but what is a stem cell and where does it come from? 

Insight into these questions has come from the early mouse embryo, or blastocyst, from which three kinds of stem cells have been derived: embryonic stem (ES) cells, trophoblast stem (TS) cells, and extraembryonic endoderm (XEN) cells. 

These stem cells appear to derive from three distinct tissue lineages within the blastocyst: the epiblast, the trophectoderm, and the extraembryonic endoderm. 

Understanding how these lineages arise during development will illuminate efforts to understand the establishment and maintenance of the stem cell state and the mechanisms that restrict stem cell potency. 

Genetic analysis has enabled the identification of several genes important for lineage decisions in the mouse blastocyst. 

Among these, Oct4, Nanog, Cdx2, and Gata6 encode transcription factors required for the three lineages of the blastocyst and for the maintenance their respective stem cell types. 

Interestingly, genetic manipulation of several of these factors can cause lineage switching among these stem cells, suggesting that knowledge of key lineage-determining genes could help control differentiation of stem cells more generally. 

Pluripotent stem cells have also been isolated from the human blastocyst, but the relationship between these cells and stem cells of the mouse blastocyst remains to be explored. 

This review describes the genetic regulation of lineage allocation during blastocyst formation and discusses similarities and differences between mouse and human ES cells.




参考文献:10.1111/j.1399-0004.2005.00478.x

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